Characteristics of included studies [ordered by study ID]
Agra 1981
|
| Methods | Randomized trial of 2 4.5-month and one 3-month regimens, each with SHRZ. A regimen adding ethionamide as a 5th drug was discontinued because of high side effect rates and is not included in this review. |
|
| | Participants | 266 adults with smear- and culture-positive TB, and <15 days of previous TB treatment entered
Excluded from relapse analysis:
Pretreatment ineligibility: 34/266 (13%)
Continued drug after trial: 4/266 (2%)
Defaulted:
3RSZH: 7/62 (11.3%)
3SHRZ/1.5RH: 4/34 (11.7%)
3SHRZ/1.5SHZI: 5/54 (9.3%) |
|
| | Interventions | 1. 3SHRZ followed by 1.5 month placebo tablets
2. 3SHRZ/1.5RH
3. 3SHRZ/1.5SHZI
Daily dosages for first 3 months (all regimens):
S: 0.75 g
H: 58 mg/kg
R: 10 mg/kg
Z: 35 mg/kg
Regimen 2 daily dosage final 1.5 months:
H: 5-8 mg/kg
R: 10 mg/kg
Regimen 3 twice weekly dosage final 1.5 months:
S: 0.75 g
H: 14 mg/kgoZ: 60 mg/kg
All participants made monthly visits to the clinic and were given supplies of daily placebo tablets through 2 years after the start of the study. |
|
| | Outcomes | Sputum conversion during and immediately following treatment
Radiologic assessment at various points int ime
Relapse at 1 year (defined as a positive sputum culture in 2 consecutive months) |
|
| | Notes | More than 10% of the patients entered "defaulted" in treatment, and were not included in the analysis.
The two 4.5-month regimens are combined in the box and line diagram. |
|
|
Germany 1986
|
| Methods | Randomized trial of 1 3-month and 2 6-month regimens |
|
| | Participants | 363 patients with sputum positive TB entered
Excluded from relapse analysis:
Prerandomization ineligibility: 23/363 (6%)
Side effects: 21/363 (6%)
Protocol violations, lack of cooperation, other: 19/363 (5%) |
|
| | Interventions | 3SHRZ
6SHRZI
3SHRZ/3SHZI
Dosages: not given |
|
| | Outcomes | Bacteriologic relapse at 36-48 months after starting treatment. |
|
| | Notes | 3-month regimen stopped enrollment early because of poor results, leading to imbalance among treatment groups.
17% of enrolled patients excluded from analysis. |
|
|
Hong Kong 1979a
|
| Methods | Randomized trial of 2-, 3-, and 12-month regimens, with shorter regimens containing 4 drugs. |
|
| | Participants | 1212 adults with sputum smear negative, radiographically active TB.
691 culture negative, 381 culture positive, analyzed separately.
Excluded from relapse analysis:
Pretreatment ineligiblity: 9/1212 (1%)
Side effects: 32/691 (5%) (culture negative patients only)
Other reasons: 91/691 (13%) (culture negative patients only) |
|
| | Interventions | 2SHRZ
3SHRZ
3SPH/9SHI
Daily dosages:
S: 0.75 g
H: 300 mg
R: 450 mg
Z: 1.5 g (<50 kg), 2.0 (>50 kg)
PAS: 10 g
Intermittent (2X/week):
S: 1.0 g
H: 15 mg/kg |
|
| | Outcomes | Bacteriologic relapse 12 months after starting treatment. |
|
| | Notes | Follow-up period is shorter than other studies. |
|
|
Hong Kong 1979b
|
| Methods | — |
|
| | Participants | — |
|
| | Interventions | — |
|
| | Outcomes | — |
|
| | Notes | — |
|
|
Hong Kong 1989a
|
| Methods | Randomized trial of 4-month and 6-month regimens of 4 drugs each in sputum culture positive patients.
Randomized trial of 3-month and 4-month regimens of 4 drugs each in sputum culture negative patients. |
|
| | Participants | 2020 adults with sputum smear negative radiologically active TB. 592 sputum culture positive, 1118 sputum culture negative in analysis.
Excluded from relapse analysis:
Preadmission ineligibility: 61/2020 (3%)
Side effects: 119/2020 (6%)
Defaulted: 104/2020 (5%) |
|
| | Interventions | Patients with positive culture - 4 v 6 month; 4-month regimens were either daily (D) or intermittent (I)
4SHRZ
4SHRZI
6SHRZI
Patients with negative culture - 3 v 4 month
SHRZ3D
SHRZ3I
SHRZ4I
Daily dosages:
S: 0.75 g
H: 300 mg
R: 450 mg (<50 kg), 600 mg (>50 kg)
Z: 1.5 g (<50 kg), 2.0 g (>50 kg)
Intermittent dose (3X/week):
S: 0.75 g
H: 15 mg/kg
R: 600 mg
Z: 2.0 g (>50 kg), 2.5 g (>50 kg) |
|
| | Outcomes | Bacteriologic relapse up to 5 years after starting treatment |
|
| | Notes | For boxes and lines, the daily and intermittent regimens are combined, as the results did not differ significantly. Therefore, those groups have about twice as many individuals as the comparison. |
|
|
Hong Kong 1989b
|
| Methods | — |
|
| | Participants | — |
|
| | Interventions | — |
|
| | Outcomes | — |
|
| | Notes | — |
|
|
S. India 1983
|
| Methods | Randomized trial of 1 5-month and 2 7-month regimens. Initial phase included 4 drugs in the 5-month and 1 7-month regimen (no R in 2nd 7-month regimen). |
|
| | Participants | 509 adults with active, sputum positive TB, including 103 with drug-resistant bacilli.
