Novel Triple-dose Tuberculosis Retreatment Regimen

NCT ID: NCT04260477

Last Updated: 2025-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-01

Study Completion Date

2025-09-30

Brief Summary

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To determine if a high-dose first-line regimen is non-inferior (non-inferiority margin 10%) in terms of safety to the same regimen at regular dosing, in previously treated patients with rifampicin-susceptible recurrent Tuberculosis (TB).

Detailed Description

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Stage 1: This is a pragmatic open-label multi-stage randomized clinical trial. Potential participants will be screened and enrolled in Damien Foundation (DF) clinics participating in the trial.

First we will perform a two-arm study with 6EHRZ as control arm and 6EH³R³Z as intervention arm. If at interim analysis the intervention arm is not considered to be non-inferior to the control arm, the intervention stops and enrolment will continue in a an adapted intervention arm and the control arm (6EHRZ). Otherwise, enrolment continues to 6EHRZ and 6EH³R³Z.

Observational study (stage 2): The DSMB members agreed due to safety concerns to continuing the study as a cohort with only the control arm. The control regimen will remain the same (6EHRZ).

As per routine practice, during treatment patients are in daily contact with the direct observed therapy (DOT) supervisor and minimally monthly clinic visits are scheduled for monitoring of safety and treatment response.

Additionally, liver function tests will be performed at fixed intervals during treatment. Six month and one year after treatment completion or cure the patient will be checked for relapse with systematic sputum acid-fast bacilli (AFB)-microscopy and TB culture.

Conditions

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Multidrug-resistant Tuberculosis Pulmonary Tuberculosis Tuberculosis Resistance to Tuberculostatic Drugs

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Providers in the TB clinics and lab technicians in the Niger clinics and labs will not be blinded to the prescribed regimen. However, lab technicians working in the Institute of Tropical Medicine (ITM) lab will be blinded to the prescribed regimen. Also the statistician will be blinded to the prescribed regimen until the first interim analysis is completed.

Study Groups

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6EH³R3Z

(Rifampicin (R)/ Isoniazid (H) / Pyrazinamide (Z)/Ethambutol (E)) 6-month high-dose treatment; New high-dose isoniazid / high-dose rifampicin retreatment regimen (6EH³R3Z) - that includes triple-dose rifampicin (R3; 30 mg/kg), and triple-dose isoniazid (H3; 15 mg/kg), complemented with pyrazinamide (Z) and ethambutol (E).

Group Type EXPERIMENTAL

6EH³R³Z

Intervention Type DRUG

A triple dose is defined as the triple of the routine dose used for a specific WHO weight band. Hence, the mg/kg within a weigh-band varies, as is the case in routine practice.

Dosing takings into consideration the fixed dose combination (FDC) tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E). Dosage relies on tables with dosage by weight-bands used by WHO for the Cat. 1 regimen. The dosage used for the intensive phase of the Cat. 1 regimen applies for the whole treatment duration. A double dose of H and R is added to the recommended normal dose for adults (WHO,2003)

6EHRZ

Standard of care: 6-month 6RHZE regimen with dose combination tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E)

Group Type ACTIVE_COMPARATOR

6EHRZ

Intervention Type DRUG

Recommended normal dose adults (WHO, 2003)

* H: 5 (4-6) mg/kg/day
* R: 10 (8-12) mg/kg/day
* Z: 25 (20-30)mg/kg/day
* E: 15 (15-18)mg/kg/day

Interventions

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6EH³R³Z

A triple dose is defined as the triple of the routine dose used for a specific WHO weight band. Hence, the mg/kg within a weigh-band varies, as is the case in routine practice.

Dosing takings into consideration the fixed dose combination (FDC) tablets (one tablet: 150 mg R + 75 mg H + 400 mg Z + 275mg E). Dosage relies on tables with dosage by weight-bands used by WHO for the Cat. 1 regimen. The dosage used for the intensive phase of the Cat. 1 regimen applies for the whole treatment duration. A double dose of H and R is added to the recommended normal dose for adults (WHO,2003)

Intervention Type DRUG

6EHRZ

Recommended normal dose adults (WHO, 2003)

* H: 5 (4-6) mg/kg/day
* R: 10 (8-12) mg/kg/day
* Z: 25 (20-30)mg/kg/day
* E: 15 (15-18)mg/kg/day

Intervention Type DRUG

Other Intervention Names

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Ethambutol; isoniazid; rifampicin; pyrazinamide triple dose isoniazid triple dose rifampicin Ethambutol; isoniazid; rifampicin; pyrazinamide

Eligibility Criteria

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Inclusion Criteria

* All newly registered patients with smear-positive recurrent pulmonary TB
* Adults as well as children (no age limit)
* Able and willing to provide written informed consent
* Added for stage 2: lives within 5 km of a health facility with a medical doctor

Exclusion Criteria

* All patients with TB initially resistant to rifampicin on Xpert MTB/RIF testing
* Patients transferred to a health facility not supported by the Damien Foundation
* Patients previously enrolled in the trial, and with another episode of rifampicin-susceptible TB during the study period
* Those with grade III elevation of liver function tests at baseline, or with clinically active liver disease at screening
* Pregnant or breastfeeding woman
* HIV co-infected patients requiring treatment with a protease inhibitor
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Damien Foundation

OTHER

Sponsor Role collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sani Kadri

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health, Niger

Locations

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Damien Foundation

Niamey, , Niger

Site Status RECRUITING

Countries

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Niger

Central Contacts

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Natacha Herssens, MSc

Role: CONTACT

003232470778

Tom Decroo, MD

Role: CONTACT

003232470535

Facility Contacts

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Bassirou Souleymane

Role: primary

+227 94985157

Other Identifiers

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ITM202001

Identifier Type: -

Identifier Source: org_study_id

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