Ultra-Short Course Bedaquiline, Clofazimine, Pyrazinamide and Delamanid Versus Standard Therapy for Drug-Susceptible TB — PRESCIENT  

HIV Clinical Trial

Official title: A Phase IIc, Open-Label, Randomized Controlled Trial of Ultra-Short Course Bedaquiline, Clofazimine, Pyrazinamide and Delamanid Versus Standard Therapy for Drug-Susceptible Tuberculosis (PRESCIENT)

Status Recruiting

Clinical Trial Summary

The PRESCIENT trial is a Phase IIc, open-label, randomized trial that will compare a 12-week regimen of bedaquiline (BDQ), clofazimine (CFZ), pyrazinamide (PZA), and delamanid (DLM) with standard treatment for drug-susceptible pulmonary tuberculosis. Eligible participants will be randomized in a 1:1 ratio to BDQ, CFZ, PZA, and DLM (BCZD) or standard anti-TB therapy.

Participants in the experimental arm with evidence of poor clinical response at the end of therapy will be re-treated with standard TB therapy. The primary analysis is a superiority efficacy comparison of time to liquid culture conversion through 8 weeks in the experimental (BCZD) arm vs. the standard therapy arm. The other key secondary outcome is safety.

Clinical Trial Description

The PRESCIENT trial is a Phase IIc, open-label, randomized trial that will compare a 12-week regimen of bedaquiline (BDQ), clofazimine (CFZ), pyrazinamide (PZA), and delamanid (DLM) with standard treatment for drug-susceptible pulmonary tuberculosis. Eligible participants will be randomized in a 1:1 ratio to BDQ, CFZ, PZA, and DLM (BCZD) or standard anti-TB therapy. Randomization will be stratified by presence of lung cavitation and HIV status.

Participants will be randomized to one of two arms:

Arm 1 (Experimental): BDQ 200 mg for 12 weeks + PZA 1000 - 2000 mg (according to weight) for 12 weeks + CFZ 300 mg for 2 weeks, followed by 100 mg for 10 weeks + DLM 200 mg for 12 weeks, all given once daily.

Arm 2 (Standard of Care): RIF, INH, EMB and PZA for 8 weeks, followed by RIF and INH for 18 weeks.

Medications will be given daily in fixed dose combinations at standard weight-based doses. Adherence will be supported through automated reminders and monitored remotely in real time with Wisepill electronic adherence monitoring devices or with directly observed treatment. Participants in the experimental arm with evidence of poor clinical response will be re-treated with standard TB therapy. The primary analysis is a superiority efficacy comparison of time to liquid culture conversion through 8 weeks in the experimental (BCZD) arm vs. the standard therapy arm. Participants will have extended post-treatment follow up to evaluate clinical efficacy as a secondary composite outcome measure at 86 weeks after randomization (74 weeks after completion of experimental therapy, when most relapses are expected to occur). The other key secondary outcome is safety, measured as the proportion with new Grade 3 or higher adverse events; we shall focus on QTcF prolongation and hepatitis as adverse events of special interest. Through an efficient Phase IIc design, the PRESCIENT trial will test microbiological efficacy, evaluate safety, and detect treatment-emergent resistance with the ultra-short BCZD regimen. PRESCIENT will provide rapid evidence for microbiological efficacy as well as key information on safety and clinical treatment outcomes to inform the feasibility and promise of a subsequent phase III treatment-shortening trial. ;

Related Conditions & MeSH terms

• HIV
• Tuberculosis
• Tuberculosis, Pulmonary

• NCT number: NCT05556746
• Study type: Interventional
• Source: Brigham and Women's Hospital
• Contact: Serena Koenig, MD
• Phone: 617-413-4090
• Email: skoenig@bwh.harvard.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: November 24, 2023
• Completion date: January 2027