Aseffa, A;
Chukwu, JN;
Vahedi, M;
Aguwa, EN;
Bedru, A;
Mebrahtu, T;
Ezechi, OC;
... 4FDC Study Group, .; + view all
(2016)
Efficacy and Safety of 'Fixed Dose' versus 'Loose' Drug Regimens for Treatment of Pulmonary Tuberculosis in Two High TB-Burden African Countries: A Randomized Controlled Trial.
PLoS One
, 11
(6)
, Article e0157434. 10.1371/journal.pone.0157434.
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Abstract
BACKGROUND: There are limited data on the performance of the use of fixed-dose combination (FDC) TB drugs when used under programmatic settings in high TB-endemic countries. We evaluated the efficacy and safety of FDC versus loose formulation (LF) TB treatment regimens for treatment of pulmonary TB (PTB) in the context of actual medical practice in prevailing conditions within programmatic settings in five sites in two high TB-burden African countries. METHODS: A two-arm, single-blind, randomized clinical trial comparing FDCs with separate LFs involving 1000 adults newly diagnosed with culture positive PTB was conducted at five sites in two African countries between 2007 and 2011. Participants were randomized to receive daily treatment with anti-TB drugs given as either FDC or separate LFs for 24 weeks (intensive phase- 8 weeks of isoniazid, rifampicin, ethambutol and pyrazinamide; continuation phase- 16 weeks of rifampicin and isoniazid). Primary outcome measures were microbiological cure and safety at the end of six months' treatment; pre-specified non-inferiority margin for difference in cure rate was 4%. The primary efficacy analysis was based on the modified intent to treat (mITT) cohort comprising all randomized patients with a positive baseline culture result for TB and who received at least one dose of study treatment. Patients missing end of treatment culture results were considered failures. Further analyses were done in which mITT patients without an end of treatment (EOT) culture were excluded in a complete case analysis (mITTcc) and a per protocol cohort analysis defined as mITTcc patients who received at least 95% of their intended doses and had an EOT culture result. RESULTS: In the mITT analysis, the cure rate in the FDC group was 86.7% (398/459) and in the LF group 85.2% (396/465) (difference 1.5-% (90% confidence interval (CI) (-2.2%- 5.3%)). Per Protocol analysis showed similar results: FDC 98.9% (359/363) versus LF 96.9% (345/356), (difference 2.0% (90% CI: 0.1%- 3.8%)). The two arms showed no significant differences in terms of safety, early culture conversion and patient adherence to treatment. INTERPRETATION: The comparison of the two drug regimens satisfied the pre-specified non-inferiority criterion. Our results support the WHO recommendations for the use of FDC in the context of actual medical practice within health services in high TB-endemic countries. TRIAL REGISTRATION: ISRCTN Registry 95204603.
| Type: | Article |
|---|---|
| Title: | Efficacy and Safety of 'Fixed Dose' versus 'Loose' Drug Regimens for Treatment of Pulmonary Tuberculosis in Two High TB-Burden African Countries: A Randomized Controlled Trial |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0157434 |
| Publisher version: | http://doi.org/10.1371/journal.pone.0157434 |
| Language: | English |
| Additional information: | © 2016 Aseffa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Adult, Africa, Aged, Antitubercular Agents, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Therapy, Combination, Ethambutol, Female, Humans, Isoniazid, Male, Middle Aged, Pyrazinamide, Rifampin, Sputum, Treatment Outcome, Tuberculosis, Pulmonary |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1503998 |
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