Characteristics of included studies [ordered by study ID]
Zar 2007
|
| Methods | 277 individuals randomised by variable blocked randomisation lists prepared by study statistician. Randomisation was stratified for site and previous cotrimoxazole usage. Blinding:study investigator, providers, participants. |
|
| | Participants | HIV infected children attending two tertiary healthcare centres in Cape Town, South Africa.
Inclusion criteria:
Age>8weeks
Weight>2.5kg
Access to transport
Informed written consent from parent or legal guardian
Exclusion criteria:
Chronic diarrhoea
Current use of or need for INH prophylaxis
Previous hypersensitivity to INH or sulphur containing drugs
Haemoglobin < 70g/l
Neutorphil count <400cell/ul
Platelet count <50 000 x10/l
Non reversible renal failure |
|
| | Interventions | Intervention: Isoniazid (100mg tablets)
Dose: 10mg/kg/dose with a variablity of 8-12mg/kg depending on whether a quarter or half tablet were required
Frequency: Randomised to daily or three days a week Monday, Wednesday and Friday
Control: Placebo tablets identicle in appearance to Isoniazid tablets
Frequency: Randomised to daily or three days a week, Monday, Wednesday and Friday
Cotrimoxazole (5mg/kg/dose of the trimethoprim component): Given to all children <12months and those older with clinical CDC category B or C disease, in those with severe immunological impairment (CD4 count of <15% of total lymphocyte count), or in those with previous episode of Pneumocystis jirovecii pneumonia.
Frequency: according to daily or three times a week as per randomisation
Duration: Study was planned to run for 2 years however the placebo arm was terminated early on the recommendation of the data safety monitoring board (DSMB) on the basis of the results of interim analyses. |
|
| | Outcomes | Primary outcome:
Mortality
Secondary outcomes:
Incidence of confirmed or probable Tuberculosis |
|
| | Notes | Adverse events were graded 1 to 4 according to the toxicity criteria of the National Institutes of Health's division of AIDS (DAIDS). Grade 3 and 4 events were reported. |
|
| | Risk of bias |
| | Item | Authors' judgement | Description |
| | Allocation concealment? | Yes | A - Adequate |
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Characteristics of ongoing studies [ordered by study ID]
Madhi
|
| Trial name or title | A Randomized, Double Blind, Placebo Controlled Trial to Determine the Efficacy of Isoniazid (INH) in Preventing Tuberculosis Disease and Latent Tuberculosis Infection Among Infants With Perinatal Exposure to HIV |
| | Methods | |
| | Participants | Ages: 91 Days to 120 Days
Inclusion Criteria:
Mother is HIV infected. Hard copy documentation of the mother's HIV infection is unnecessary if a positive DNA PCR from her infant is available.
Received Bacille Calmette-Guerin (BCG) vaccine up to and including the 30th day of life and at least 90 days prior to study entry
Able to complete all study requirements
Normal truncated Denver Developmental Test for peripheral neuropathy at study entry
Normal deep tendon reflexes and muscle bulk, tone, and strength at study entry
Plan to live in the study area for at least 4 years
Exclusion Criteria:
Previous diagnosis of TB infection
Previous receipt of INH
Contact with a known acid fast bacilli (AFB) sputum smear or culture-positive case of TB before study entry
Current acute or recurrent (3 or more prior episodes) lower respiratory tract disease
Chronic persistent diarrhea
Significant drop in weight or failure to gain weight appropriately during a 2- to 3-month period
Contraindications for use of INH or SMX/TMP
Require certain medications
Known or suspected immune system diseases other than HIV
Current or previous diagnosis of or treatment for cancer
Current immunosuppressive therapy greater than 1 mg/kg/day of prednisone or equivalent
Anticipated long-term oral or intravenous corticosteroid therapy (greater than 3 weeks). Those receiving nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded.