Excluded from relapse analysis (drug sensitive group):
Pretreatment ineligibility: 17/509 (3%)
Died in 1st week: 4/509 (1%)
Defaulted: 13/509 (3%) (5, 4, and 4 in groups 1, 2, 3, respectively)
Excluded from relapse analysis (drug resistant group):
Pretreatment ineligibility: 0
Died of TB: 1/103 (1%)
Died other causes: 2/103 (2%) |
|
| | Interventions | 1. 2SHRZ/3SHZI
2. 2SHRZ/5SHZI
3. 2SHZ/5SHZI
In addition, patients in all 3 groups were randomized again to receive prednisolone or no prednisolone for the first two months of treatment. |
|
| | Outcomes | Bacteriological relapse at 24 months after finishing treatment (relapse after 12 months was reported only for relapses that resulted in retreatment).
Results are reported by treatment group only for patients with initially drug susceptible strains.
The results for a total of 52 patients in groups 1 and 2 are lumped together, compared with results in 46 patients (including "phase 1" and "phase 2" combined) in group 3.
Toxicity outcomes were not reported by treatment group, but according to whether or not rifampin was included in the regimen. |
|
| | Notes | |
|
|
S. India 1986
|
| Methods | Randomized trial of 1 3- and 2 5-month regimens.
The 3-month and 1 5-month regimen included 4 drugs, and the other 5-month regimen included 3 drugs (no R). |
|
| | Participants | 919 adults with sputum-positive TB. 805 in final analysis: 694 with drug-sensitive strains, 111 with resistance to 1 or more drugs.
Excluded from relapse analysis:
Pretreatment ineligibility: 43/919 (5%)
Deaths or adverse reactions: 7/919 (1%)
Defaulted: 64/919 (7%) |
|
| | Interventions | 3SHRZ
3SHRZ/2SHZ
3SHZ/2SHZ
Dosages:
1st 3 months, daily:
S: 0.75 g
H: 400 mg
R: 12 mg/kg in 3 graded doses
Z: 35 mg/kg in 5 graded doses
For 5-month regimens, last 2 months drugs 2X/week
S: 0.75 g
H: 15 mg/kg in 3 graded doses
Z: 70 mg/kg in 5 graded doses
Patient who missed doses were given added days of treatment at end of regimen to make up for loss. |
|
| | Outcomes | Bacteriologic relapse requiring treatment up to 24 months after stopping treatment. |
|
| | Notes | 5-year follow-up is reported only for Madras patients. |
|
|
Singapore 1979a
|
| Methods | Randomized trial of 2 4-month and 2 6-month regimens, each with 4 drugs in initial 2-month phase. |
|
| | Participants | 400 sputum-positive pulmonary TB patients, age 15 or more, with no previous anti-TB treatment entered.
Excluded from relapse analysis:
Pretreatment ineligibility: 12/400 (3%)
Adverse reactions: 19/400 (5%)
Given wrong drugs: 2/400 (1%)
Died: 1/400 (0%)
Defaulted: 3/400 (1%)
37 excluded for pre-treatment ineligiblity.
345 assessed at 30 months (314 with initially drug-susceptible strains and 31 resistant to at least one drug initially) |
|
| | Interventions | Daily treatment (70% of participants were outpatients), under direct observation, with the following 4 regimens:
2SHRZ/4HRZ
2SHRZ/4HR
2SHRZ/2HRZ
2SHRZ/2HR
Daily dosage:
S: 0.75g
H: 300 mg
R: 450 mg (<50 kg), 600 mg (>50 kg)
Z: 1.5 g (<50 kg), 2.0 g (>50 kg) |
|
| | Outcomes | Sputum conversion during and immediately after treatment
Bacteriologic relapse (culture positive) at 6 and 30 months and 5-8 years after start of treatment
Adverse reactions |
|
| | Notes | Includes a small number of patients in each group with bacilli resistant to H, R, or both.
All patients with sensitive bacilli were culture-negative by the end of month 3 of treatment. |
|
|
Singapore 1979b
|
| Methods | — |
|
| | Participants | — |
|
| | Interventions | — |
|
| | Outcomes | — |
|
| | Notes | — |
|
|
Characteristics of excluded studies [ordered by study ID]
|
| Study | Reason for exclusion |
|---|
| | East Africa 1978 | Randomized trial comparing 5 different 4-month (17-week) regimens. |
| | France 1976 | Randomized trial comparing two 3-month regimens: daily (HRS) vs partially intermittent (H and R 3 times/week, daily S) treatment. |
|
|
Characteristics of studies awaiting assessment [ordered by study ID]
Bock 2001
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Borisova 2003
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Gravendeel 2003
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Hernandez 1993
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Jasmer 2002
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Lwilla 2003
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Matteelli 1999
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Mawer 2001
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Sanchez 2004
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Teo 2002
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Yu 2001
|
| Methods | — |
| | Participants | — |
| | Interventions | — |
| | Outcomes | — |
| | Notes | — |
|
|
Comparison 1. 2 months vs longer
Comparison 2. 3 months vs longer
Comparison 3. 4 months vs longer
Comparison 4. 5 months vs longer
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Relapse within 12 months of finishing treatment | 1 | 390 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.24 [0.90, 5.59] |
| | 2 Toxicity requiring interruption, alteration, or cessation | 0 | 0 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
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