| Protocol No: | ECCT/15/08/01 | Date of Protocol: | 24-11-2014 |
| Study Title: | Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: a randomized, open-label, controlled, phase 3 clinical trial |
| Study Objectives: |
PRIMARY OBJECTIVES:
To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single
substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the
duration of treatment for drug-susceptible pulmonary tuberculosis
To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes
moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to
determine whether it is possible to reduce to seventeen weeks the duration of treatment for
drug-susceptible pulmonary tuberculosis
Secondary Objectives
To evaluate the safety of the investigational regimens
To evaluate the tolerability of the investigational regimens
To collect and assess biospecimens from consenting participants for the purpose of
research on discovery and validation of TB biomarkers
To determine the correlation of mycobacterial and clinical markers with time to culture
conversion, culture status at completion of eight weeks of treatment, treatment failure,
and relapse.
To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The
main objectives of the PK/PD study are to characterize study drug PK parameters and
to determine relationships between treatment outcomes and PK parameters.
To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among
patients with TB/HIV co-infection taking efavirenz-based combination antiretroviral
therapy and TB treatment with rifapentine
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| 2 | PRIMARY OBJECTIVES: To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase, to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis 5.1 Secondary Objectives To evaluate the safety of the investigational regimens To evaluate the tolerability of the investigational regimens To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers To determine the correlation of mycobacterial and clinical markers with time to culture conversion, culture status at completion of eight weeks of treatment, treatment failure, and relapse. To conduct a pharmacokinetic/pharmacodynamic (PK/PD) study of the test drugs. The main objectives of the PK/PD study are to characterize study drug PK parameters and to determine relationships between treatment outcomes and PK parameters. To evaluate the pharmacokinetics of efavirenz-based antiretroviral treatment among patients with TB/HIV co-infection taking efavirenz-based combination antiretroviral therapy and TB treatment with rifapentine |
| Laymans Summary: |
This stud is a Rifapentine-Containing Treatment shortening regimens for pulmonary tuberculosis, A randomized, open-label, controlled phase 3 clinical trial in
Kisumu County. It is an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 noninferiority trial. This study will be conducted in various TBTC and ACTG sites across the world In Kenya it will be conducted at the KEMRI/CDC clinical research center at the Jaramogi Oginga Odinga Teaching and referral hospital.
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| 2 | A5349 is a randomized, open-label, controlled phase 3 clinical trial in Kisumu County. The study aims to find out the safety, tolerability and efficacy of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya |
| Abstract of Study: | Background: Tuberculosis (TB) is one of the most important global health problems. According to recent estimates from the World Health Organization (WHO), 8.6 million new cases and 1.3 million deaths from TB occurred in 2012. The vast majority of TB cases and TB deaths are in developing countries. The spread of HIV has fuelled the TB epidemic, and TB is the leading cause of death among patients infected with HIV. The national case notification rate is 283/100000, whilst in KisumuCounty, the rate is 317 /100 000.TB treatment takes 6 months in Kenya and this relatively long treatment is associated with high relapse rates, relatively poor compliance than if the regimen were shorter. It is essential to shorten the treatment further, with efficacy proven in the new regimen. Treatment adherence is critical in TB treatment success and a shorter regimen may improve adherence. This study aims to find out the safety, tolerability and efficacy of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya. This, multicentre, randomized, controlled, open-label, (3-arm, phase 3 non-inferiority) clinical trial will enrol smear positive participants in Kisumu County. They will be randomized into either of the following 3 treatment arms; 2 RHZE/4HR for 26 weeks, 2PHZE/4PH for 17 weeks, 2PHZM/4PHM for 17 weeks. A shorter, more tolerable, efficacious treatment regimen will lead to better compliance, reduce pill burden and drug toxicity whilst improving TB treatment outcomes. |