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Amantadine and rimantadine for influenza A in children and the elderly

  1. Márcia G Alves Galvão2,
  2. Marilene Augusta Rocha Crispino Santos2,
  3. Antonio JL Alves da Cunha1,*

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 18 JAN 2012

Assessed as up-to-date: 27 JUN 2011

DOI: 10.1002/14651858.CD002745.pub3


How to Cite

Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJL. Amantadine and rimantadine for influenza A in children and the elderly. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD002745. DOI: 10.1002/14651858.CD002745.pub3.

Author Information

  1. 1

    School of Medicine, Federal University of Rio de Janeiro, Department of Pediatrics, Rio de Janeiro, Rio de Janeiro, Brazil

  2. 2

    Municipal Secretariat of Health, Rio de Janeiro, RJ, Brazil

*Antonio JL Alves da Cunha, Department of Pediatrics, School of Medicine, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, 373, Edificio do CCS - Bloco K - 2o. andar, Sala K49, Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil. acunha@hucff.ufrj.br. antonioledo@yahoo.com.br.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 18 JAN 2012

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This is not the most recent version of the article. View current version (21 NOV 2014)

 
Characteristics of included studies [ordered by study ID]
Clover 1986b

MethodsRandomised, parallel, double-blind comparison of RMT with PB. The trial took place during an outbreak of influenza A/H1N1 in Oklahoma. Study duration: 5 weeks. Patients and providers were blinded. Outcome assessor method of blinding was unclear. Dropouts: 3 families who moved outside the study area, 1 in the placebo group whose parents attributed the 'medication' to the reducing the child's performance at school, and 1 in the RMT group due to a non-influenza illness in a 4-year-old child. Co-interventions and other potential confounders were not observed


ParticipantsThere was a total of 146 participants, including 76 children which was our subgroup of interest. Inclusion criteria: children within 35 families during a naturally occurring outbreak of influenza A. Exclusion criteria: if any family member was known to have cardiac, pulmonary, or neurologic disease; if a female family member was pregnant or actively trying to become pregnant; if any family member had received the influenza vaccine during the past year; if any member was taking medications that might interfere with the study. Gender: both females and males were included (proportion not specified). Disease stage: RMT was administered as a prophylactic when influenza A was identified within community


InterventionsRMT: 5 mg/kg/d, max: 100 mg/ d (< 10 years) or 200 mg/ d (> 10 years). Oral route. Duration: 5 weeks


OutcomesLaboratory proved infection cases and reported adverse effects


Notes1 to 18 years old


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskIt is reported that "...children...received either RMT or PB in a double-blind, random assignment". Nevertheless, randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not clearly described

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data are unlikely to be related to true outcome

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is stated that "...children...received either RMT or PB in a double-blind, random assignment", but the specific people who were blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskIt is stated that "...children...received either RMT or PB in a double-blind, random assignment", but the specific people who were blinded are not listed

Clover 1991

MethodsRandomised, parallel, comparison of RMT with PB. Multicentre trial that took place during an influenza season for 3 to 4 weeks after the start of treatment. Patients were blinded. Outcome assessor blinding was unclear. Dropouts: none (in the subgroup of interest), co-interventions and other potential confounders were not observed


ParticipantsThere was a total of 84 participants, including 46 children which was our subgroup of interest. Inclusion criteria: children within families consisting of 2 to 5 members with at least one adult (ranging in age from 18 to 75 years and one child aged between 1 to 17 years during a naturally occurring outbreak of influenza A. Exclusion criteria: participants who had a history of AMT hypersensitivity, chronic respiratory disease, severe medical illness, neuropsychiatric disorder; were pregnant or lactating; had a recently documented influenza A virus infection; required long-term drug therapy with AMT or drugs that could interfere with RMT or with clinical assessments (e.g., aspirin, tranquillizers, antihistamines and decongestants. Gender: unclear. Disease stage: all the eligible participants were given the assigned drug as soon as influenza was first recognised in family members (the index patient) and after the member had been evaluated by a study nurse


InterventionsRMT: 5 mg/kg/d, max: 150 mg/d (= or < 10 years or weighing less than 30 kg) or 200 mg/d (> 9 years who weighed more than 30 kg). Oral route. Duration: 10 days


OutcomesThe outcome of interest was laboratory proved infection cases


Notes1 to 17 years old


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors stated it was a randomised study and that randomisation is described in another article (Hayden 1989): "all eligible family members...were randomly assigned as a block to receive either RMT or PB". The method used is not described

Allocation concealment (selection bias)Low riskRandomisation was carried out in one of the centres where this multicentric trial was conducted

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data are unlikely to be related to true outcome

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAuthors stated it was a double-blinded trial as described in other article (Hayden 1989): "the study was double-blind...trial". Nevertheless, the specific people who were blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAuthors stated it was a double-blinded trial as described in other article (Hayden 1989): "the study was double-blind...trial". Nevertheless, the specific people who were blinded are not listed

Crawford 1988

MethodsRandomised, parallel, double-blind trial in which prophylactic efficacy of RMT against influenza A infection in children was evaluated. RMT was compared to PB. The trial took place during a naturally occurring outbreak of influenza A (H3N2) in Oklahoma City, USA, from November, 1984 to March, 1985. Study duration: 5 weeks. Withdrawal: 3 children in the RMT group were found post-study to have had documented influenza A infection before or on the day of institution of prophylaxis and were excluded from the analysis. 17 people from 5 families withdrew because of relocation or refusal to have a second blood specimen drawn. Their age group was not stated


ParticipantsThere was a total of 110 participants from 29 families, including 56 children which was our subgroup of interest. Inclusion criteria: children within 29 families during a naturally occurring outbreak of influenza A infection. Exclusion criteria: if any family member was known to have cardiac, pulmonary, or neurologic disease; if a female family member was pregnant or actively trying to become pregnant; if any family member had received the influenza vaccine during the past year; if any member was taking medications that might interfere with the study. Gender: both females and males were included (proportion not specified). Disease stage: RMT was administered as a prophylactic when influenza A was identified within community


InterventionsRMT: 5 mg/kg/d, max: 100 mg/d (< 10 years) or 200 mg/d (> 10 years). Oral route


OutcomesLaboratory proved infection cases. Adverse effects


Notes1 to 18 years old


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors stated it was a "... a randomised...clinical trial" although randomisation methods are not described

