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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 May 2023
• Main ID: NCT02581527
• Date of registration: 19/10/2015
• Prospective Registration: Yes
• Primary sponsor: St George's, University of London
• Public title: A Randomised Trial to Evaluate Toxicity and Efficacy of 1200mg and 1800mg Rifampicin for Pulmonary Tuberculosis RIFASHORT
• Scientific title: An International Multicentre Controlled Clinical Trial to Evaluate 1200mg and 1800mg Rifampicin Daily for Four Months in the Reduction of the Duration of Standard Treatment of Pulmonary Tuberculosis
• Date of first enrolment: February 1, 2017
• Target sample size: 672
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02581527
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Botswana, Guinea, Mexico, Nepal, Pakistan, Peru, Uganda, United Kingdom

Contacts

• Name: Amina Jindani, MD
• Affiliation: Professor

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Tuberculosis

Intervention(s)

Drug: Rifampicin

Drug: Ethambutol

Drug: Pyrazinamide

Drug: Isoniazid

Primary Outcome(s)

The occurrence of grade 3 or 4 adverse events at any time during chemotherapy. [Time Frame: 18 months]

the primary outcome measure is the combined rate of failure at the end of treatment and relapse during the subsequent 12 months in smear positive patients in the modified intent to treat population. [Time Frame: 18 months]

Secondary Outcome(s)

Time to unfavourable outcome in the modified intent-to-treat and per protocol sputum smear microscopy-positive population. [Time Frame: 18 Months]

Combined unfavourable endpoint (rate of failure at the end of treatment and relapse) measured 18 months from randomisation in the Xpert MTB/RIF positive (i) modified intent-to-treat and (ii) per protocol populations [Time Frame: 18 months]

Any adverse event, up to one month after completion of treatment, graded according to the DAIDS criteria [Time Frame: 1 month after end of treatment (7 months (Control), 5 months (Study regimens) )]

Per protocol analysis of the primary efficacy outcome (the combined rate of failure at the end of treatment and relapse during the subsequent 12 months in smear positive patients) [Time Frame: 18 months]

Sputum cultures positive for M.tuberculosis at 8 and 12 weeks from randomisation. [Time Frame: 18 months]

Secondary ID(s)

15.0190

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

London School of Hygiene and Tropical Medicine

University of Botswana