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CTRI Number  CTRI/2020/07/026414 [Registered on: 07/07/2020] Trial Registered Prospectively
Last Modified On: 28/07/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   endTB trials for Multidrug-Resistant TB 
Scientific Title of Study   endTB: Evaluating Newly approved Drugs for multidrug-resistant TB 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NCT02754765 Version 3.3 dated 14 Feb 2019  ClinicalTrials.gov 
NCT02754765 Version 3.3.2 dated 22 October 2019  DCGI 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Samiran Panda 
Designation  Director ICMR NARI and Coordinating Principal Investigator endTB Trials 
Affiliation  ICMR-National AIDS Research Institute 
Address  ICMR-NARI G Block, MIDC Road, Bhosari Pune -411026

Pune
MAHARASHTRA
411026
India 
Phone    
Fax    
Email  director@nariindia.org  
 
Details of Contact Person
Scientific Query  
Name  Dr Samiran Panda 
Designation  Director ICMR NARI and Coordinating Principal Investigator endTB Trials 
Affiliation  ICMR-National AIDS Research Institute 
Address  ICMR-NARI G Block, MIDC Road, Bhosari Pune -411026

Pune
MAHARASHTRA
411026
India 
Phone    
Fax    
Email  director@nariindia.org  
 
Details of Contact Person
Public Query  
Name  Dr Samiran Panda 
Designation  Director ICMR NARI and Coordinating Principal Investigator endTB Trials 
Affiliation  ICMR-National AIDS Research Institute 
Address  ICMR-NARI G Block, MIDC Road, Bhosari Pune -411026

Pune
MAHARASHTRA
411026
India 
Phone    
Fax    
Email  director@nariindia.org  
 
Source of Monetary or Material Support  
UNITAID Global Health Campus, Chemin du Pommier 40, 5th floor, 1218 Grand-Saconnex Geneva, Switzerland  
 
Primary Sponsor  
Name  Medicins Sans Frontieres 
Address  Avenue Jean Jaures, 14-34, 75019, Paris, France  
Type of Sponsor  Other [Non Government Organisation] 
 
Details of Secondary Sponsor  
Name  Address 
Doctors Without Borders India Pvt Ltd  C 384 Ground Floor Defence Colony, New Delhi 110024 
 
Countries of Recruitment     Georgia
India
Kazakhstan
Lesotho
Pakistan
Peru
South Africa  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sandip Patil  Aundh Chest Hospital Pune  Aundh Camp, New Sangavi, Pune
Pune
MAHARASHTRA 		 7804092428

spatil@nariindia.org 
Dr Chetankumar Jain  Sarvodaya Hospital  Ghatkopar, Mumbai
Mumbai
MAHARASHTRA 		 9892741309

drchetankumarjain@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
Ethics Committee National AIDS Research Institute Pune  Approved 
The Foundation For Medical Research IREC  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: A150||Tuberculosis of lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Standard of Care  Control-arm treatment will be constructed and delivered according to local standard of care and consistent with WHO guidelines for the conventional regimen, and may include bedaquiline and/or delamanid in addition to other drugs. 
Intervention  Experimental regimens will contain bedaquiline and/or delamanid and up to 4 companion drugs.   Multidrug treatment regimens for fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Experimental regimens will contain bedaquiline and/or delamanid and up to 4 companion drugs and will be delivered for 39 weeks.  
 
Inclusion Criteria  
Age From  15.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  A patient will be eligible for randomization if s/he:
1. Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to rifampin (RIF) and susceptible to fluoroquinolones, diagnosed by validated rapid molecular test;
2. Is 15 years and more of age;
3. Is willing to use effective contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilized must agree to use two methods of contraception (e.g., a hormonal method and a barrier method) unless their partner has had a vasectomy; men who have not had a vasectomy must agree to use condoms;
4. Provides informed consent for study participation; additionally a legal representative of patients considered minor per local laws should also provide consent;
5. Lives in a dwelling that can be located by study staff and expects to remain in the area for the duration of the study. 
 