Allocation concealment (selection bias)Unclear riskThe authors state that their " study design has been previously reported" (Clover 1986b), but even in that trial, the method of concealment is not clearly described

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data unlikely to be related to outcome

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAuthors stated it was "a double-blind PB controlled clinical trial". Nevertheless, the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAuthors stated it was "a double-blind PB controlled clinical trial". Nevertheless, the specific people who are blinded are not listed

Finklea 1967

MethodsRandomised, parallel, double-blind, trial in which AMT use as prophylaxis in naturally-occurring acute respiratory illness. AMT was compared to PB. The trial took place between February 1965 to June 1965. The method of blinding is unclear. Study duration: 18 weeks. Withdrawal was the same for the two groups - discharge from school (19%). The proportion was not stated


ParticipantsThere were 293 participants from both sexes (proportion not stated), from 8 to 19 years of age. The participants were volunteers at a school for intellectually handicapped but educable children. Sera pairs tests were obtained in 237 children. Exclusion criteria: children receiving tranquillizers, sympathomimetic amines or anticonvulsives. Co-morbid conditions: intellectually handicapped children


InterventionsAMT: 1 to 2.5 mg/kg. (Pre-puberal: 60 mg/dose, 2 x/d, during the first week and 1 X/d during the rest of the period of the study. Older children: 100 mg/dose, 2 x/d, during the first week and 1 x/d during the rest of the period of the study


OutcomesFourfold rises in CF and/or HI tilter against A2/AA/1/65


Notes8 to 19 years old


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors stated "volunteers were assigned to AMT or the PB group by randomisation", although randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not clearly described

Incomplete outcome data (attrition bias)
All outcomes
Low riskIt is stated that "The rate of withdrawal...(the same for the two groups) was small. The reason for withdrawal was discharge from school"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAlthough it was "a double-blind study", the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAlthough the trial is described as "a double-blind study", the specific people who are blinded are not listed

Gravenstein 2005

MethodsRandomised, parallel, double-blind comparison of RMT with zanamivir. Identical PB (inhaled or tablets) were used. The trial took place in nine long-term care facilities in the United States over 3 winter seasons. Because the study was conducted over multiple influenza seasons, some participants were randomised more than once. Study duration: 3 winter seasons. Co-interventions and other potential confounders were not observed


ParticipantsThere were 231 participants in the RMT group and 226 in the zanamivir group (intent-to-treat population) of both sexes (29% female in RMT group and 30% female in zanamivir group. More than 75% of the participants were 65 years of age or older (90% in RMT group and 89% in zanamivir group)


InterventionsUpon an influenza outbreak participants were randomised (1:1) to inhaled zanamivir plus PB or inhaled PB plus zanamivir 100 mg tablets for 14 days


OutcomesThe outcome of interest was laboratory proved infection cases


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors describe the trial as "a randomised, parallel comparison of RMT with zanamivir", but randomisation methods are not described

Allocation concealment (selection bias)Unclear riskConcealment is not clearly described

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcome data are unlikely to be related to the true outcomes

Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe trial is described as a " double-blind comparison of RMT with zanamivir. Identical PB (inhaled or tablets) were used". Nevertheless, the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe trial is described as a " double-blind comparison of RMT with zanamivir. Identical PB (inhaled or tablets) were used". Nevertheless, the specific people who are blinded are not listed

Hall 1987

MethodsRandomised, parallel, double-blind comparison of RMT with acetaminophen. Study duration: 7 days. 1 patient dropped out, due to AE. Co-interventions and other potential confounders were not observed


Participants69 children were included, 40 females and 29 males. The inclusion criteria were: clinical illness and viral isolation. Exclusion criteria: previously unhealthy aged 1 to 15 years. Disease stage: clinical illness and confirmed laboratory infection


InterventionsRMT: 6.6 mg/kg/d, max: 150 mg/d (< 9 years) and 200 mg/d (>= 9 years), 2 x/d; by oral route, for 5 days


OutcomesMean symptom score of: fever, conjunctivitis, eye symptoms (pain on movement, fever up to 3rd day, conjunctivitis up to 3rd day, eyes symptoms (pain on movement and visual distortion); cough up to 7th day; malaise up to 6th day; CNS symptoms


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskIt is stated in the published study that "Patients were assigned to the RMT or acetaminophen treatment group under a double-blind, randomised allocation". The investigators also reported in their correspondence to the reviewers that computer random system was used to randomise participants

Allocation concealment (selection bias)Low riskParticipants and investigators enrolling participants could not foresee assignment because a pharmaceutical-controlled randomisation was used to conceal allocation, as stated in the authors' correspondence to the reviewers

Incomplete outcome data (attrition bias)
All outcomes
Low riskOne "child receiving RMT complained of nausea and vomiting and withdrew from the study on the second day". The proportion of missing outcomes compared with observed event risk is not enough to have a clinically relevant impact on the intervention effect estimate

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAlthough "patients were assigned to the RMT or acetaminophen treatment group under a double-blind, randomised allocation", the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAlthough "patients were assigned to the RMT or acetaminophen treatment group under a double-blind, randomised allocation", the specific people who are blinded are not listed

Kitamoto 1968

MethodsRandomised, parallel, double-blind comparison of AMT with PB. This trial took place during an outbreak of influenza in Japan. Study duration: 7 days. Patient, provider and outcome assessor method of blinding is unclear. Dropouts: none co-interventions and other potential confounders were not observed


ParticipantsThere were 355 participants. Although the proportions are not cited, it is stated that the groups are comparable in the following criteria: sex, age, influenza vaccination history, distribution and geometric mean of HI and CF titre in acute sera, interval between onset of symptoms and start of treatment, and maximum body temperature before the treatment. 158 participants of both genders met the age criteria. 91 children were cases of clinical influenza with serological confirmation The proportion of males and females was not stated. Inclusion criteria: respiratory symptoms evident within the 2nd day of illness. Disease stage: clinical symptoms within 2nd day of illness


InterventionsAMT: 50 mg/d (one to two years old); 100 mg/d (three to five years old); 150 mg/d (6 to 10 years old), by oral route, for 7 days


OutcomesFever up to 4th day. AE: nausea/ vomiting; diarrhoea; exanthema; malaise; muscular, limb pain; headache; dyspnoea; cyanosis; stimulation/insomnia; dizziness; arrhythmia


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskIt was stated that "AMT or PB was given to the patient at random" , although randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not described

