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Study flow diagram.
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Figure 1

Study flow diagram.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.
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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Forest plot of comparison: 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, outcome: 1.3 Relapse: sensitivity analysis accounting for missing data.
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Figure 4

Forest plot of comparison: 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, outcome: 1.3 Relapse: sensitivity analysis accounting for missing data.

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Forest plot of comparison: 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, outcome: 2.2 Relapse: sensitivity analysis accounting for missing data.
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Figure 5

Forest plot of comparison: 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, outcome: 2.2 Relapse: sensitivity analysis accounting for missing data.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 1 Relapse.
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Analysis 1.1

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 1 Relapse.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 2 Relapse: subgroup analysis.
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Analysis 1.2

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 2 Relapse: subgroup analysis.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 3 Relapse: sensitivity analysis accounting for missing data.
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Analysis 1.3

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 3 Relapse: sensitivity analysis accounting for missing data.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 4 Death from any cause.
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Analysis 1.4

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 4 Death from any cause.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 5 Treatment discontinuation.
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Analysis 1.5

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 5 Treatment discontinuation.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 6 Positive sputum culture/smear at 8 weeks.
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Analysis 1.6

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 6 Positive sputum culture/smear at 8 weeks.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 7 Treatment failure.
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Analysis 1.7

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 7 Treatment failure.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 8 Acquired drug resistance.
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Analysis 1.8

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 8 Acquired drug resistance.

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Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 9 Serious adverse events.
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Analysis 1.9

Comparison 1 Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 9 Serious adverse events.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 1 Relapse.
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Analysis 2.1

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 1 Relapse.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 2 Relapse: sensitivity analysis accounting for missing data.
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Analysis 2.2

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 2 Relapse: sensitivity analysis accounting for missing data.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 3 Death from any cause.
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Analysis 2.3

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 3 Death from any cause.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 4 Treatment discontinuation.
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Analysis 2.4

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 4 Treatment discontinuation.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 5 Positive sputum culture at 8 weeks.
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Analysis 2.5

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 5 Positive sputum culture at 8 weeks.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 6 Treatment failure.
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Analysis 2.6

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 6 Treatment failure.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 7 Acquired drug resistance.
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Analysis 2.7

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 7 Acquired drug resistance.

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Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 8 Serious adverse events.
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Analysis 2.8

Comparison 2 Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens, Outcome 8 Serious adverse events.

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Summary of findings for the main comparison. Moxifloxacin‐containing 4‐month ATT regimens versus standard 6‐month ATT regimen for drug‐sensitive pulmonary tuberculosis

Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimen for drug‐sensitive pulmonary tuberculosis

Patient or population: adults with drug‐sensitive pulmonary tuberculosis
Setting: low‐ and middle‐income countries in Africa, Asia, and Latin America
Intervention: moxifloxacin‐containing 4‐month ATT
Comparison: standard 6‐month ATT

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect

(95% CI)

Number of participants (studies)

Certainty of the evidence (GRADE)

Comments

Risk with 6‐month standard ATT

Risk with 4‐month moxifloxacin‐containing ATT

Relapse
Follow‐up: range 12 to 24 months

32 per 1000

82 more relapses per 1000
(44 more to 140 more)

RR 3.56
(2.37 to 5.37)

2265
(3 RCTs)

⊕⊕⊕⊝
MODERATEa,b,c

Due to indirectness

The 4‐month regimen probably increases relapse compared to the 6‐month regimen

Death from any cause

Follow‐up: range 18 to 24 months

21 per 1000

2 more deaths per 1000
(7 fewer to 16 more)

RR 1.06
(0.65 to 1.75)

2760
(3 RCTs)

⊕⊕⊕⊝
MODERATEa,c,d

Due to indirectness

The 4‐month regimen probably makes little or no difference in death from any cause compared to the 6‐month regimen

Treatment failure

16 per 1000

5 fewer treatment failures per 1000
(11 fewer to 8 more)

RR 0.71
(0.33 to 1.52)

2282
(3 RCTs)

