A Randomised Trial to Evaluate Toxicity and Efficacy of 1200mg and 1800mg Rifampicin for Pulmonary Tuberculosis

• Status: Active, not recruiting
• Trial end date: 2022-04-30
• Target enrollment: 0
• Participant gender: All

Summary

In this trial, the investigators are assessing whether giving an increased dose of rifampicin to patients receiving the standard treatment for tuberculosis is safe and, when given for 4 months only, will also result in greater and faster killing of the tubercle bacillus in the lungs and result in relapse rates similar to those found in the World Health Organisation (WHO) recommended standard 6 month regimen.

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

Details

• Lead Sponsor: St George's, University of London
• Collaborators: London School of Hygiene and Tropical Medicine; University of Botswana
• Treatments: Ethambutol; Isoniazid; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

1. GeneXpert sputum positive, rifampicin susceptible, newly diagnosed pulmonary tuberculosis will be included even if they are microscopy negative.

2. No previous anti-tuberculosis chemotherapy.

3. Patients ≥ 18 years

4. Consent to participation in the trial and to HIV testing

5. Provide informed consent.

6. Patient has a stable home address within easy reach of the treatment facility and likely to remain there for the next 18 months.

7. Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an Intrauterine Contraceptive Device (IUCD) in place for the duration of the treatment phase

Exclusion Criteria:

1. Patients with rifampicin resistance identified by GeneXpert or by direct susceptibility testing (late exclusions).

2. Has any condition that may prove fatal during the study period.

3. Has TB meningitis.

4. Has pre-existing non-tuberculous disease likely to prejudice the response to, or assessment of, treatment e.g. insulin-dependent diabetes, liver or kidney disease, blood disorders, peripheral neuritis, and severe thrombocytopenia, rash, increase of bilirubin and other diseases that are likely to be contraindicated with rifampicin

5. Is female and known to be pregnant, or breast feeding.

6. Is suffering from a condition likely to lead to uncooperative behaviour such as psychiatric illness or alcoholism.

7. Has contraindications to any medications in the study regimens

8. Is HIV positive

9. Haemoglobin <7g/l

10. Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 5 times the upper limit of normal (ULN) for that laboratory

11. Creatinine clearance (CrCl) of < 30mls/min. Calculated as CrCl (mL/min) = N x [140-age (years)] x weight (kg) Serum creatinine (micromol/L) Where N = 1.23 males, 1.04 females

12. Has glucose in urine

13. Weight < 35kg