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere was no missing patients, although "four cases were shown to be influenza B and were excluded from statistical analysis"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAlthough "AMT or PB was given to the patient at random by double-blind method" the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAlthough "AMT or PB was given to the patient at random by double-blind method" the specific people who are blinded are not listed

Kitamoto 1971

MethodsRandomised, parallel, double-blind comparison of AMT with PB. The trial took place during an outbreak of influenza in the winter of 1968 to 1969 in Japan. The study duration was at least seven days. Patient, provider and outcome assessor method of blinding was unclear. Dropouts were not stated. Co-interventions and other potential confounders: concomitant administration of antipyretics. It was also performed an analyses with patiens who received concomitant antipyretics


ParticipantsOf the 737 participants, 155 participants of both genders met the inclusion criteria. Although the proportions are not cited, it is stated that the groups are comparable in the following criteria: sex, age, influenza vaccination history, distribution and geometric mean of HI and CF titer in acute sera, interval between onset of symptoms and start of treatment, and maximum body temperature before the treatment. Inclusion criteria: respiratory symptoms evident within the 2nd day of illness. Disease stage: clinical symptoms within 2nd day of illness


InterventionsAMT: 50 mg/d (one to two years old); 100 mg/d (3 to 5 years old); 150 mg/d (6 to 10 years old), by oral route, for 7 days


OutcomesFever up to 4th day. AE: nausea/vomiting; diarrhoea; exanthema; malaise; muscular, limb pain; headache; stimulation/insomnia; dizziness; arrhythmia


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe author states "patients were given AMT or PB according to randomly distributed individual code of the double-blind method", although randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not described

Incomplete outcome data (attrition bias)
All outcomes
Low riskAthough there was no missing outcome data, the author states that "only patients with Hong Kong influenza in whom medication was started within 2 days" were included in statistical analysis". "In order to exclude the possible influence of concomitantly administered antipyretics on the defervescent effect of AMT the same analysis was performed with 134 Hong Kong influenza patients who had received no concomitant antipyretics"

Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe author states "patients were given AMT or PB according to randomly distributed individual code of the double-blind method". Nevertheless, the specific people who are blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe author states "patients were given AMT or PB according to randomly distributed individual code of the double-blind method". Nevertheless, the specific people who are blinded are not listed

Monto 1995

MethodsRandomised, parallel, double-blind comparison of two different dosis of RMT with PB. The trial took place during an outbreak of influenza A/H3N2 during 1993. Study duration: eight weeks. 62% withdrew because of side effects, death, discharge, hospitalisation, physician's request and refusal to continue participation. Co-interventions and other potential confounders were not observed


ParticipantsA total of 328 participants, 275 females and 53 males were included. Inclusion criteria: residents of 10 nurse homes who agreed to participate in the study. Exclusion criteria: patients with significant renal or hepatic disease. Disease stage: RMT was administered as prophylaxis


InterventionsRMT: 100 mg/d; RMT: 200 mg/d; PB. Ratio: 2:2:1 Duration: up to 8 weeks


OutcomesDeath. Adverse effects: dry mouth, drowsiness/fatigue, headache, irritability, dizziness/light headedness, nausea/vomiting, abdominal pain, body weakness or disability, confusion, depression, impaired concentration, insomnia or sleeplessness, loss of appetite, rash or allergic reaction, seizure or clonic twitching


NotesThree groups: RMT 100 AMT 200 and PB


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAlthough the authors state that the participants were randomly assigned to receive of active medication (100 or 200 mg of RMT per day) or placebo, the randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not described

Incomplete outcome data (attrition bias)
All outcomes
High riskAuthors cited that an "increased risk of withdrawal from the study only on the basis of perceived side effects was demonstrated among participants in both groups receiving active medication, especially the 200 mg/day group, compared with the placebo group; however, these associations were not statistically significant" The reasons for missing outcome data are likely to be related to true outcome

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is stated that "staff and residents were blinded to group assignment"

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo blinding is stated. The outcome is likely to be influenced by lack of blinding

Patriarca 1984

MethodsRandomised, parallel, double-blind comparison of RMT with PB. The trial took place during an outbreak of influenza A (H3N2) viruses were isolated from patients in the community. The study was conducted from early January 1983 to 6 April. Patient, provider and outcome assessor method of blinding is unclear


Participants35 participants, 68 to 102 years old, of non-specified gender, all of whom had been vaccinated the previous autumn. Inclusion criteria: residents of 3 nursing homes who agreed to participate in the study. Exclusion criteria: patients with medical conditions that might increase the severity of side effects or require careful adjustments in the dosage of RMT, which include: significant renal impairment (SCr > 2 mg/d) or liver disease, acute congestive heart failure, seizure disorders, psychosis, severe pitting oedema, orthostatic hypotension, and conditions requiring central nervous system stimulants. Disease stage: RMT was administered as prophylaxis


InterventionsRMT: 100 mg twice a day; PB. Duration: 80 (+/- 4,9) days prophylaxis


OutcomesAdverse reactions: anxiety, confusion, insomnia, anorexia, fatigue, dizziness, nausea and vomiting


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe authors stated that "participants ... were randomly assigned to receive either RMT or PB". Nevertheless, randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not described

Incomplete outcome data (attrition bias)
All outcomes
High riskIt was cited that 2 participants from the intervention group withdrew because of side effects. 1 suffered a generalised convulsion of undetermined etiology (a participant with an underlying idiopathic seizure disorder). 3 later withdrew for no described reasons. 2 participants of PB group also withdrew. Reasons for missing outcome data are likely to be related to the true outcome, with imbalance in reasons for missing data across intervention and control groups

Blinding of participants and personnel (performance bias)
All outcomes
Low riskIt is stated that "a double-blind, placebo-control trial" was conducted. Nevertheless the specific people who were blinded are not listed

Blinding of outcome assessment (detection bias)
All outcomes
Low riskIt is stated that "a double-blind, placebo-control trial" was conducted. Nevertheless the specific people who were blinded are not listed

Payler 1984

MethodsRandomised, parallel trial. Blindness is not stated. AMT use as prophylaxis in naturally-occurring acute respiratory illness. AMT was compared to no specific treatment. The trial took place in the autumn of 1982. Study duration: 14 days. Patients excluded from analysis were similar in the two groups and the reasons were: students were day boys from whom samples were not available: students infected before the start of AMT; compliance failures