⊕⊕⊕⊝
MODERATEa,c,d

Due to indirectness

The 4‐month regimen probably results in little or no difference in treatment failure compared to the 6‐month regimen

Acquired drug resistance

7 per 1000

5 fewer with acquired drug resistance per 1000

(6 fewer to 2 more)

RR 0.33
(0.08 to 1.31)

2282

(3 RCTs)e

⊕⊕⊝⊝
LOWc,f,g

Due to indirectness and imprecision

The 4‐month regimen may be little or no different than the 6‐month regimen in the incidence of acquired drug resistance

Serious adverse events

Follow‐up: range 18 to 24 months

62 per 1000

2 fewer with serious adverse events per 1000
(16 fewer to 16 more)

RR 0.97
(0.74 to 1.27)

3548
(4 RCTs)g

⊕⊕⊕⊝
MODERATEa,c,d,h

Due to indirectness

The 4‐month regimen probably results in little or no difference in serious adverse events compared to the 6‐month regimen

*The risk in the intervention group (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).
ATT: anti‐tuberculosis treatment; CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence.
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aNo serious risk of bias: although Jawahar 2013 was at high risk of allocation bias, exclusion of this trial from the sensitivity analysis did not change the direction of effect. Not downgraded.
bNo serious inconsistency: although trial results indicated a moderate degree of heterogeneity (I² = 58%), the differences were between small and large effects favouring 6‐month ATT. Changing the model from fixed effect to random effects did not alter the direction of effect. Not downgraded.
cDowngraded one level for serious indirectness: trials excluded children and adolescents, people with diabetes, and other physical comorbid conditions.
dNo serious imprecision: the 95% CI for the risk ratio was wide but event rates were low and the sample size was large; the risk ratio and the 95% CI around absolute estimates did not indicate clinically appreciable differences with either regimen. Not downgraded.
eNo serious imprecision: the 95% CI for the risk ratio was wide but event rates were low and the sample size was large; the 95% CI for the risk ratio (RR 0.5% fewer with the 4‐month regimen, 95% CI 1.1% fewer to 0.8% more) did not indicate that there were clinically important differences in proportions with treatment failure. Not downgraded.
fDrug resistance was assessed using LJ solid media in one trial, MGIT liquid media in another trial, and either or both in the third trial.
gSerious imprecision: events were few and the 95% CI for the pooled estimate was wide. In the largest study that also reported the most events, results were equivocal for acquired resistance and only possible resistance was reported. Downgraded one level.
hThree trials provided data for all outcomes in this summary table (Gillespie 2014; Jawahar 2013; Jindani 2014); Velayutham 2014 provided data only for serious adverse events.

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Summary of findings for the main comparison. Moxifloxacin‐containing 4‐month ATT regimens versus standard 6‐month ATT regimen for drug‐sensitive pulmonary tuberculosis
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Summary of findings 2. Gatifloxacin‐containing 4‐month ATT regimens compared to standard 6‐month ATT regimens for drug‐sensitive pulmonary tuberculosis

Gatifloxacin‐containing 4‐month ATT regimens compared to standard 6‐month ATT regimens for drug‐sensitive pulmonary tuberculosis

Patient or population: adults with drug‐sensitive pulmonary tuberculosis
Setting: low‐ and middle‐income countries in sub‐Saharan Africa and India
Intervention: gatifloxacin‐containing 4‐month ATT regimen
Comparison: standard 6‐month treatment regimen

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with 6‐month standard ATT

Risk with gatifloxacin‐containing
4‐month ATT

Relapse
Follow‐up: 24 months

70 per 1000

77 more relapses per 1000
(32 more to 128 more)

RR 2.11
(1.56 to 2.84)

1633
(2 RCTs)

⊕⊕⊕⊝
MODERATEa,b

Due to indirectness

The 4‐month regimen probably increases relapse compared to the 6‐month regimen

Death from any cause
Follow‐up: 24 months

29 per 1000

3 fewer deaths per 1000
(14 fewer to 16 more)

RR 0.90
(0.53 to 1.53)

1886
(2 RCTs)

