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Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB)

Primary Purpose

Tuberculosis, Multidrug-Resistant, Infection, Bacterial, Pulmonary Tuberculoses

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bedaquiline
Delamanid
Clofazimine
Levofloxacin
Moxifloxacin
Linezolid
Pyrazinamide
Control arm MDR-TB regimen, consistent with WHO guidelines
Sponsored by
Médecins Sans Frontières, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberculosis, Multidrug-Resistant focused on measuring bedaquiline, delamanid, linezolid, clofazimine, tuberculosis, MDR-TB XDR-TB

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 of age;
  3. Is willing to use contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilized must agree to use contraception 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.

Exclusion Criteria:

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. 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 ≤ 7.9 g/dL;
    • Uncorrectable electrolytes disorders:
    • Calcium < 7.0 mg/dL;
    • Potassium < 3.0 or ≥6.0 mEq/L;
    • Magnesium < 0.9 mEq/L;
    • Serum creatinine > 3 x ULN;
    • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 3 x ULN;
    • Total bilirubin ≥ 1.5 x ULN if accompanied by AST or ALT > ULN or total bilirubin ≥ 2 x ULN when other liver function results are in the normal range;
    • Grade 4 result on any of the specified laboratory tests as defined by the MSF Severity Scale.
  7. Has cardiac risk factors defined as:

    • A confirmed QTc interval of greater than or equal to 450 ms. Retesting to reassess eligibility will be allowed once 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 greater or equal to 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. Concurrent participation in another trial of any medication used or being studied for TB treatment, as defined in cited documents.
  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.

Sites / Locations

  • National Center for Tuberculosis and Lung Diseases
  • Aundh Chest Hospital
  • Center of Phthisiopulmonology of Almaty Health Department
  • National Center for Tuberculosis Problems
  • City Centre of Phthisiopulmonology
  • Partners In Health Lesostho
  • The Indus Hospital
  • Institute of Chest Disease,
  • Centro de Investigación del Hospital Nacional Hipólito Unanue
  • Centro de Investigación de Enfermedades Neumológicas del Hospital Nacional Sergio Bernales
  • Hospital Nacional Dos de Mayo Parque Historia de la Medicina
  • Medecins Sans Frontieres Belgium

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Active Comparator

Arm Label

endTB regimen 1 (BeLiMoZ)

endTB regimen 2 (BeLiCLeZ)

endTB regimen 3 (BeDeLiLeZ)

endTB regimen 4 (DeLiCLeZ)

endTB regimen 5 (DeCMoZ)

endTB regimen 6 (Control)

Arm Description

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.

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.

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.

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.

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.

endTB regimen 6 is the control regimen.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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: 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; 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; 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.
Early Treatment Response (culture conversion)
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; 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; Change in time to positivity (TTP) in MGIT over 8 weeks.
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: In the experimental arm, addition or replacement of one or more drugs; In the control arm, addition or replacement of two or more drugs; Death from any cause; At least one culture result (from a sample collected between weeks 36 and 39) is positive; The patient is not assessable because the last available culture result is from a sample collected before week 36.
Week 73 Survival
At 73 weeks, the proportion of patients who died of any cause
Week 104 Survival
At 104 weeks, the proportion of patients who died of any cause
Week 73 Safety
The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 73 weeks
Week 104 Safety
The proportion of participants with grade 3 or greater AEs and serious adverse events (SAEs) of any grade by 104 weeks
Week 73 Safety: proportion of patients with AESIs
The proportion of patients with AESIs by 73 weeks
Week 104 Safety: proportion of patients with AESIs
The proportion of patients with AESIs by 104 weeks

Full Information

First Posted
April 25, 2016
Last Updated
August 21, 2023
Sponsor
Médecins Sans Frontières, France
Collaborators
Partners in Health, Harvard Medical School (HMS and HSDM), Epicentre, Institute of Tropical Medicine, Belgium, Socios En Salud, Peru, Interactive Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT02754765
Brief Title
Evaluating Newly Approved Drugs for Multidrug-resistant TB
Acronym
endTB
Official Title
Evaluating Newly Approved Drugs for Multidrug-resistant TB (endTB): A Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
June 2023 (Actual)
Study Completion Date
June 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Médecins Sans Frontières, France
Collaborators
Partners in Health, Harvard Medical School (HMS and HSDM), Epicentre, Institute of Tropical Medicine, Belgium, Socios En Salud, Peru, Interactive Research and Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Multidrug-Resistant, Infection, Bacterial, Pulmonary Tuberculoses
Keywords
bedaquiline, delamanid, linezolid, clofazimine, tuberculosis, MDR-TB XDR-TB