Grade 3 or greater AST/SGOT, ALT/SGPT, ANC, hemoglobin, platelet count, rash, neuropathy, or myopathy at screening
Any Grade 4 clinical or laboratory toxicity within 14 days prior to study entry
Other acute or chronic conditions that, in the opinion of the investigator, may interfere with the study |
| | Interventions | Isoniazid and cotrimoxazole versus placebo and cotrimoxazole |
| | Outcomes | Primary Outcome Measures:
Time from randomization to development of tuberculosis (TB) disease or death among HIV infected children [ Time Frame: At Week 96 ]
Time from randomization to development of TB infection or death among perinatally exposed, HIV uninfected children [ Time Frame: At Week 96 ]
Secondary Outcome Measures:
Time from randomization to development of TB infection, and time from randomization to development of TB disease among HIV infected and perinatally exposed, HIV uninfected children [ Time Frame: At Week 96 and Week 192 ]
Time from randomization to death among HIV infected and perinatally exposed, HIV uninfected children [ Time Frame: At Week 96 and Week 192 ]
Population pharmacokinetics (PK) model of isoniazid (INH) among HIV infected and perinatally exposed, HIV uninfected children at two dosing interval time points on two separate occasions (at Cape Town and Durban only) [ Time Frame: Throughout study ]
Time from randomization to development of TB infection among HIV infected children [ Time Frame: At Week 96 ]
Time from randomization to AIDS-defining illness or death among HIV infected children [ Time Frame: At Week 96 and Week 192 ]
Time from randomization to development of TB disease among perinatally exposed, HIV uninfected children [ Time Frame: At Week 96 ]
Time from randomization to new first Grade 3 or higher sign or symptom [ Time Frame: Throughout study ] |
| | Starting date | March 2006 |
| | Contact information | Shabir Madhi, MD University of the Witwatersrand
George McSherry, MD UMD - New Jersey Medical School
Charles D. Mitchell, MD University of Miami |
| | Notes | Alternative ID: PACTG1041
Currently recruiting
Clinical trial registry ID:
NCT00080119 |
|
|
Zar
|
| Trial name or title | Isoniazid prophylaxis with concomitant cotrimoxazole in HIV-infected children |
| | Methods | |
| | Participants | Age: 8 weeks to 15 years
Inclusion Criteria:
HIV-infected children
Resident in Cape Town
Informed consent obtainable
weight > 2.5kg
Access to transport
HAART use for not less than 2 months but not more than 12 months with no significant demonstrated toxicity and good adherence |
| | Interventions | Isoniazid versus placebo
Cotrimoxazole
Both either three times a week or daily |
| | Outcomes | Primary Outcome Measures:
TB incidence
mortality
Secondary Outcome Measures:
intercurrent infections
adherence
adverse events
antimicrobial resistance |
| | Starting date | Jan 2003 |
| | Contact information | Heather J Zar, MD PhD 27216585350 hzar@ich.uct.ac.za
Contact: Mark Cotton, MD PhD 27219384219 mcot@sun.ac.za |
| | Notes | Currently recruiting
Clinical trial registry ID:
NCT00330304 |
|
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Comparison 1. Isoniazid versus placebo
Table 1. Search Strategy MEDLINE
|
| Search | Most recent queries |
| | #6 | Search #1 AND #2 AND #3 AND #4 Limits: Publication Date from 1980 to 2007 |
| | #5 | Search #1 AND #2 AND #3 AND #4 |
| | #4 | Search PREVENTIVE THERAPY OR CHEMOPROPHYLAXIS OR PROPHYLAXIS |
| | #3 | Search TUBERCULOSIS OR TB |
| | #2 | Search randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR ( placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp] OR comparative study [mh] OR evaluation studies [mh] OR follow-up studies [mh] OR prospective studies [mh] OR control* [tw] OR prospectiv* [tw] OR volunteer* [tw]) NOT (animals [mh] NOT human [mh]) |
| | #1 | Search HIV Infections[MeSH] OR HIV[MeSH] OR hiv[tw] OR hiv-1*[tw] OR hiv-2*[tw] OR hiv1[tw] OR hiv2[tw] OR hiv infect*[tw] OR human immunodeficiency virus[tw] OR human immunedeficiency virus[tw] OR human immuno-deficiency virus[tw] OR human immune-deficiency virus[tw] OR ((human immun*) AND (deficiency virus[tw])) OR acquired immunodeficiency syndrome[tw] OR acquired immunedeficiency syndrome[tw] OR acquired immuno-deficiency syndrome[tw] OR acquired immune-deficiency syndrome[tw] OR ((acquired immun*) AND (deficiency syndrome[tw])) OR "sexually transmitted diseases, viral"[MESH:NoExp] |
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