Modified BPaL Regimen for Managing Pre-XDR TB and MDR (TI/NR) TB in India

• Status: Recruiting
• Trial end date: 2024-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Existing problem with DR TB management:

Injectable regimens for longer duration with toxicity Poor adherence, treatment failures, continued transmission

Need of the study:

Oral regimens of shorter duration Improved treatment adherence Implementation of community-based models of care Reduction in direct costs and indirect costs of patients Improved treatment outcomes

Need for shorter, tolerable and effective regimen

Hence modified BPaL regimen is designed to study the newer shorter oral in varying doses of Linezolid for pre XDR Tb patients and MDR TI/NR patients

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tuberculosis Research Centre, India
• Collaborators: BJ Medical College, Ahmedabad; Govt. Medical College, Surat; International Union Against Tuberculosis and Lung Diseases; KGMU, Lucknow; NITRD, New Delhi; RBIPMT, Delhi; Sarvodaya Charitable Trust Hospital, Ghatkopar, Mumbai; Shatabdi Centenary Hospital, Govandi, Mumbai; SN Medical College, Agra
• Treatments: Bedaquiline; Linezolid

Criteria

Inclusion Criteria:

1. Adults aged between 18 years - 65 years

2. Pulmonary Pre-XDR-TB, patients [with documented evidence of resistance to rifampicin with or without isoniazid resistance AND additional resistance to any fluoroquinolones by conventional DST (culture-based1) or rapid DST (Xpert MTB/RIF or Trunat MTB/RIF or LPA) from a certified laboratory] OR MDR-TBTI/NR patients [with documented treatment intolerance or non-response to MDR TB treatment regimen for 6-months or more when the participant was adherent to the treatment regimen]

3. Bodyweight of ≥30 kg (in light clothing and no shoes)

4. Provide written, informed consent before all study-related procedures

5. Provide consent to HIV testing2 (if an HIV test was performed within 1 month before the study start, it should not be repeated as long as documentation can be provided [ELISA and/or Western Blot]).

6. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) < 2.5 x ULN; Total bilirubin lesser than ULN when accompanied by an increase in other liver function tests.

7. QTcF less than or equal to 450 at baseline

8. Female patients should not be pregnant or should be using a birth control method. They should be willing to continue practicing birth control methods (barrier or non-barrier contraceptive methods including oral contraceptives) throughout the treatment period, or history of post-menopausal for the past 12 months.

Exclusion Criteria:

Non-DST based criteria

1. Intolerance or risk of toxicity from medicine in the treatment regimens (e.g. drug-drug interactions)

2. Patient who has received more than 2 weeks of Bedaquiline or Linezolid before the first dose of BPaL regimen

3. Pregnancy or Lactating women

4. All forms of Extrapulmonary TB (Lymph node TB associated with Pulmonary DR-TB and pleural effusion associated with pulmonary TB can be considered for inclusion )

5. HIV infected patient having a CD4+ cell count of ≤ 50 cells/µL;

6. Currently having an uncontrolled cardiac arrhythmia that requires medication

7. Have any of the following QTcF interval characteristics at screening:

1. QTcF ≥ 450 at baseline & normal electrolytes, ECG to be repeated after 6 hours and if both ECGs show QTc>450 then the patient should not be challenged with cardiotoxic drugs.

2. History of additional risk factors for Torsade de Pointes, e.g. heart failure, hypokalaemia, family history of long QT syndrome;

8. Any condition in the Investigator's opinion (i.e., an unstable disease such as uncontrolled diabetes on insulin3 or cardiomyopathy), where participation would compromise the well-being of the patient or prevent, limit or confound protocol-specified assessments.

9. Very seriously ill patients (Karnofsky scores < 50 within last 30 days)

10. If results of the serum chemistry panel or, hematology are outside the normal reference range (as given below), the patient may still be considered if the physician judges that the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable.

• Hypokalaemia, hypomagnesemia, and hypocalcemia should be corrected before a patient receiving any cardiotoxic drugs. (hypothyroidism is not exclusion criteria, to be considered with simultaneous thyroxine replacement therapy and close monitoring)

• Haemoglobin level of < 9.0 g/dl or Platelet count <1,00,000 /mm3

• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >2.5 x ULN; Total bilirubin greater ULN when accompanied by an increase in other liver function tests

11. Grade III or IV peripheral neuropathy

DST based criteria

a. if the result for DST (FQ, LZD)4 is not available and h/o more than 2 weeks consumption of drugs used in the study regimen