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
754 (Actual)

8. Arms, Groups, and Interventions

Arm Title
endTB regimen 1 (BeLiMoZ)
Arm Type
Experimental
Arm Description
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.
Arm Title
endTB regimen 2 (BeLiCLeZ)
Arm Type
Experimental
Arm Description
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.
Arm Title
endTB regimen 3 (BeDeLiLeZ)
Arm Type
Experimental
Arm Description
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.
Arm Title
endTB regimen 4 (DeLiCLeZ)
Arm Type
Experimental
Arm Description
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.
Arm Title
endTB regimen 5 (DeCMoZ)
Arm Type
Experimental
Arm Description
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.
Arm Title
endTB regimen 6 (Control)
Arm Type
Active Comparator
Arm Description
endTB regimen 6 is the control regimen.
Intervention Type
Drug
Intervention Name(s)
Bedaquiline
Other Intervention Name(s)
Sirturo
Intervention Type
Drug
Intervention Name(s)
Delamanid
Other Intervention Name(s)
Deltyba, OPC-67683
Intervention Type
Drug
Intervention Name(s)
Clofazimine
Other Intervention Name(s)
Lamprene
Intervention Type
Drug
Intervention Name(s)
Levofloxacin
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Intervention Type
Drug
Intervention Name(s)
Linezolid
Intervention Type
Drug
Intervention Name(s)
Pyrazinamide
Intervention Type
Drug
Intervention Name(s)
Control arm MDR-TB regimen, consistent with WHO guidelines
Intervention Description
Control arm MDR-TB regimen, consistent WHO guidelines
Primary Outcome Measure Information:
Title
Week 73 Efficacy
Description
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
Secondary Outcome Measure Information:
Title
Week 104 Efficacy
Description
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: 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; 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; 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
Title
Early Treatment Response (culture conversion)
Description
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; 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; Change in time to positivity (TTP) in MGIT over 8 weeks.
Time Frame
Week 8 after randomization
Title
Week 39 Efficacy
Description
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: In the experimental arm, addition or replacement of one or more drugs; In the control arm, addition or replacement of two or more drugs; Death from any cause; At least one culture result (from a sample collected between weeks 36 and 39) is positive; 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
Title
Week 73 Survival
Description
At 73 weeks, the proportion of patients who died of any cause
Time Frame
Week 73 after randomization
Title
Week 104 Survival
Description
At 104 weeks, the proportion of patients who died of any cause
Time Frame
Week 104 after randomization
Title
Week 73 Safety
Description
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
Title
Week 104 Safety
Description
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
Title
Week 73 Safety: proportion of patients with AESIs
Description
The proportion of patients with AESIs by 73 weeks
Time Frame
Week 73 after randomization
Title
Week 104 Safety: proportion of patients with AESIs
Description
The proportion of patients with AESIs by 104 weeks
Time Frame
Week 104 after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A patient will be eligible for randomization if s/he: Has documented pulmonary tuberculosis due to strains of M. tuberculosis resistant to rifampin (RIF) and susceptible to fluoroquinolones, diagnosed by validated rapid molecular test; Is ≥ 15 years of age; Is willing to use contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilized must agree to use contraception unless their partner has had a vasectomy; men who have not had a vasectomy must agree to use condoms; Provides informed consent for study participation; additionally a legal representative of patients considered minor per local laws should also provide consent; Lives in a dwelling that can be located by study staff and expects to remain in the area for the duration of the study. Exclusion Criteria: A patient will not be eligible for randomization if s/he: Has known allergies or hypersensitivity to any of the investigational drugs; Is known to be pregnant or is unwilling or unable to stop breast-feeding an infant; Is unable to comply with treatment or follow-up schedule; Any