Dataset Information

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.

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.

SUBMITTER: Aseffa A

PROVIDER: S-EPMC4913909 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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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.

Aseffa Abraham A Chukwu Joseph N JN Vahedi Mahnaz M Aguwa Emmanuel N EN Bedru Ahmed A Mebrahtu Tesfamariam T Ezechi Oliver C OC Yimer Getnet G Yamuah Lawrence K LK Medhin Girmay G Connolly Cathy C Rida Wasima W Aderaye Getachew G Zumla Alimuddin I AI Onyebujoh Philip C PC

PloS one 20160620 6

<h4>Background</h4>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.<h4>Methods</h4>A two-arm, single-bli ...[more]

PMID: 27322164

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Project description:BackgroundSuboptimal patient adherence to pharmacological therapy of type 2 diabetes may be due in part to pill burden. One way to reduce pill burden in patients who need multiple medications is to use fixed-dose combinations. Our study aimed to compare the effects of fixed-dose combination versus loose-dose combination therapy on medication adherence and persistence, health care utilization, therapeutic safety, morbidities, and treatment modification in patients with type 2 diabetes over three years.MethodsUsing administrative data, we conducted a retrospective controlled cohort study comparing type 2 diabetes patients who switched from monotherapy to either a fixed-dose combination or a loose-dose combination. Adherence was assessed as the primary endpoint and calculated as the proportion of days covered with medication. After using entropy balancing to eliminate differences in observable baseline characteristics between the two groups, we applied difference-in-difference estimators for each outcome to account for time-invariant unobservable heterogeneity.ResultsOf the 990 type 2 diabetes patients included in our analysis, 756 were taking a fixed-dose combination and 234 were taking a loose-dose combination. We observed a statistically significantly higher change in adherence (year one: 0.22, p<0.001, year two: 0.25, p<0.001, and year three: 0.29, p<0.001) as well as higher persistence and a smaller change in the number of drug prescriptions in each of the three years in the fixed-dose combination group compared to the loose-dose combination group. The differences were most pronounced in patients who were poorly adherent, had a high pill burden, or did not have a severe concomitant disease.ConclusionOur results indicate that taking a fixed-dose combination can lead to a significant improvement in adherence to pharmacological therapy of type 2 diabetes compared to a loose-dose combination. In particular, these findings suggest that reducing pill burden may improve disease management among patients with more complex medication demand and patients who have demonstrated poor medication adherence.

Project description:BackgroundTuberculosis remains a major public health priority and is the second leading cause of mortality from infectious disease worldwide. TB case detection rates are unacceptably low for men, the elderly and children. Disruptions in TB services due to the COVID-19 pandemic may have exacerbated these and other inequalities.MethodsWe modelled trends in age- and sex- disaggregated case notifications for all forms of new and relapse TB reported to the World Health Organization for 45 high TB, TB/HIV and MDR-TB burden countries from 2013 to 2019. We compared trend predicted notifications to observed notifications in 2020 to estimate the number of people with TB likely to have missed or delayed diagnosis. We estimated the risk ratio (RR) of missed or delayed TB diagnosis for children (aged < 15 years) or the elderly (aged ≥ 65 years) compared to adults (aged 15-64 years) and women compared to men (both aged ≥ 15 years) using a random-effects meta-analysis.ResultsAn estimated 195,449 children (95% confidence interval, CI: 189,673-201,562, 37.8% of an expected 517,168), 1,126,133 adults (CI: 1,107,146-1,145,704, 21.8% of an expected 5,170,592) and 235,402 elderly (CI: 228,108-243,202, 28.5% of an expected 826,563) had a missed or delayed TB diagnosis in 2020. This included 511,546 women (CI: 499,623-523,869, 22.7%, of an expected 2,250,097) and 863,916 men (CI: 847,591-880,515, 23.0% of an expected 3,763,363). There was no evidence globally that the risk of having TB diagnosis missed or delayed was different for children and adults (RR: 1.09, CI: 0.41-2.91), the elderly and adults (RR: 1.40, CI: 0.62-3.16) or men and women (RR: 0.59, CI: 0.25-1.42). However, there was evidence of disparities in risk by age and/or sex in some WHO regions and in most countries.ConclusionsThere is no evidence at an aggregate global level of any difference by age or sex in the risk of disruption to TB diagnosis as a result of the COVID-19 pandemic. However, in many countries, disruptions in TB services have been greater for some groups than others. It is important to recognise these context-specific inequalities when prioritising key populations for catch-up campaigns.

Dataset Information

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.

Publications

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.

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