ParticipantsThere were 604 randomised students and 536 were analysed. All of them were male, from 13 to 19 years of age. The participants were students of a boarding school. Once influenza A outbreak had been detected, samples were taken from all boys who were sufficiently unwell to be absent from lessons even if they did not have a fever. Nasopharyngeal aspirates were examined for viruses by rapid immunofluorescent microscopy and tissue culture. Once outbreaks had been identified, only culture methods were used


InterventionsAMT: 100 mg/ dose, 1 x/d, during the 14 days


OutcomesClinical and laboratory-proved influenza A


Notes13 to 19 years old


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskIn a correspondence to the reviewers, the author reported that the randomisation had been carried out by the statistical department of a pharmaceutical company

Allocation concealment (selection bias)Low riskParticipants and investigators enrolling participants could not foresee assignment because a pharmaceutical company-controlled randomisation was used to conceal allocation, and kept the key to the randomisation, and only when the study was analysed was the code broken, as stated in the authors' correspondence to the reviewers

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAthough there was no blinding stated, the review authors judge that the outcome is not likely to be influenced by the lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAthough there was no blinding stated, the review authors judge that the outcome is not likely to be influenced by the lack of blinding

Schilling 1998

MethodsRandomised, parallel, unblinded trial. RMT and zanamivir were compared for prophylaxis of influenza A. The trial began in November 1996. Drug administration: 14 days. Number of respiratory illness was monitored until January 1997. The participants were volunteers residents of a nursing home for veterans and their spouses. Inclusion criteria: volunteers living in a unit of the nursing home where outbreak of influenza was declared. Exclusion criteria: symptoms of new respiratory illness within the previous 7 days of the declared outbreak


Participants65 volunteers of both sexes received zanamivir and 23 rimantadine were analysed. Age range: 50 to 95 years old and 75% older than 65 years of age. The participants were volunteers residents of a nursing home for veterans and their spouses. Inclusion criteria: volunteers living in a unit of the nursing home where outbreak of influenza was declared


InterventionsRMT: 100 mg/dose, 1 x/day, during 14 days. Zanamivir: 10 mg inhaled bid and 4.4 mg intranasally bid


OutcomesClinical and laboratory proved influenza A


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe authors stated that it was a "randomised unblinded study" but randomisation method is not described

Allocation concealment (selection bias)Unclear riskConcealment is not described

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThere is Insufficient reporting of exclusions.It is stated that "six volunteers receiving zanamivir withdrew. One withdrew due to mild adverse effects" The other reasons for withdraw are not clear. It is also unclear if there were withdraws among RMT group

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAthough it was a "randomised unblinded study", the review authors judge that the outcome is not likely to be influenced by the lack of blinding

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAthough it was a "randomised unblinded study", the review authors judge that the outcome is not likely to be influenced by the lack of blinding

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

AAPCID 2007Not an RCT

Allen 2006Not an RCT

Anonymous 2006Not an RCT

Anonymous 2007Article about oseltamivir and vaccination

Aoky 1985aPharmacokinetics study of AMT and RMT

Aoky 1985bAges of participants were outside protocol age range

Aoky 1986Ages of participants were outside protocol age range

Atmar 1990Ages of participants were outside protocol age range

Baker 1969Ages of participants were outside protocol age range (participants were aged between 17 to 57 years old)

Bantia 2010Non-human trial

Barr 2007Not an RCT

Barr 2007bNot an RCT

Bauer 2007Non-human trial

Belenky 1998Ages of participants were outside protocol age range (participants were aged between 17 to 57 years old)

Bloomfield 1970Ages of participants were outside protocol age range

Boltz 2010Review article about other anti-viral drugs

Brady 1990Ages of participants were outside protocol age range

Brammer 2009Article focusing influenza surveillance

Bricaire 1990Analyses by age subgroups of interest were not available

Bryson 1990Insufficient data available

Burch 2009A systematic review about the use of other antivirals

Cady 2011Not an RCT

Callmander 1968Ages of participants were outside protocol age range (participants were 20 to 60 years old)

Carter 2008A review of the use of the influenza vaccine

Cayley 2010Article about of neuraminidase inhibitors in healthy adults,

Chawla 2009Article about strategies for pandemic preparedness

Chemaly 2006Not an RCT

Chen 2007Article about Chinese medical herbs

Cheng 2004The authors studied other antivirals, included other viral infections and ages of participants were outside protocol age range

Cheng 2009Review study with diffferent objectives

Choi 2009A trial conducted in influenza isolates

Chou 2008Article about chronic hepatitis C

Cohen 1976Ages of participants were outside protocol age range (participants were aged between 20 to 39 years old)

Cohen 2006It was a study that compared patient access to phamaceuticals in the UK and US

Cowling 2008Preliminary findings of non-pharmacetical interventions trial

Curran 2010Article about an influenza vaccine

Dawkins 1968This study assessed the prophylatic efficacy of an analogue of AMT

De la Camara 2007Review study

DeLaney 2010Review study

Denys 1963Ages of human participants were outside protocol age range (participants were aged between 19 to 21 years old). Animals were also studied

Dolamore 2003Case-control study

Dolin 1982Ages of participants were outside protocol age range (participants were aged between 18 to 45 years old)

Doyle 1998Ages of participants were outside protocol age range (participants were aged between 18 to 50 years old)

Drinevskii 1998Randomisation was not stated

Drinka 1998Groups characteristics not stated. Analyses by age subgroup of interest not available

Enger 2004Article about oseltamivir

Falagas 2010Review study

Farlow 2008Article about Alzheimers

Fiore 2008Article about Glycyrrhiza species

Furuta 2005It was a study about the mechanism of action of T-705 against influenza virus

Galabov 2006Non-human trial

Galbraith 1969aAnalyses by age subgroups of interest were not available

Galbraith 1969bOutcomes of interest were not studied

Galbraith 1971Analyses by age subgroups of interest were not available

Galbraith 1973Insufficient data available

Garman 2004Trial about drugs that inhibit the virus's neuramidase

Gerth 1966Not an RCT

Griffin 2004Pharmacological study

Guo 2007Review article

Hay 1986Study about molecular basis resistance of influenza A to amantadine

Hayden 1979Ages of participants were outside protocol age range

Hayden 1980Ages of participants were outside protocol age range

Hayden 1981Ages of participants were outside protocol age range

Hayden 1982Ages of participants were outside protocol age range

Hayden 1985Pharmacokinetics study in which ages of participants were outside protocol age range