condition (social or medical) which, in the opinion of the site principal investigator, would make study participant unsafe; 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. Has one or more of the following: Hemoglobin ≤ 7.9 g/dL; Uncorrectable electrolytes disorders: Calcium < 7.0 mg/dL; Potassium < 3.0 or ≥6.0 mEq/L; Magnesium < 0.9 mEq/L; Serum creatinine > 3 x ULN; Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ 3 x ULN; Total bilirubin ≥ 1.5 x ULN if accompanied by AST or ALT > ULN or total bilirubin ≥ 2 x ULN when other liver function results are in the normal range; Grade 4 result on any of the specified laboratory tests as defined by the MSF Severity Scale. Has cardiac risk factors defined as: A confirmed QTc interval of greater than or equal to 450 ms. Retesting to reassess eligibility will be allowed once 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 greater or equal to 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). Concurrent participation in another trial of any medication used or being studied for TB treatment, as defined in cited documents. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Guglielmetti, MD
Organizational Affiliation
Médecins Sans Frontières, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carole Mitnick, Sc.D
Organizational Affiliation
Harvard Medical School (HMS and HSDM)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Center for Tuberculosis and Lung Diseases
City
Tbilisi
ZIP/Postal Code
0101
Country
Georgia
Facility Name
Aundh Chest Hospital
City
Pune
Country
India
Facility Name
Center of Phthisiopulmonology of Almaty Health Department
City
Almaty
ZIP/Postal Code
050030
Country
Kazakhstan
Facility Name
National Center for Tuberculosis Problems
City
Almaty
Country
Kazakhstan
Facility Name
City Centre of Phthisiopulmonology
City
Nur-Sultan
ZIP/Postal Code
020000
Country
Kazakhstan
Facility Name
Partners In Health Lesostho
City
Maseru
Country
Lesotho
Facility Name
The Indus Hospital
City
Karachi
Country
Pakistan
Facility Name
Institute of Chest Disease,
City
Kotri
Country
Pakistan
Facility Name
Centro de Investigación del Hospital Nacional Hipólito Unanue
City
Lima
ZIP/Postal Code
1390
Country
Peru
Facility Name
Centro de Investigación de Enfermedades Neumológicas del Hospital Nacional Sergio Bernales
City
Lima
Country
Peru
Facility Name
Hospital Nacional Dos de Mayo Parque Historia de la Medicina
City
Lima
Country
Peru
Facility Name
Medecins Sans Frontieres Belgium
City
Khayelitsha
ZIP/Postal Code
7784
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35028659
Citation
Hewison C, Khan U, Bastard M, Lachenal N, Coutisson S, Osso E, Ahmed S, Khan P, Franke MF, Rich ML, Varaine F, Melikyan N, Seung KJ, Adenov M, Adnan S, Danielyan N, Islam S, Janmohamed A, Karakozian H, Kamene Kimenye M, Kirakosyan O, Kholikulov B, Krisnanda A, Kumsa A, Leblanc G, Lecca L, Nkuebe M, Mamsa S, Padayachee S, Thit P, Mitnick CD, Huerga H. Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort. Clin Infect Dis. 2022 Sep 29;75(6):1006-1013. doi: 10.1093/cid/ciac019. Erratum In: Clin Infect Dis. 2023 Feb 18;76(4):779.
Results Reference
derived
PubMed Identifier
34563240
Citation
Guglielmetti L, Ardizzoni E, Atger M, Baudin E, Berikova E, Bonnet M, Chang E, Cloez S, Coit JM, Cox V, de Jong BC, Delifer C, Do JM, Tozzi DDS, Ducher V, Ferlazzo G, Gouillou M, Khan A, Khan U, Lachenal N, LaHood AN, Lecca L, Mazmanian M, McIlleron H, Moschioni M, O'Brien K, Okunbor O, Oyewusi L, Panda S, Patil SB, Phillips PPJ, Pichon L, Rupasinghe P, Rich ML, Saluhuddin N, Seung KJ, Tamirat M, Trippa L, Cellamare M, Velasquez GE, Wasserman S, Zimetbaum PJ, Varaine F, Mitnick CD. Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial. Trials. 2021 Sep 25;22(1):651. doi: 10.1186/s13063-021-05491-3.
Results Reference
derived
PubMed Identifier
31676905
Citation
Seung KJ, Khan P, Franke MF, Ahmed S, Aiylchiev S, Alam M, Putri FA, Bastard M, Docteur W, Gottlieb G, Hewison C, Islam S, Khachatryan N, Kotrikadze T, Khan U, Kumsa A, Lecca L, Tassew YM, Melikyan N, Naing YY, Oyewusi L, Rich M, Wanjala S, Yedilbayev A, Huerga H, Mitnick CD. Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis. Clin Infect Dis. 2020 Jul 11;71(2):415-418. doi: 10.1093/cid/ciz1084. Erratum In: Clin Infect Dis. 2023 Jan 13;76(2):374.
Results Reference
derived

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Evaluating Newly Approved Drugs for Multidrug-resistant TB

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