⊕⊕⊕⊝
MODERATEa,b,c

Due to indirectness

The 4‐month regimen probably makes little or no difference in death compared to the 6‐month regimen

Treatment failure

25 per 1000

1 less treatment failure per 1000
(12 fewer to 18 more)

RR 0.93
(0.51 to 1.70)

1657
(2 RCTs)

⊕⊕⊝⊝
MODERATEa,b,c

Due to indirectness

The 4‐month regimen probably makes little or no difference in treatment failure compared to the 6‐month regimen

Acquired drug resistance

12 per 1000

9 fewer with acquired drug resistance per 1000

(12 fewer to 49 more)

RR 0.24

(0.01 to 5.01)

301

(1 RCT)d

⊕⊝⊝⊝
VERY LOWb,e,f

Due to indirectness, risk of bias, and imprecision

We do not know if acquired drug resistance is any different in the 4‐month and the 6‐month regimens

Serious adverse events

24 per 1000

0 fewer serious adverse events per 1000
(10 fewer to 18 more)

RR 1.02
(0.58 to 1.77)

1993
(2 RCTs)

⊕⊕⊕⊝
MODERATEa,b,c

Due to indirectness

The 4‐month regimen probably results in little or no difference in serious adverse events compared to the 6‐month regimen

*The risk in the intervention group (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).
ATT: anti‐tuberculosis treatment; CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence.

High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aNo serious risk of bias: although Jawahar 2013 was assigned high risk of bias for allocation concealment, removal of this trial from the sensitivity analysis did not significantly alter the direction, magnitude, or precision of the effect estimate. Not downgraded.
bDowngraded one level for serious indirectness: trials excluded children and adolescents and people with diabetes mellitus and other comorbid physical conditions and those with alcohol abuse.
cNo serious imprecision: the 95% CI of the risk ratio was wide, but events were few and the sample size was reasonably large; the 95% CI for the absolute estimates did not indicate clinically appreciable benefits for either regimen. Not downgraded.
dOne trial provided data on acquired drug resistance (Jawahar 2013). Merle 2014 reported only drug susceptibility at baseline.
eDowngraded one level for serious risk of bias: allocation concealment was compromised and there were baseline imbalances in proportions with drug resistance at baseline in the sole trial for this outcome (Jawahar 2013).
fDowngraded two levels for very serious imprecision: the data for acquired resistance come from only one trial with 301 participants, and this trial did not evaluate resistance to gatifloxacin.

Figuras y tablas -
Summary of findings 2. Gatifloxacin‐containing 4‐month ATT regimens compared to standard 6‐month ATT regimens for drug‐sensitive pulmonary tuberculosis
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Table 1. Summary of outcomes in included studies

Study ID

(Acronym)

Gillespie 2014

(REMoxTB)

Jawahar 2013

Jindani 2014

(RIFAQUIN)

Merle 2014

(OFLOTUB)

Velayutham 2014

Setting

Multiple sites in Africa (Kenya, South Africa, Tanzania, Zambia), Asia (China, India, Malaysia Thailand), Latin America (Mexico)

6 sites in 2 cities in India

6 cities in 4 countries in Africa (Botswana, South Africa, Zambia, Zimbabwe)

5 countries in Africa (Benin, Guinea, Kenya, Senegal, South Africa)

2 cities in India

Participants

Number randomized

1931

429

827

1836

801

Age

Adults (> 18 years)

Adults (> 18 years)

Adults (> 18 years)

Adults (18 to 65 years)

Adults (> 18 years)

HIV infection

Included (if CD4 count > 250 cells/μL and not on ART); 110 (7%)

Excluded

Included (if CD4 count > 150/mm³ and not on ART; 158 (27%)

Included if not stage 3 or 4 disease and not on ART; 304 (17%)

Excluded

Diagnosis of TB

Positive sputum smears on 2 occasions

Culture‐confirmed susceptibility to rifampicin, isoniazid, pyrazinamide, and moxifloxacin

Newly diagnosed pulmonary TB with at least 2 positive sputum cultures. Confirmed by culture and MDR‐TB excluded, susceptibility to ofloxacin (as proxy for moxifloxacin)