Hayden 1986Ages of participants were outside protocol age range

Hayden 1989Analysis by age subgroups of interest was not available

Hayden 1991Analysis by age subgroups of interest was not available

Hayden 2000The drug studied was zanamivir

Hayden 2006Not an RCT

Hornick 1969Ages of participants were outside protocol age range

Hota 2007Not an RCT

Hout 2006It is a study about the human immunodeficiency virus

Hout 2006bIt is a study about the human immunodeficiency virus

Hurt 2007Not an RCT

Ilyushina 2005Not an RCT

Ilyushina 2006It was examined if the combined therapy with two classes of anti-influenza drugs could affect the emergence of resistant virus variants in vitro

Ilyushina 2007Non-human trial

Ilyushina 2007bNon-human trial

Ison 2006A case series

Ito 2000Ages of participants were outside protocol age range

Ito 2006Study about influenza vaccination

Jefferson 2006aSystematic review about antivirals for influenza in healthy adults

Jefferson 2009aSystematic review about effect and safety of AMT and RMT in healthy adults

Jones 2006A trial in which a 20-amino-acid peptide was used

Kalia 2008Article about neurological diseases

Kantor 1980Ages of participants were outside protocol age range (participants were aged between 17 to 53 years old)

Kawai 2005Not an RCT

Khakoo 1981AMT and/or RMT were not tested in this trial

Kim 2011Article about the effect of corticosteroids treatment

Kirkby 2010Article about complementary and alternative medicine. Not an RCT

Kiso 2004Descriptive study to investigate oseltamivir resistance in children treated for influenza

Kitamoto 1969Duplicated results

Knight 1969Ages of participants were outside protocol age range

Knight 1970aAges of participants were outside protocol age range

Knight 1970bAges of participants were outside protocol age range

Knight 1981Ribavirin study in which ages of participants were outside protocol age range (participants were aged between 22 to 42 years old)

Korenke 2008Article about multiple sclerosis treatment

Krylov 1978Analysis by age subgroups of interest was not available

Kulichenko 2003Ages of participants were outside protocol age range

Langlet 2009Article about the use of anti-virals for chronic hepatitis C

Le Tissier 2005Non-human trial

Leeming 1969Insufficient data available

Leone 2005Article about the use of AMT for traumatic brain injury

Leung 1979Outcomes of interest were not studied

Lim 2007A study about an influenza-like illness

Lin 2006A study about neurologic manifestations in children with influenza B

Linder 2005The authors measured the rates of antiviral and antibiotic prescribing for patients with influenza

Lipatov 2007The study was conducted in influenza viruses isolated from poultry

Little 1976Analyses by age subgroups of interest were not available

Little 1978Article is about hyperreactivity and airway dysfunction in influenza infection and not about treatment or prevention of influenza

Lutz 2005It is a study about a method for detecting and quantifying influenza A virus replication

Lynd 2005Not an RCT

Machado 2004Article was about the use of oseltamivir to control influenza complications after bone marrow transplantation

Mallia 2007Not an RCT

Maricich 2004Not an RCT

Mase 2007The study was conducted in influenza viruses isolated from poultry

Mate 1970Ages of participants were outside protocol age range

Mate 1971Ages of participants were outside protocol age range

Matheson 2007Systematic review of the use of neuraminidase inhibitors

Matsuya 2007A study about the synthesis and evaluation of dihydrofuran-fused perhydrophenanthrenes as a new anti-influenza agent

Matthews 2004Review article about treatment of viral hepatitis and oncological conditions

McCullers 2004Non-human trial

McKay 2006Non-human trial

Mishin 2005Not a clinical trial

Miyachi 2011Insufficient data available

Moffat 2008Article about biophysical aspects of the influenza virus

Monto 1979Ages of participants were outside were outside protocol age (participants were aged between 18 to 24 years old)

Morrison 2007Ages of participants were outside protoocol age range

Muldoon 1976Ages of participants were outside protocol age range

Nafta 1970A wilder range of age was considered. Analysis by age subgroups of interest was not available

Natsina 1994Randomisation was not stated. Additional information not available

Nuesch 2007Review study

O'Donoghute 1973Analysis by age subgroups of interest was not available

Obrosova-Serova 1972Study about effectiveness of midantan and interferon inducers as means of non-specific prevention of influenza

Oker-Blom 1970Ages of participants were outside protocol age range (participants were aged between 20 to 28 years old)

Ong 2007Not an RCT

Pachucki 2004Article about a diagnostic test

Peiris 2004The aim of the authors was not to study AMT and RMT to prevent or treat influenza

Pemberton 1986Article about AMT resistance in clinical influenza A and virus isolates

Petterson 1980Insufficient data available

Pritchard 1989Article about the treatment of juvenile chronic arthritis with antivirals

Quarles 1981Ages of participants were outside protocol age range

Quilligan 1966Not an RCT

Rabinovich 1969Ages of participants were outside protocol age range

Reis 2006It is an article about neurologic effects of AMT

Reuman 1989aAges of participants were outside protocol age range (participants were aged between 18 to 40 years old)

Reuman 1989bAges of participants were outside protocol age range (participants were aged between 18 to 55 years old)

Risenbrough 2005Not an RCT

Rose 1980Not an RCT

Rothberg 2005Not an RCT

Saito 2006Not an RCT

Sato 2008An article about oseltamivir treatment

Sauerbrei 2006Not an RCT

Schapira 1971Analysis by age subgroups of interest was not available

Schmidt 2004Review article

Sears 1987Ages of participants were outside protocol age range (participants were aged between 18 to 40 years old)

Semlitsch 1992The purpose of this article was to study the acute effects of AMT infusions on event-related potentials

Serkedjieva 2007Non-human trial

Shuler 2007Case-control study

Shvetsova 1974The trial authors studied different populations. No information was available about clinical outcomes and confirmation of influenza diagnosis

Simeonova 2009Non-human article

Skoner 1999Ages of participants were outside protocol age range (participants were aged between 18 to 50 years old)

Smorodintsev 1970aAges of participants were outside protocol age range

Smorodintsev 1970bAges of participants were outside protocol age range

Smorodintsev 1970cAges of participants were outside protocol age range (participants were aged between 18 to 30 years old)

Somani 1991Randomisation was not stated. The groups were not similar at baseline

Tajima 2006It is a study about etiology and treatment in hospitalised children with pneumonia

