Optimization of the TB Treatment Regimen Cascade

NCT ID: NCT02153528

Last Updated: 2020-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 701 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2017-08-01

Brief Summary

• Hypothesis: Double dose rifampicin together with earlier monitoring of sputum conversion using vital staining reduces unfavorable outcome of Cat. 1 first-line TB treatment without excess serious toxicity, and allows early switch to specific treatment of MDR-TB without using Cat. 2 retreatment regimen

• General study design: This open label, randomised clinical trial is intended as a pilot study on the efficacy and safety of high-dose rifampicin and feasibility and added value of auramine and/or FDA vital staining sputum smear after 2 weeks of intensive treatment phase. If this proof-of-concept study provides substantial indication of benefit without indication of excess toxicity, the data from the study will be used to design a larger scale, cluster-randomized study. The aim of this cluster randomised study would be to provide definite proof of the benefit of the intervention on adverse treatment outcomes and lack of excess toxicity associated with high dose rifampicin. In addition, the cluster-randomized study would provide a more precise assessment of the suppression and prevention of (acquired) resistance endpoints.

An interim analysis is thus planned at the time the last recruited patient finishes treatment, i.e. about 9 months after the end of recruitment. It will focus on assessment of drug toxicity versus suggested benefits of the intervention. This analysis will be primarily performed for the go/no-go decision and design considerations for the cluster-randomized trial. The decision on proceeding to the cluster randomized study will be based on the absence of excess toxicity, a trend toward a reduction of unfavourable outcomes (excluding relapse), and possible favourable effects on initially present low-resistance mutations / mutations acquired during treatment. It will also allow to adapt the design of the larger study particularly regarding the algorithm for resistance screening, and whether or not treatment shortening could be justified with rapid initial conversion.

Conditions

Tuberculosis, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard TB treatment

Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease

Group Type: ACTIVE_COMPARATOR

Standard TB treatment

Intervention Type: DRUG

Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease

double rimfampicin

2HREZ/4HR Cat. 1, modified by using double dose rifampicin throughout

Group Type: EXPERIMENTAL

double rimfampicin

Intervention Type: DRUG

Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained

Interventions

double rimfampicin

Compared to standard regimen dosing of rifampicin is doubled, while standard dose isoniazid, pyrazinamide and ethambutol are maintained

Intervention Type: DRUG

Standard TB treatment

Standard regimen for TB treatment according to guidelines of the International Union against Tuberculosis and Lung Disease

Intervention Type: DRUG

Other Intervention Names

Intervention arm; Control arm

Eligibility Criteria

Inclusion Criteria

• Diagnosed with smear-positive pulmonary TB
• 15 years or older
• Able and willing to provide written informed consent

Exclusion Criteria

• contacts of MDR-TB patients and other MDR-TB suspects diagnosed with resistance on rapid DST for rifampicin performed prior to start of treatment according to NTP guidelines
• smear-negative pulmonary and extra-pulmonary TB cases
• patients in need of hospitalization because of very bad general condition or complications
• patients with clinically active liver disease, for the study defined as jaundice confirmed by a local Medical Officer (Government)
• any known HIV-positive patient (although none are expected)
• any patient with known hepatitis B or C infection
• pregnant women; in addition, patients in the intervention arm who become pregnant during treatment will be switched to the control arm

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National TB control Programme Bangladesh

OTHER

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: collaborator

Damien Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aung Kya Jai Maug, MD

Role: PRINCIPAL_INVESTIGATOR

Damien Foundation Bangladesh

Locations

Damien Foundation Bangladesh TB project in Greater Mymensingh district (8 selected clinics)

Dhaka, Greater Mymensingh District, Bangladesh

Countries

Bangladesh

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

OneRIF

Identifier Type: -

Identifier Source: org_study_id