2 sputum samples that were positive for tubercle bacilli on direct smear microscopy

No resistance to isoniazid, rifampicin, or moxifloxacin

Acid‐fast bacilli in 2 consecutive sputum smears; confirmed by culture (solid medium) and drug sensitivity tests to rifampicin, isoniazid, ethambutol, streptomycin, and gatifloxacin

2 positive sputum smear smears for tuberculosis. Culture‐confirmed and MDR‐TB ruled out; susceptible to ofloxacin (as proxy for moxifloxacin)

Intervention(s) and comparator

Duration of ATT

4 monthsa

6 months

4 monthsb

6 months

4 months

6 monthsc

4 months

6 months

4 monthsa

6 months

Regimens

2HRZM/2HRM

+

2MRZE/2MR

2HRZE/4HR

2(HRZG)₃/

2 (HRG)₃

2(HRZM)₃/2(HRM)₃

2(HRZE)₃ /4(HR)₃

2MRZE/

2P₂M₂

2HRZE/

4HR

2HRZG/

2HRG

2HRZE/4HR

3HRZM

+

2HRZM/

2RHM

+

2HRZM/

2(RHM)₃

+

2HRZM/

2(RHEM)₃

2(HRZE)₃/

4(HR)₃

Number allocated

655 + 636 = 1291

640

141

118

170

275

275

917

919

629

172

Late screening failures excluded after allocation

38 + 32

= 70

40

5

3

5

36

35

62

51

13

8

Number eligible

1231

600

136

115

165

239

240

852

868

616

164

Number analysed in m‐ITT analysis (% of those allocated)

568 + 551 = 1119

(87)

555

(87)

136

(97)

115

(98)

165

(97)

193

(70)

188

(68)

791

(86)

794

(86)

590

(94)

151

(88)

Number analysed in per‐protocol analysis (% of those allocated)

514 + 524

=

1038

(80)

510

(80)

131

(93)

113

(96)

159

(94)

165

(60)

163

(59)

651

(71)

601

(65)

As above

Number analysed in ancillary analysis (ITT) (% of those allocated)

617 + 604

= 1221 (94)

600

(94)

Not done

239

(87)

240 (87)

Not reported

Not reported

Outcomes reported

Relapse

Relapse within 18 months after randomization in those with negative culture with treatment. Relapse strains were those shown to be identical on 24‐locus MIRU analysis

LJ solid media and MGIT liquid media used for culture

Recurrence of TB over 24 months after treatment in those with a favourable response with treatment: either bacteriologic recurrence (LJ solid media) or clinical/radiologic recurrence
Relapse not differentiated from re‐infection but majority occurred within 6 months after treatment

Relapse within 12 to 18 months after treatment. Two positive cultures within a period of 4 months without an intervening negative culture). Re‐infections differentiated from relapse through genotyping (MIRU‐VNTRs)

LJ solid media used for culture in some centres, MGIT liquid media in others, and both in some centres

Recurrence of TB over 24 months after treatment proven bacteriologically (2 consecutive positive sputum samples a day apart) or clinically

Genotyping (MIRU‐VNTRs) results available for only 70/140 (55%) of those with culture confirmed recurrence. Most were relapses

Not reported

Deaths

All deaths

TB deaths

Reported (only non‐TB deaths occurred)

All deaths

TB deaths

Death during treatment

Death after treatment

Not reported

Treatment discontinuation

Includes those who did not complete treatment, relocated, or withdrew consent

Includes those who did not complete treatment and those lost to follow‐up

Includes change in treatment due to adverse events, loss to follow‐up, and other treatment changes

Includes those who withdrew consent during treatment and dropouts

Reported but disaggregated data for each group not available

Positive smear/ sputum culture at 2 months

Reported using LJ solid media (used in this review) and MGIT liquid media for all randomized participants excluding late screening failures

Reported using LJ solid media for all randomized participants excluding late screening failures

Reported but disaggregated data for moxifloxacin 4‐month and 6‐month treatment groups not available

