A Phase 2/3 interventional study of Bedaquiline and Pretomanid in Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis and Tuberculosis, Pulmonary, sponsored by Medecins Sans Frontieres, Netherlands. Completed at 7 sites in 3 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2024-05-01.
Sponsored by Medecins Sans Frontieres, Netherlands · Phase 2/3, Interventional, and Treatment
TB PRACTECAL is a multi-centre, open label, multi-arm, randomised, controlled, phase II-III trial; evaluating short treatment regimens containing bedaquiline and pretomanid in combination with existing and re-purposed anti-TB drugs for the treatment of biologically confirmed pulmonary multi drug-resistant TB (MDR-TB).
This is a multi-centre, open label, multi-arm, randomised, controlled, phase II-III trial; evaluating short treatment regimens containing bedaquiline and pretomanid in combination with existing and re-purposed anti-TB drugs for the treatment of biologically confirmed pulmonary multidrug-resistant TB (MDR-TB).
The study will be divided into two stages, with a seamless transition between the stages, meaning recruitment into an arm will only stop after a decision has been taken following stage 1 primary end point data analysis. All recruited patients will be followed up to 108 weeks post randomisation unless they die or withdraw consent. The local standard of care (SOC) MDR-TB regimen will be used as the internal control for both safety and efficacy.
The first stage corresponds to a Phase II trial of safety and preliminary efficacy in patients with MDR-TB. Patients will be recruited into 3 parallel B and Pa containing regimen arms plus a SOC control. The main objective of Stage 1 is to select drug regimens for evaluation in Stage 2 based on 8 week safety and efficacy endpoints. All stage 1 patients will be hospitalised for 8 weeks for intensive cardiological evaluations to establish the QT-specific liability of the regimens.
Investigational arms that do not meet predefined safety and efficacy criteria (percentage culture conversion >40%; percentage discontinuation and death \<45%) will not be considered for further evaluation. The regimens that do not meet these pre-defined safety and/or efficacy criteria will be eligible to be evaluated for long term safety, tolerability and efficacy in Stage 2.
If less than two investigational arms are available for stage two assessment, the SAC will make recommendations on whether new arms should be introduced in the study. If more than two arms are available for the Stage 2 assessment, two regimens will be chosen. The SAC will make recommendations on which arms to take forward to the trial steering committee.
The second stage corresponds to a phase III trial. Patients in this stage will be recruited into the arms chosen from stage 1 plus the SOC. The regimens will primarily be evaluated for safety and efficacy in comparison with the SOC arm at 72 weeks post randomisation. The primary efficacy outcome will be a composite endpoint of the percentage of unfavourable outcomes. The secondary outcomes will include safety outcomes and in particular the percentage of Grade 3 or 4 AEs and SAEs in the investigational regimens compared with the SOC.
1,417 studies on the registry are indexed under Tuberculosis; 208 are open to participants now.
This study's enrollment of 552 is above the median of 150 across 952 interventional studies indexed under Tuberculosis.
Browse Tuberculosis studies →Medecins Sans Frontieres, Netherlands is the lead sponsor of 15 studies on the registry; 1 is open to participants now.
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Patients eligible for inclusion in the trial must fulfil all of the following criteria:
Exclusion criteria:
Patients will not be eligible for inclusion in the trial if they meet any of the following criteria:
Patients not eligible to start a new course of MDR-TB/XDR-TB treatment according to local protocol, including but not limited to:
PKPD inclusion/exclusion:
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Moxifloxacin: 400 mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated
Drug: Bedaquiline · Drug: Pretomanid · Drug: Moxifloxacin · Drug: Linezolid
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated Clofazimine: 50 mg (less than 33 kg), 100 mg (more than 33 kg) for 24 weeks
Drug: Bedaquiline · Drug: Pretomanid · Drug: Linezolid · Drug: Clofazimine
Bedaquiline: 400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks Pretomanid: 200mg once daily for 24 weeks Linezolid: 600mg daily for 16 weeks then 300mg daily (or 600mg x3/wk) for the remaining 8 weeks or earlier when moderately tolerated)
Drug: Bedaquiline · Drug: Pretomanid · Drug: Linezolid
Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB.
Drug: Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB.
Also known as: Sirturo, R207910, TMC207
Also known as: PA-824
Also known as: Avelox
Also known as: Zyvox
Also known as: Lamprene
Stage 1:Percentage of patients with culture conversion in liquid media at 8 weeks post randomisation.
Time frame: 8 weeks post randomisation
Stage 1: Percentage of patients who discontinue treatment for any reason or die
Time frame: 8 weeks post randomisation
Stage 2: Percentage of patients with an unfavourable outcome (failure, death, recurrence, loss to follow-up)
Time frame: 72 weeks post-randomisation
Stage 1: Percentage of patients with grade 3 or higher QT prolongation
Time frame: within 8 weeks post randomisation
Stage 1: Percentage of patients experiencing at least one Serious Adverse Event (SAE)
Time frame: within 8 weeks post randomisation
Stage 1:Percentage of patients experiencing at least one new grade 3 or higher Adverse Event
Time frame: within 8 weeks post randomisation
Stage 2: Percentage of patients with culture conversion
Time frame: 12 weeks post randomisation
Stage 2: Percentage of patients with an unfavourable outcome (i.e. failure, treatment discontinuation, death, loss to follow up)
Time frame: 24 weeks post randomisation
Stage 2: Percentage of patients with an unfavourable outcome (i.e. failure, treatment discontinuation, death, loss to follow up, still on treatment at censure and recurrence)
Time frame: 108 weeks post randomisation
Stage 2: Median time to culture conversion
Time frame: 108 weeks
Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE
Time frame: 72 weeks post randomisation
Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE
Time frame: 108 weeks post randomisation
Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE at the end of treatment
The percentage of patients with an SAE or new grade 3 or higher AE at the end of treatment in the investigational arms (maximum of 24 weeks) and the SOC arm which varies in length (maximum 108 weeks).
Time frame: 24 weeks in investigational arms and 108 weeks in SOC arm
Stage 2: Mean single ΔQTcF
Time frame: 24 weeks post randomisation
Stage 2: Percentage of patients experiencing recurrence
Time frame: week 48 in investigational arms
Stage 2: Plasma drug concentrations
Time frame: In relation to dose intake and start of treatment over a 72 week period
Stage 2: TB drug hair levels
Time frame: In relation to dose intake and start of treatment over a 72 week period
Plan to share: Yes — Deidentified dataset will be made available via the TB-PACTS repository.
Supporting information: Study protocol, Sap
This study is completed, as verified in Apr 2024. You cannot join it, but the record below documents what was studied.
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Medecins Sans Frontieres, Netherlands