Novel Triple-dose Tuberculosis Retreatment Regimens: How to Overcome Resistance Without Creating More

NCT03862248 | Withdrawn Phase 3 DMC

• 1 other identifier: TriDoRe
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Drug-resistance is a major challenge for tuberculosis (TB) care programs. The new WHO guideline recommends adding levofloxacin in previously treated patients with isoniazid-resistant rifampicin-susceptible TB. The investigators believe that such a retreatment regimen may result in acquired resistance to fluoroquinolone, the core drug of multidrug-resistant TB (MDR-TB) regimen, and thus threaten the effectiveness of the fluoroquinolone-based MDR-TB treatment regimen. Therefore the investigators propose to study if regimens strengthened by using high-dose first-line drugs, either a triple dose of isoniazid or a triple dose of rifampicin, are non-inferior to the WHO recommended levofloxacin-strengthened regimen. If one of both high-dose regimens would be non-inferior, it could replace the levofloxacin-strengthened regimen.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Bacteriological effectiveness (proportion of relapse-free cure excluding deaths and lost-to-follow-up)

  To study if the bacteriological effectiveness of two high-dose regimens is non-inferior to the WHO recommended levofloxacin-strengthened regimen in patients with rifampicin-susceptible recurrent TB. Relapse-free cure is based on sputum smear and culture-result.

  18 months (6-month treatment + 12-month follow-up period)

Secondary Outcomes (9)

• Frequency of resistance to the different drug components at screening.

  At screening (day 0)

• Identify predictors of bacteriological effectiveness

  18 months (6-month treatment + 12-month follow-up period)

• Programmatic effectiveness (i.e proportion of participants with relapse-free cure)

  18 months (6-month treatment + 12-month follow-up period)

• Number of SAEs and study-specific adverse events of the different retreatment regimens

  up to month 6

• Negative predictive value of two-week FDA

  2 weeks after start of treatment

Study Arms (3)

High-Dose Isoniazid

EXPERIMENTAL

New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg

Drug: 6EH³RZ

High-Dose Rifampicin

EXPERIMENTAL

New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg

Drug: 6EHR³Z

World Health Organisation (WHO) regimen

ACTIVE COMPARATOR

WHO levofloxacin-strengthened regimen (6EHRZLfx)

Drug: 6EHRZLfx

Interventions

6EH³RZ DRUG

New high-dose isoniazid retreatment regimen (6EH³RZ) - H 15mg/kg

High-Dose Isoniazid

6EHR³Z DRUG

New high-dose rifampicin retreatment regimen (6EHR³Z) - R 30mg/kg

High-Dose Rifampicin

6EHRZLfx DRUG

WHO levofloxacin-strengthened regimen (6EHRZLfx)

World Health Organisation (WHO) regimen

Eligibility Criteria

• Gender Eligibility Details: participant eligibility is based on self-representation of gender identity
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients transferred to a health facility not supported by Damien Foundation will be excluded. This includes patients diagnosed with HIV/TB-coinfection.

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Damien Foundation: collaborator

Study Sites (1)

Damien Foundation

Dhaka, Bangladesh

Location

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Tom Decroo, MD

  Insitute of Tropical Medicine Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: March 5, 2019
• Study Start: September 30, 2019
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: January 21, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)