endTB trials for Multidrug-Resistant TB

Phase 3

Completed

Conditions: Health Condition 1: A150- Tuberculosis of lung

Registration Number: CTRI/2020/07/026414

Lead Sponsor: Medicins Sans Frontieres

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 31

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 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.

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. 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 regi

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.Timepoint: week 73

Secondary Outcome Measures

Name	Time	Method
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. <br/ ><br>Safety: Proportion of patients: <br/ ><br>who died for any cause; <br/ ><br>with grade 3 or greater AEs and serious adverse events of any grade by 73 and 104 weeks; <br/ ><br>with Adverse Events of Special Interest by 73 and 104 weeks.Timepoint: Week 39, week 73 and week 104