Clinical Trial: Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomised, Controlled, Open-Label, Phase II-III Trial to Evaluate the Safety and Efficacy of Regimens Containing Bedaquiline and Pretomanid for the Treatment of Adult Patients With Pulmonary Multid

Brief Summary: 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).

Detailed Summary:

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 a
Sponsor: Medecins Sans Frontieres, Netherlands

Current Primary Outcome:

  • 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 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 [ Time Frame: 24 weeks in investigational arms and 108 weeks in SOC arm ]
    We will evaluate 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).
  • 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 ]


Original Secondary Outcome: Same as current

Information By: Medecins Sans Frontieres, Netherlands

Dates:
Date Received: October 15, 2015
Date Started: January 2017
Date Completion: March 2021
Last Updated: January 16, 2017
Last Verified: January 2017