Takemura 2005Not a study about influenza A

Tappenden 2009Systematic review

Terabayashi 2006The article is about the inhibition of influenza-virus-induced cytopathy by sialyglycoconjugates

Thomas 2008Article about multiple sclerosis

Thompson 1987Insufficient data presented

Togo 1968Ages of participants were outside protocol age range

Togo 1970Ages of participants were outside protocol age range

Togo 1972The drug studied was cyclooctylamine

Townsend 2006Not an RCT

Van der Wouden 2005Not an RCT

Van Voris 1981Ages of participants were outside protocol age range

Van Voris 1985Study about four antibody techniques to assess influenza infection

Wailoo 2008Article about the use of neuraminidase inhibitors in adults

Webster 1986Non-human trial

Welton 2008Not an RCT

Wendel 1966Ages of participants were outside protocol age range (participants were aged between 17 to 54 years old)

Whitley 2007Not an RCT

Wingfield 1969Ages of participants were outside protocol age range

Wong 2006Not an RCT

Wright 1976Analysis by age subgroups of interest was not available

Wultzler 2004Not a clinical trial

Yamaura 2003The studied antiviral was oseltamivir

Younkin 1983Ages of participants were outside protocol age range (participants were aged between 17 to 20 years old)

Yuen 2005Not an RCT

Zeuzem 1999The purpose of the authors was to study treatment for chronic hepatitis C

 
Comparison 1. AMT and RMT compared to control in the treatment of influenza A in children

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Fever day 33173Risk Ratio (M-H, Random, 95% CI)0.39 [0.20, 0.79]

    1.1 AMT
2104Risk Ratio (M-H, Random, 95% CI)0.37 [0.08, 1.75]

    1.2 RMT
169Risk Ratio (M-H, Random, 95% CI)0.36 [0.14, 0.91]

 2 Cough day 7169Risk Ratio (M-H, Random, 95% CI)0.83 [0.63, 1.10]

    2.1 RMT
169Risk Ratio (M-H, Random, 95% CI)0.83 [0.63, 1.10]

 3 Malaise day 6169Risk Ratio (M-H, Random, 95% CI)1.04 [0.63, 1.70]

    3.1 RMT
169Risk Ratio (M-H, Random, 95% CI)1.04 [0.63, 1.70]

 4 Conjunctivitis day 5169Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 3.49]

    4.1 RMT
169Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 3.49]

 5 Eye symptoms day 5 (pain on movement and visual distortion)169Risk Ratio (M-H, Random, 95% CI)0.58 [0.10, 3.24]

    5.1 RMT
169Risk Ratio (M-H, Random, 95% CI)0.58 [0.10, 3.24]

 
Comparison 2. AMT and RMT compared to control in the prophylaxis of influenza A in children

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Infection5951Risk Ratio (M-H, Random, 95% CI)0.25 [0.09, 0.66]

    1.1 AMT
2773Risk Ratio (M-H, Random, 95% CI)0.11 [0.04, 0.30]

    1.2 RMT
3178Risk Ratio (M-H, Random, 95% CI)0.49 [0.21, 1.15]

 
Comparison 3. Adverse effects of AMT and RMT compared to control in children

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Diarrhoea3655Risk Ratio (M-H, Random, 95% CI)0.79 [0.42, 1.47]

    1.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.81 [0.43, 1.53]

    1.2 RMT
156Risk Ratio (M-H, Random, 95% CI)0.36 [0.02, 8.41]

 2 Exanthema2599Risk Ratio (M-H, Random, 95% CI)0.69 [0.21, 2.34]

    2.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.69 [0.21, 2.34]

 3 Malaise2599Risk Ratio (M-H, Random, 95% CI)0.89 [0.41, 1.96]

    3.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.89 [0.41, 1.96]

 4 Muscular, limb pain2599Risk Ratio (M-H, Random, 95% CI)0.85 [0.46, 1.59]

    4.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.85 [0.46, 1.59]

 5 Headache2599Risk Ratio (M-H, Random, 95% CI)0.73 [0.52, 1.03]

    5.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.73 [0.52, 1.03]

 6 Dyspnoea1159Risk Ratio (M-H, Random, 95% CI)0.37 [0.02, 9.02]

    6.1 AMT
1159Risk Ratio (M-H, Random, 95% CI)0.37 [0.02, 9.02]

 7 Gastrointestinal symptoms176Risk Ratio (M-H, Random, 95% CI)1.17 [0.08, 18.05]

    7.1 RMT
176Risk Ratio (M-H, Random, 95% CI)1.17 [0.08, 18.05]

 8 Dizziness3655Risk Ratio (M-H, Random, 95% CI)4.69 [0.53, 41.75]

    8.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)6.63 [0.32, 137.33]

    8.2 RMT
156Risk Ratio (M-H, Random, 95% CI)3.21 [0.14, 75.68]

 9 Central nervous system symptoms176Risk Ratio (M-H, Random, 95% CI)0.23 [0.01, 4.70]

    9.1 RMT
176Risk Ratio (M-H, Random, 95% CI)0.23 [0.01, 4.70]

 10 Change in behaviour176Risk Ratio (M-H, Random, 95% CI)0.23 [0.01, 4.70]

    10.1 RMT
176Risk Ratio (M-H, Random, 95% CI)0.23 [0.01, 4.70]

 11 Stimulation/insomnia2599Risk Ratio (M-H, Random, 95% CI)0.46 [0.12, 1.74]

    11.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.46 [0.12, 1.74]

 12 Cerebelar ataxia169Risk Ratio (M-H, Random, 95% CI)2.61 [0.11, 61.80]

    12.1 RMT
169Risk Ratio (M-H, Random, 95% CI)2.61 [0.11, 61.80]

 13 Hyperreactivity156Risk Ratio (M-H, Random, 95% CI)0.36 [0.02, 8.41]

    13.1 RMT
156Risk Ratio (M-H, Random, 95% CI)0.36 [0.02, 8.41]

 14 Tinnitus156Risk Ratio (M-H, Random, 95% CI)3.21 [0.14, 75.68]

    14.1 RMT
156Risk Ratio (M-H, Random, 95% CI)3.21 [0.14, 75.68]

 15 Nausea/vomiting4724Risk Ratio (M-H, Random, 95% CI)0.61 [0.24, 1.58]

    15.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.54 [0.15, 2.00]