Data also not available for all participants from LJ media

Reported for 752 in the 4‐month and 759 in the 6‐month regimens (88% and 87% of those eligible, respectively)

Culture using LJ solid media

Reported for 590

(94%) in the 4‐month and 151

(88%) in the 6‐month regimens

Acquired drug resistance

Reported

Reported

Reported

Not reported

Not reported

Treatment failure

Includes culture confirmed and not confirmed

Includes culture confirmed and unconfirmed

Culture confirmed

Includes culture confirmed failure

Not reported

Serious adverse events

Reported for all randomized participants excluding late screening failures. Grade 3 and 4 severity (DAIDS 2009)

Deduced from adverse events reported for all randomized participants excluding late screening failures. Not graded

Reported for all participants randomized who took 1 dose and assessed as severe or life‐threatening during and 2 weeks after treatment. grade 3 and 4 severity (DAIDS 2009)

Reported for 1692 (92%) of all randomized participants.

grade 3 and 4 severity (DAIDS 2009)

Deduced from adverse events reported. Not graded

Other adverse events

Not reported

Reported

Not reported

QT prolongation

Hyperglycaemic episodes

Reported

Abbreviations: ART: anti‐retroviral treatment; ATT: anti‐tuberculosis treatment; E: ethambutol; G: gatifloxacin; H: isoniazid; ITT: intention‐to‐treat; LJ: Löwenstein‐Jensen; M: moxifloxacin; MGIT: mycobacterial growth indicator tube; MIRU‐VNTRs: mycobacterial interspersed repetitive unit–variable number tandem repeats; m‐ITT: modified intention‐to‐treat; P: rifapentine; R: rifampicin; Z: pyrazinamide.

Leading numbers in regimens indicate duration in months. Drugs were administered daily, except when given thrice weekly as indicated by subscripts.

aData from moxifloxacin‐containing shortened regimens combined for data synthesis.
bData from the 2 shortened regimens compared separately with standard 6‐month regimens.
cData from an additional arm evaluating moxifloxacin‐containing 6‐month regimen not included.

Figuras y tablas -
Table 1. Summary of outcomes in included studies
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Table 2. Sensitivity analysis: moxifloxacin‐based 4‐month versus standard 6‐month ATT regimens

Primary outcome: relapse

Trial ID

Gillespie 2014

Jawahar 2013

Jindani 2014

Regimens

4 months

6 months

4 months

6 months

4 months

6 months

aModified‐ITT analysis (primary analysis)

110/1119

(9.8%)

13/555

(2.3%)

11/108

(10.1%)

10/155

(6.5%)

27/165

(16.4%)

6/163

(3.7%)

aPer‐protocol analysis

110/1038

(10.6%)

12/510

(2.4%)

11/107

(10.1%)

10/152

(6.6%)

26/165

(15.8%)

5/163

(3.1%)

bSensitivity analysis imputing missing data

126/1184

(10.7%)

14/577

(2.4%)

11/114

(9.7%)

10/159

(6.3%)

36/225

(16.0%)

71/232

(2.6%%)

Abbreviations: ATT: anti‐tuberculosis treatment; ITT: intention‐to‐treat.

aAs reported in trial reports.
bIncludes in the denominators for each trial arm all randomized participants minus those excluded post randomization due to ineligibility (not confirmed TB, or drug resistant), those who died, and those who experienced treatment failure. The difference in this denominator and the denominator in per‐protocol analyses are missing data. Relapse rates for missing people were imputed from rates in the per‐protocol analysis for each trial arm.

