A Phase 3 interventional study of Bedaquiline and Delamanid in Tuberculosis, Multidrug-Resistant, Infection, Bacterial and Pulmonary Tuberculoses, sponsored by Médecins Sans Frontières, France. Completed at 12 sites in 7 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2025-02-10.
Sponsored by Médecins Sans Frontières, France · Phase 3, Interventional, and Treatment
endTB Clinical Trial a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of five new, all-oral, shortened regimens for multidrug-resistant tuberculosis (MDR-TB).
This is a Phase III, randomized, controlled, open-label, non-inferiority, multi-country trial evaluating the efficacy and safety of new combination regimens for MDR-TB treatment.
Regimens examined combine newly approved drugs bedaquiline and/or delamanid with existing drugs known to be active against Mycobacterium tuberculosis (linezolid, clofazimine, moxifloxacin or levofloxacin, and pyrazinamide). The study will enroll in parallel across 5 experimental and 1 standard-of-care control arms. Randomization will be outcome adapted using Bayesian interim analysis of efficacy endpoints. Experimental regimens will contain bedaquiline and/or delamanid and up to 4 companion drugs. Control-arm treatment may contain one of the following (bedaquiline or delamanid) and companion drugs, constructed and delivered according to local standard of care and consistent with WHO guidelines. Trial participation in all arms will last at least until Week 73, and up to Week 104. In the experimental arms, treatment will be for 39 weeks (participants in the experimental arms will be allowed up to 47 weeks to complete the 39-week treatment course) and post-treatment follow up for up to 65 additional weeks. In the control arm, treatment will be delivered according to local standard of care (in consistence with WHO guidance); duration may vary and will be approximately 86 weeks for the conventional regimen and 39-52 weeks for the standardized shorter regimen.
Non-inferiority will be established for any experimental arm if the lower bound of the one-sided 97.5% confidence interval around the difference in favorable outcome between the control and experimental arms is greater than or equal to -12%.
132 studies on the registry are indexed under Tuberculosis, Multidrug-Resistant; 25 are open to participants now.
This study's enrollment of 754 is above the median of 194 across 88 interventional studies indexed under Tuberculosis, Multidrug-Resistant.
Browse Tuberculosis, Multidrug-Resistant studies →Médecins Sans Frontières, France is the lead sponsor of 2 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
A patient will be eligible for randomization if s/he:
Exclusion Criteria:
A patient will not be eligible for randomization if s/he:
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 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.
Has one or more of the following:
Has cardiac risk factors defined as:
Electrocardiographic evidence of either:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Drug: Bedaquiline · Drug: Moxifloxacin · Drug: Linezolid · Drug: Pyrazinamide
Subjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Drug: Bedaquiline · Drug: Clofazimine · Drug: Levofloxacin · Drug: Linezolid · Drug: Pyrazinamide
Subjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Drug: Bedaquiline · Drug: Delamanid · Drug: Levofloxacin · Drug: Linezolid · Drug: Pyrazinamide
Subjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based. Subjects will undergo a linezoilid dose reduction randomization to either 300mg daily or 600mg three times a week after 16 weeks of treatment or after a linezolid-related AE requiring dose reduction, whichever is earlier.
Drug: Delamanid · Drug: Clofazimine · Drug: Levofloxacin · Drug: Linezolid · Drug: Pyrazinamide
Subjects who are randomized to this arm will receive treatment for 39 weeks and post-treatment followup for 65 weeks. Participants may take as long as 47 weeks to complete all doses of a 39-week treatment regimen. Dosing of experimental regimens will be oral and weight based.
Drug: Delamanid · Drug: Clofazimine · Drug: Moxifloxacin · Drug: Pyrazinamide
endTB regimen 6 is the control regimen.
Drug: Control arm MDR-TB regimen, consistent with WHO guidelines
Also known as: Sirturo
Also known as: Deltyba, OPC-67683
Also known as: Lamprene
Control arm MDR-TB regimen, consistent WHO guidelines
Week 73 Efficacy
Proportion of participants with favorable outcome at week 73. A participant's outcome will be classified as favorable at week 73 if the outcome is not classified as unfavorable, and one of the following is true: * The last two culture results are negative. These two cultures must be taken from sputum samples collected on separate visits, the latest between weeks 65 and 73; * The last culture result (from a sputum sample collected between weeks 65 and 73) is negative; and either there is no other post-baseline culture result or the penultimate culture result is positive due to laboratory cross contamination; and bacteriological, radiological and clinical evolution is favorable; * There is no culture result from a sputum sample collected between weeks 65 and 73 or the result of that culture is positive due to laboratory cross contamination; and the most recent culture result is negative; and bacteriological, radiological and clinical evolution is favorable.