ExclusionCriteria 
Details  A patient will not be eligible for randomization if s/he:
1. Has known allergies or hypersensitivity to any of the investigational drugs;
2. Is known to be pregnant or is unwilling or unable to stop breast-feeding an infant;
3. Is unable to comply with treatment or follow-up schedule;
4. Has any condition (social or medical) which, in the opinion of the site principal investigator, would make study participant unsafe;
5. a. Has had exposure (intake of the drug for 30 days or more) in the past five years to bedaquiline, delamanid, linezolid, or clofazimine, or has proven or likely resistance to bedaquiline, delamanid, linezolid, or clofazimine (e.g., household contact of a DR-TB index case who died or experienced treatment failure after treatment containing bedaquiline, delamanid, linezolid, or clofazimine or had resistance to one of the listed drugs); exposure to other anti-TB drugs is not a reason for exclusion.b. Has received second-line drugs for 15 days or more prior to screening visit date in the current MDR/RR-TB treatment episode. Exceptions include: (1) patients whose treatment has failed according to the WHO definition151 and who are being considered for a new treatment regimen; (2) patients starting a new treatment regimen after having been “lost to follow-up” according to the WHO definition149 and, (3) patients in whom treatment failure is suspected (but not confirmed according to WHO definition), who are being considered for a new treatment regimen, and for whom the Clinical Advisory Committee (CAC) consultation establishes eligibility.
6. Has one or more of the following:
Hemoglobin treater than equal to 7.9 g/dL;
Uncorrectable electrolytes disorders:
Total Calcium < 7.0 mg/dL (1.75 mmol/L);
Potassium < 3.0 mEq/L (3.0 mmol/L) or more than or equal to 6.0 mEq/L (6.0 mmol/L);
Magnesium < 0.9 mEq/L (0.45 mmol/L);
Serum creatinine > 3 x ULN;
Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) more than/equal to 3 x ULN;
Total bilirubin 3 x ULN;
Albumin < 2.8 g/dL;
Unless otherwise specified, Grade 4 result as defined by the MSF Severity Scale (Appendix 2) on any of the screening laboratory tests.
7. Has cardiac risk factors defined as:
An arithmetic average of the two ECGs with highest QTcF intervals of greater than or equal to 450 ms. Retesting to reassess eligibility will be allowed using an unscheduled visit during the screening phase;
Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome);
Electrocardiographic evidence of either:
Complete left bundle branch block or right bundle branch block; OR
Incomplete left bundle branch block or right bundle branch block and QRS complex duration > 120 msec on at least one ECG;
Having a pacemaker implant;
Congestive heart failure;
Evidence of second- or third-degree heart block;
Bradycardia as defined by sinus rate less than 50 bpm;
Personal or family history of Long QT Syndrome;
Personal history of arrhythmic cardiac disease, with the exception of sinus arrhythmia;
Personal history of syncope (i.e. cardiac syncope not including syncope due to vasovagal or epileptic causes).
8. Is currently taking part in another trial of a medicinal product;
9. Is taking any medication that is contraindicated with the medicines in the trial regimen which cannot be stopped (with or without replacement) or requires a wash-out period longer than 2 weeks
 
 
Method of Generating Random Sequence   Adaptive randomization, such as minimization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
The primary efficacy outcome is the proportion of participants with favorable outcome at week 73. A favorable outcome will be defined based on the presence of negative culture results at weeks 65 and 73 and based on the bacteriological, radiological and clinical evolution.  week 73 
 
Secondary Outcome  
Outcome  TimePoints 
Efficacy: Proportion of participants with favorable outcome at week 39 and 104. A favorable outcome will be defined based on the presence of negative culture results at weeks 36 and 39 and weeks 97 and 104 and based on the bacteriological, radiological and clinical evolution.
Safety: Proportion of patients:
who died for any cause;
with grade 3 or greater AEs and serious adverse events of any grade by 73 and 104 weeks;
with Adverse Events of Special Interest by 73 and 104 weeks. 		 Week 39, week 73 and week 104 
 
Target Sample Size   Total Sample Size="750"
Sample Size from India="55" 
Final Enrollment numbers achieved (Total)= "754"
Final Enrollment numbers achieved (India)="31" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   15/07/2020 
Date of Study Completion (India) 08/04/2023 
Date of First Enrollment (Global)  18/02/2017 
Date of Study Completion (Global) 08/04/2023 
Estimated Duration of Trial   Years="3"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Completed 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  
endTB trial is randomized, controlled, open-label, Phase III clinical trials conducted in a highly heterogeneous patient population (including participants from sites in four continents, with different prevalence of HIV and other co-morbidities) and will result in high-quality evidence that will be generalizable and transformative for the global policies of MDR-TB management.The experimental regimens mainly rely on newly approved or repurposed drugs and avoid drugs to which high rates of resistance have been reported in MDR-TB patient populations.
endTB is a randomized clinical trial that evaluates five all-oral 9 months regimens for FQ-susceptible MDR-TB (endTB regimens 1-5) in comparison to the current 18-20 month standard of care (control). The sample size needed is of 750 participants. Randomization is adapted based on early treatment outcomes using a Bayesian approach.Trial will be conducted at two sites in India  and planned to be initiated in June/July 2020.
 
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