NCT02581527

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

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 672 (actual)
• Sponsor: St George's, University of London · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Type of design An open-label 3-arm trial to compare a standard 6-month control regimen with two 4-month treatment regimens for the treatment of tuberculosis (TB). Disease/patients studied The trial will include 654 patients newly diagnosed with pulmonary TB with sputum positive or negative for TB on microscopy but with a positive result on a GeneXpert Test with organisms fully sensitive to rifampicin The treatment regimens - Control and Experimental Patients enrolled in the trial will be randomly allocated to receive one of the following three chemotherapy treatment regimens: 1. Control regimen (R10): The standard regimen of isoniazid, pyrazinamide and ethambutol plus 10 mg/kg rifampicin for the initial 8 weeks, followed by isoniazid and rifampicin (at the same dose size) for an additional 4 months (2HRZE/4HR)A. 2. Study regimen 1(SR1): 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70 and more kg) of rifampicin will be given throughout the four months (2EHR 1200Z/2HR1200)B. 3. Study regimen 2(SR2): 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70 and more kg) of rifampicin will be given throughout the four months (2EHR1800Z/2HR1800)C. 1.1 Outcome measures Primary outcome measure 1. Since the objective of the trial is to reduce treatment duration by increasing the dose of rifampicin, 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. 2. The occurrence of grade 3 or 4 adverse events at any time during chemotherapy.

Conditions

• Pulmonary Tuberculosis

Interventions

Type	Name	Description
DRUG	Rifampicin	Rifampicin 150mg (Control arm); Rifampicin 1200mg (Regimen 1); Rifampicin 1800mg (Regimen 2)
DRUG	Isoniazid	Isoniazid 75mg - all arms
DRUG	Ethambutol	Ethambutol 275mg - all arms
DRUG	Pyrazinamide	Pyrazinamide 400mg - all arms

Timeline

• Start date: 2017-02-01
• Primary completion: 2022-01-01
• Completion: 2022-07-31
• First posted: 2015-10-21
• Last updated: 2023-04-27

Locations

6 sites across 6 countries: Botswana, Guinea, Nepal, Pakistan, Peru, Uganda