Figuras y tablas -
Table 2. Sensitivity analysis: moxifloxacin‐based 4‐month versus standard 6‐month ATT regimens
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Table 3. Sensitivity analysis: gatifloxacin‐based 4‐month versus standard 6‐month ATT regimens

Primary outcome: relapse

Trial ID

Jawahar 2013

Merle 2014

Regimen

4 months

6 months

4 months

6 months

aModified‐ITT analysis (primary analysis)

19/122

(15.6%)

10/155

(6.5%)

101/694

(14.6%)

47/662

(7.1%)

aPer‐protocol analysis

19/121

(15.7%)

10/152

(6.6%)

98/651

(15.1%)

44/601

(7,3%)

bSensitivity analysis imputing missing data

19/132

(14.4%)

10/159

(6.3%)

122/786

(15.5%)

61/774

(7,9%)

Abbreviations: ATT: anti‐tuberculosis treatment; ITT: intention‐to‐treat.

aAs reported in trial reports.
bIncludes in the denominators for each trial arm all randomized participants minus those excluded post randomization due to ineligibility (not confirmed TB, or drug resistant), those who died, and those who experienced treatment failure. The difference in this denominator and the denominator in per‐protocol analyses are missing data. Relapse rates for missing people were imputed from rates in the per‐protocol analysis for each trial arm.

Figuras y tablas -
Table 3. Sensitivity analysis: gatifloxacin‐based 4‐month versus standard 6‐month ATT regimens
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Comparison 1. Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Relapse Show forest plot

3

2265

Risk Ratio (M‐H, Fixed, 95% CI)

3.56 [2.37, 5.37]

2 Relapse: subgroup analysis Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Moxifloxacin replacing ethambutol

2

1386

Risk Ratio (M‐H, Fixed, 95% CI)

2.74 [1.69, 4.43]

2.2 Moxifloxacin replacing isoniazid

2

1424

Risk Ratio (M‐H, Fixed, 95% CI)

4.89 [3.02, 7.92]

3 Relapse: sensitivity analysis accounting for missing data Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 Modified‐ITT analysis

3

2265

Risk Ratio (M‐H, Fixed, 95% CI)

3.56 [2.37, 5.37]

3.2 Per‐protocol analysis

3

2135

Risk Ratio (M‐H, Fixed, 95% CI)

3.79 [2.48, 5.78]

3.3 Imputing missing data

3

2524

Risk Ratio (M‐H, Fixed, 95% CI)

3.83 [2.58, 5.70]

4 Death from any cause Show forest plot

3

2760

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.65, 1.75]

5 Treatment discontinuation Show forest plot

3

2335

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.78, 1.61]

6 Positive sputum culture/smear at 8 weeks Show forest plot

3

2828

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.22, 1.13]

6.1 Moxifloxacin replacing isoniazid or ethambutol in 4‐month ATT regimen

2

2087

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.45, 1.20]

6.2 Moxifloxacin augmenting standard 6‐month ATT regimen

1

741

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.15, 0.39]

7 Treatment failure Show forest plot

3

2282

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.33, 1.52]

8 Acquired drug resistance Show forest plot

3

2282

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.08, 1.31]

9 Serious adverse events Show forest plot

4

3548

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.74, 1.27]

9.1 Moxifloxacin replacing standard drugs in 4‐month ATT regimens

3

2760

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.72, 1.26]

9.2 Moxifloxacin augmenting standard 6‐month ATT regimens

1

788

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.45, 3.06]
Figuras y tablas -
Comparison 1. Moxifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens
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Comparison 2. Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Relapse Show forest plot

2

1633

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [1.56, 2.84]

2 Relapse: sensitivity analysis accounting for missing data Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Modified‐ITT analysis

2

1633

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [1.56, 2.84]

2.2 Per‐protocol analysis

2

1525

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [1.55, 2.87]

2.3 Modified‐ITT analysis (all eligible participants ‐ imputing missing data)

2

1851

Risk Ratio (M‐H, Fixed, 95% CI)

2.01 [1.53, 2.63]

3 Death from any cause Show forest plot

2

1886

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.53, 1.53]

4 Treatment discontinuation Show forest plot

2

1657

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.46, 1.08]

5 Positive sputum culture at 8 weeks Show forest plot

2

1818

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.80, 1.23]

6 Treatment failure Show forest plot

2

1657

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.51, 1.70]

7 Acquired drug resistance Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.01, 5.01]

8 Serious adverse events Show forest plot

2

1993

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.58, 1.77]
Figuras y tablas -
Comparison 2. Gatifloxacin‐containing 4‐month ATT versus standard 6‐month ATT regimens
Ir a la tabla de la revisión