    15.2 RMT
2125Risk Ratio (M-H, Random, 95% CI)0.96 [0.10, 9.01]

 16 Arrythmia2599Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    16.1 AMT
2599Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. AMT and RMT compared to control in the prophylaxis of influenza A in the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 RMT (proved and clinical infection)3191Risk Ratio (M-H, Random, 95% CI)0.74 [0.13, 4.07]

 2 RMT 200275Risk Ratio (M-H, Random, 95% CI)0.44 [0.12, 1.63]

 3 RMT 1002130Risk Ratio (M-H, Random, 95% CI)1.42 [0.10, 21.10]

 4 RMT Monto (100 + 200) and Patriarca2103Risk Ratio (M-H, Random, 95% CI)0.45 [0.14, 1.41]

 
Comparison 5. Adverse effects of AMT and RMT compared to control in the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Headache1198Risk Ratio (M-H, Random, 95% CI)0.83 [0.21, 3.38]

    1.1 RMT
1198Risk Ratio (M-H, Random, 95% CI)0.83 [0.21, 3.38]

 2 Stimulation/insomnia2233Risk Ratio (M-H, Random, 95% CI)1.61 [0.43, 6.02]

    2.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)1.61 [0.43, 6.02]

 3 Dizziness135Risk Ratio (M-H, Random, 95% CI)0.94 [0.15, 5.97]

    3.1 RMT
135Risk Ratio (M-H, Random, 95% CI)0.94 [0.15, 5.97]

 4 Anxiety135Risk Ratio (M-H, Random, 95% CI)2.83 [0.92, 8.74]

    4.1 RMT
135Risk Ratio (M-H, Random, 95% CI)2.83 [0.92, 8.74]

 5 Confusion2233Risk Ratio (M-H, Random, 95% CI)0.79 [0.40, 1.56]

    5.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)0.79 [0.40, 1.56]

 6 Fatigue2233Risk Ratio (M-H, Random, 95% CI)0.81 [0.41, 1.60]

    6.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)0.81 [0.41, 1.60]

 7 Nausea2233Risk Ratio (M-H, Random, 95% CI)1.99 [0.45, 8.75]

    7.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)1.99 [0.45, 8.75]

 8 Depression2233Risk Ratio (M-H, Random, 95% CI)1.63 [0.53, 4.98]

    8.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)1.63 [0.53, 4.98]

 9 Impaired concentration1198Risk Ratio (M-H, Random, 95% CI)0.5 [0.10, 2.41]

    9.1 RMT
1198Risk Ratio (M-H, Random, 95% CI)0.5 [0.10, 2.41]

 10 Loss of appetite2233Risk Ratio (M-H, Random, 95% CI)1.11 [0.56, 2.17]

    10.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)1.11 [0.56, 2.17]

 11 Rash or allergic reaction1198Risk Ratio (M-H, Random, 95% CI)3.53 [0.18, 67.28]

    11.1 RMT
1198Risk Ratio (M-H, Random, 95% CI)3.53 [0.18, 67.28]

 12 Seizures or clonic twitching1198Risk Ratio (M-H, Random, 95% CI)2.0 [0.23, 17.54]

    12.1 RMT
1198Risk Ratio (M-H, Random, 95% CI)2.0 [0.23, 17.54]

 13 Dry mouth1198Risk Ratio (M-H, Random, 95% CI)0.7 [0.23, 2.12]

    13.1 RMT
1198Risk Ratio (M-H, Random, 95% CI)0.7 [0.23, 2.12]

 14 Vomiting2233Risk Ratio (M-H, Random, 95% CI)0.99 [0.38, 2.60]

    14.1 RMT
2233Risk Ratio (M-H, Random, 95% CI)0.99 [0.38, 2.60]

 
Comparison 6. Use of different doses of AMT and RMT for prophylaxis and treatment of influenza A in the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical and laboratorial infection154Risk Ratio (M-H, Random, 95% CI)0.93 [0.21, 4.20]

    1.1 RMT
154Risk Ratio (M-H, Random, 95% CI)0.93 [0.21, 4.20]

 
Comparison 7. Adverse effects related to different doses of AMT and RMT in the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Confusion1262Risk Ratio (M-H, Random, 95% CI)0.83 [0.41, 1.65]

    1.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.83 [0.41, 1.65]

 2 Depression1262Risk Ratio (M-H, Random, 95% CI)0.44 [0.12, 1.65]

    2.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.44 [0.12, 1.65]

 3 Impaired concentration1262Risk Ratio (M-H, Random, 95% CI)0.68 [0.11, 3.98]

    3.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.68 [0.11, 3.98]

 4 Insomnia or sleeplessness1262Risk Ratio (M-H, Random, 95% CI)1.02 [0.26, 3.97]

    4.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)1.02 [0.26, 3.97]

 5 Loss of appetite1262Risk Ratio (M-H, Random, 95% CI)0.62 [0.27, 1.46]

    5.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.62 [0.27, 1.46]

 6 Rash or allergic reaction1262Risk Ratio (M-H, Random, 95% CI)0.34 [0.04, 3.21]

    6.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.34 [0.04, 3.21]

 7 Seizure or clonic twitching1262Risk Ratio (M-H, Random, 95% CI)0.11 [0.01, 2.07]

    7.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.11 [0.01, 2.07]

 8 Dry mouth1262Risk Ratio (M-H, Random, 95% CI)1.16 [0.43, 3.11]

    8.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)1.16 [0.43, 3.11]

 9 Fatigue and drowsiness1262Risk Ratio (M-H, Random, 95% CI)1.14 [0.45, 2.87]

    9.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)1.14 [0.45, 2.87]

 10 Headache1262Risk Ratio (M-H, Random, 95% CI)1.02 [0.30, 3.42]

    10.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)1.02 [0.30, 3.42]

 11 Body weakness or debility1262Risk Ratio (M-H, Random, 95% CI)0.91 [0.38, 2.18]

    11.1 RMT
1262Risk Ratio (M-H, Random, 95% CI)0.91 [0.38, 2.18]

 
Comparison 8. AMT and RMT compared to other antivirals in the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 RMT and zanamivir2545Risk Ratio (M-H, Random, 95% CI)4.63 [1.46, 14.72]

 
Comparison 9. Additional comparison: RMT compared to control in the prophylaxis of influenza A in children and the elderly

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Infection5281Risk Ratio (M-H, Random, 95% CI)0.49 [0.27, 0.92]

    1.1 RMT
5281Risk Ratio (M-H, Random, 95% CI)0.49 [0.27, 0.92]

 
Summary of findings for the main comparison.