Time frame: Week 73 after randomization
Week 104 Efficacy
Proportion of participants with favorable outcome at week 104. • A participant's outcome will be classified as favorable at week 104 if the outcome is not classified as unfavorable, and one of the following is true: 1. The last two cultures are negative. These two cultures must be from sputum samples collected on separate visits, the latest between weeks 97 and 104; 2. The last culture result (from a sputum sample collected between weeks 97 and 104) is negative; and either there is no other post-baseline culture result or the penultimate culture result is positive due to laboratory cross contamination; and bacteriological, radiological and clinical evolution is favorable; 3. There is no culture result from a sputum sample collected between weeks 97 and 104 or the result of that culture is positive due to laboratory cross contamination; and the most recent culture result is negative; and bacteriological, radiological and clinical evolution is favorable.
Time frame: Week 104 after randomization
Early Treatment Response (culture conversion)
1. Proportion of patients with culture conversion assessed in MGIT system (and LJ where possible): 2 consecutive negative cultures from specimens collected at 2 different visits; if there is a missing or contaminated culture between 2 negatives, the definition of conversion is still met; 2. Time to culture conversion: assessed in MGIT system (and LJ where possible): time from treatment initiation to first of 2 consecutive negative cultures; if there is a missing or contaminated culture between 2 negatives, the definition of conversion is still met; 3. Change in time to positivity (TTP) in MGIT over 8 weeks.
Time frame: Week 8 after randomization
Week 39 Efficacy
Proportion of participants with favorable outcome at week 39: • A participant's outcome will be classified as favorable at week 39 if the last culture result (from a sample collected between weeks 36 and 39) is negative; and the outcome is not classified as unfavorable. A participant's outcome will be classified as unfavorable at week 39 in case of: 1. In the experimental arm, addition or replacement of one or more drugs; 2. In the control arm, addition or replacement of two or more drugs; 3. Death from any cause; 4. At least one culture result (from a sample collected between weeks 36 and 39) is positive; 5. The patient is not assessable because the last available culture result is from a sample collected before week 36.
Time frame: Week 39 after randomization
Week 73 Survival
At 73 weeks, the proportion of patients who died of any cause
Time frame: Week 73 after randomization
Week 104 Survival
At 104 weeks, the proportion of patients who died of any cause
Time frame: Week 104 after randomization
Week 73 Safety
The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 73 weeks
Time frame: Week 73 after randomization
Week 104 Safety
The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 104 weeks
Time frame: Week 104 after randomization
Week 73 Safety: proportion of patients with AESIs
The proportion of patients with AESIs by 73 weeks
Time frame: Week 73 after randomization
Week 104 Safety: proportion of patients with AESIs
The proportion of patients with AESIs by 104 weeks
Time frame: Week 104 after randomization
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — After deidentification process most part of variables recorded in the eCRF (no patients name or ID, no site or country location, no dates but intervals from randomization, no birth dates but age at randomization, no information on staff...)
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: From Q4 2024 and will last 5 years renewable.
Access criteria: proposal has scientific value / the scientific question addresses a knowledge gap and avoids duplication without added value and unnecessary competition, and benefits the wider public health community the data requested must be capable of answering the research question, and each variable requested must be required for the successful completion of the research the methodology proposed to answer the research question must be sound conform to the Data Access Guidelines, Ethics Framework, and Conflict of Interest Policy (see on website https://endtb.org/data-sharing-initiative)
Data sharing details ↗ · endtb.org
Ran from Dec 2016 to primary completion in Jun 2023, 78 months.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Bedaquiline · OPC-67683 · Clofazimine · Levofloxacin · Moxifloxacin · Linezolid · Pyrazinamide
Tuberculosis, Multidrug-Resistant →
Médecins Sans Frontières, France