| Protocol No: | ECCT/16/12/02 | Date of Protocol: | 14-05-2015 |
| Study Title: | Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: A randomized, open-label, controlled phase 3 clinical trial. |
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RE: Amendmen t Submission of protocol titled: "Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: A randomi zed, open-label, controlled phase 3 clinical trial Version 2.0 dated 14 May 2015. A5349/KEMRI/SERU/CCR/0027/3253 The above mentioned protocol was initially approved by PPB ECCT through a l etter dated I 0 January 201 7. Si nce then, the protocol went through review a t WRAIR and changes have been made to address queries that were raised by the WRAIR JRB. The purpose of this memo i s to submit amendment due to WRAIR input for ECCT review and approval. KEMRI SERU reviewed and approved the amendment on 31 Aug 2017 via the attached letter dated 04 Sep 2017. 1. The Site Specific Addend um has been revised from versi on 2.4 dated 26 May 2016 to 2.10 dated 19 Jan 2017. 2. English & Kiswahili Informed Consent Form, has been revised from version 2.4 dated 26 May 2016 to version 2.9 dated 19 Jan 2017. 3. Engl ish & Kiswahili Assent has been revised from version 2.3 dated 26 May 2016 to version 2.6 dated 08 Dec 2016. Detai ls of the amendment are on the attached amendment sum mary. This submission includes the following: ATTACHMENTS: 1. Summary of changes for the SSA from version 2.4 to 2.10, ICFs from version 2.4 to 2.9 and Assents from version 2.3 to 2.6. 2. Core/Sponsor Protocol version 2.0 dated 14 May 2015. 3. SSA version 2.10 dated 19 Jan 2017-clean and track changes. 4. ICF English version 2.9 dated 19 Jan 2017- clean and track changes 5. ICF Kiswahili version 2.9 dated 19 Jan 2017 - clean and track changes 6. Assent English version 2.6 dated 08 Dec 2016- clean and track changes 7. Assent Kiswahili version 2.6 dated 08 Dec 2016- clean and track changes 8. KEMRI SERU amendment approval dated 04 Sep 2017. If you require additional infommtion OR clarification please do not hesitate to contact the PI at 0722 749 789 OR e-mail Isaac.tsikhutsu@usamru-k.org. Thank you for your time and review. | |
| Study Objectives: | 1.OBJECTIVES1.1PRIMARY OBJECTIVE9.1.1 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. 9.1.2 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.
1.2SECONDARY OBJECTIVES9.2.1 To evaluate the safety of the investigational regimens. 9.2.2 To evaluate the tolerability of the investigational regimens. 9.2.3 To collect and assess biospecimens from consenting participants for the purpose of research on discovery and validation of TB biomarkers. 9.2.4 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. 9.2.5 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. 9.2.6 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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| Laymans Summary: | 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 217/100 000, whilst in Kericho County, the rate is 246 /100 000. TB treatment takes 6 months in Kenya and this relatively long treatment is associated with relatively poor compliance and high relapse rates than if the regimen were shorter. This contributes to increase in patient morbidity and mortality, Mycobacterium tuberculosis transmission and drug resistant TB. Treatment adherence is critical in TB treatment success and a shorter regimen may improve adherence. This highlights the need to shorten further the duration of TB treatment. This study aims to evaluate the efficacy, safety and tolerability of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya. Male or female participants who are 12 years or older with smear positive pulmonary TB will be enrolled and randomized into either 8 weeks of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol followed by 18 weeks of Rifampicin and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Ethambutol followed by 9 weeks of Rifapentine and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Moxifloxacin followed by 9 weeks of Rifapentine, Isoniazid and Moxifloxacin. The Kericho site will recruit 80-100 participants and follow them up for 18 months. If shorter TB treatment regimen is efficacious compared to current 6 month TB treatment duration, this will potentially have important public health implications by increasing TB cure rates, potentially reducing TB transmission and preventing emergency of MDR TB. |
| Abstract of Study: | 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 217/100 000, whilst in Kericho County, the rate is 246 /100 000. TB treatment takes 6 months in Kenya and this relatively long treatment is associated with relatively poor compliance and high relapse rates than if the regimen were shorter. This contributes to increase in patient morbidity and mortality, Mycobacterium tuberculosis transmission and drug resistant TB. Treatment adherence is critical in TB treatment success and a shorter regimen may improve adherence. This highlights the need to shorten further the duration of TB treatment. This study aims to evaluate the efficacy, safety and tolerability of 2 treatment regimens versus the standard drug susceptible TB treatment regimen currently used in Kenya. Male or female participants who are 12 years or older with smear positive pulmonary TB will be enrolled and randomized into either 8 weeks of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol followed by 18 weeks of Rifampicin and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Ethambutol followed by 9 weeks of Rifapentine and Isoniazid or 8 weeks of Rifapentine, Isoniazid, Pyrazinamide, Moxifloxacin followed by 9 weeks of Rifapentine, Isoniazid and Moxifloxacin. The Kericho site will recruit 80-100 participants and follow them up for 18 months. If shorter TB treatment regimen is efficacious compared to current 6 month TB treatment duration, this will potentially have important public health implications by increasing TB cure rates, potentially reducing TB transmission and preventing emergency of MDR TB. |