Amantadine compared with placebo for prevention and treatment of influenza A in children

Patient or population: children with no influenza A infection (prevention) or with influenza a (treatment)

Settings: all

Intervention: amantadine

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlAmantadine

Cases of influenza A during prophylaxis

(follow up:14 to 18 weeks)
Medium risk populationRR 0.11 (0.04 to 0.3)773
(2])
⊕⊕⊝⊝
low1,2

10 per 1001 per 100
(0 to 3)

Fever after initiation of treatment

(follow-up: 3 days)
Medium risk populationRR 0.37 (0.08 to 1.75)104
(2)
⊕⊕⊝⊝
low3,4

23 per 1009 per 100
(2 to 40)

Cough after initiation of treatmentSee commentSee commentNot estimable0

(0)
See commentNo selected trial

Dizziness

(follow-up: 7 days)
Medium risk populationRR 6.63 (0.32 to 137.33)599
(2)
⊕⊝⊝⊝
very low3,4

0 per 1000 per 100
(0 to 0)

Nausea/ vomiting

(follow-up: 7 days)
Medium risk populationRR 0.54 (0.15 to 2)599
(2)
⊕⊝⊝⊝
very low3,4,5

13 per 1007 per 100
(2 to 27)

Stimulation/ insomnia

(follow-up: 7 days)
Medium risk populationRR 0.46 (0.12 to 1.74)599
(2)
⊕⊕⊝⊝
low3,4

3 per 1007 per 100
(2 to 27)

CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

 *The basis for the assumed risk (e.g. median control group risk across studies) was calculated on the basis of control event rate. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
1Allocation concealment not used or unclear.
2Sparse data.
3Allocation concealment unclear.
4Sparse data, confidence intervals do not rule out potential for null effect or harm.
5High heterogeneity unexplained.
 
Summary of findings 2.

Rimantadine compared with placebo for prevention and treatment of influenza A in children

Patient or population: children with no influenza A infection (prevention) or with influenza a (treatment)

Settings: any

Intervention: rimantadine

Comparison: control (placebo or acetaminophen)

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlRimantadine

Cases of influenza A during prophylaxis (follow-up: 1 to 35 days)Medium risk populationRR 0.49 (0.21 to 1.15)178
(3)
⊕⊕⊝⊝
low1,2

24 per 10012 per 100
(5 to28)

Fever after initiation of treatment

(follow-up: 3 days)
Medium risk populationRR 0.36 (0.14 to 0.91)69
(1)
⊕⊕⊕⊝
moderate2

38 per 10014 per 100
(5 to 34)

Cough after initiation of treatment

(follow-up: 7 days)
Medium risk populationRR 0.83 (0.63 to 1.1)69
(1)
⊕⊕⊕⊝
moderate2

81 per 10067 per 100
(51 to 89)

Dizziness

(follow-up: 35 days)
Medium risk populationRR 3.21 (0.14 to 75.68)56
(1)
⊕⊝⊝⊝
very low1,2

0 per 1000 per 100
(0 to 0)

Nausea/vomiting

(follow-up: 7-35 days)
Medium risk populationRR 0.96 (0.1 to 9.01)125
(2)
⊕⊕⊝⊝
low2

2 per 1002 per 100
(0 to 15)

Stimulation/insomniaSee commentSee commentNot estimable0
(0)
See commentNo selected trial

CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

 *The basis for the assumed risk (e.g. median control group risk across studies) was calculated on the basis of control event rate. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
1Allocation concealment unclear.
2Sparse data and confidence intervals do not rule out the potential for no effect or harm
 
Summary of findings 3.

Amantadine compared with placebo for prevention and treatment of influenza A in the elderly

Patient or population: elderly people with no influenza A infection (prevention) or with influenza a (treatment)

Settings: any

Intervention: amantadine

Comparison: control

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlAmantadine

Cases of influenza A during prophylaxisSee commentNot estimable0
(0)
See commentNo selected trial






Fever after initiation of treatmentSee commentNot estimable0
(0)
See commentNo selected trial






Cough after initiation of treatmentSee commentNot estimable0
(0)
See commentNo selected trial






DizzinessSee commentNot estimable0
(0)
See commentNo selected trial






NauseaSee commentNot estimable0
(0)
See commentNo selected trial






VomitingSee commentNot estimable0
(0)
See commentNo selected trial






Stimulation/insomniaSee commentNot estimable0
(0)
See commentNo selected trial

 
Summary of findings 4.

Rimantadine compared with placebo for prevention and treatment of influenza A in the elderly


Patient or population: elderly people with no influenza A infection (prevention) or with influenza a (treatment)

Settings: any

Intervention: rimantadine

Comparison: placebo


OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments


Assumed riskCorresponding risk

ControlRimantadine

Cases of influenza A during prophylaxisMedium risk populationRR 0.45 (0.14 to 1.41)103
(2)
⊕⊝⊝⊝
very low1,2


17per 1007 per 100
(2 to 23)

Fever after initiation of treatmentSee comment0
(0)
See commentSee commentNo selected trial







Cough after initiation of treatmentSee comment0
(0)
See commentSee commentNo selected trial







Dizziness

(follow-up: 12 weeks)
Medium risk population






12 per 10011 per 100 (2 to 70)RR 0.94
(0.15 to 5.97)
35

(1)
⊕⊕⊝⊝
low2,3

Nausea

(follow-up: 8 to 12 weeks)
Medium risk populationRR 1.99 (0.45 to 8.75)233
(2)
⊕⊝⊝⊝
very low1,2,4


8 per 10015 per 100
(3 to 66)

Vomiting

(follow-up: 8 to 12 weeks)
Medium risk populationRR 0.99 (0.38 to 2.6)233
(2)
⊕⊕⊝⊝
low1,2


7 per 1007 per 100
(3 to 17)

Stimulation/insomnia (follow-up: 8 to 12 weeks)Medium risk populationRR 1.61 (0.43 to 6.02)233
(2)
⊕⊕⊝⊝
low1,2


7 per 10011 per 100
(3 to 40)

CI: confidence interval; RR: risk ratio


GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

 *The basis for the assumed risk (e.g. median control group risk across studies) was calculated on the basis of control event rate. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
1Allocation concealment unclear and 1 study had high withdrawal rate.
2Sparse data and confidence interval do not rule out no effect or harm.
3 Allocation concealment unclear
4High heterogeneity unexplained.