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Trial record 26 of 33 for:    bedaquiline

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

This study is currently recruiting participants.
See Contacts and Locations
Verified January 2017 by Medecins Sans Frontieres, Netherlands
Sponsor:
Collaborators:
London School of Hygiene and Tropical Medicine
Global Alliance for TB Drug Development
University College, London
Drugs for Neglected Diseases
Swiss Tropical & Public Health Institute
eResearch Technology, Inc.
Ministry of Health, Republic of Uzbekistan
World Health Organization
Ministry of Health, Belarus
TB & HIV Investigative Network (THINK)
Information provided by (Responsible Party):
Medecins Sans Frontieres, Netherlands
ClinicalTrials.gov Identifier:
NCT02589782
First received: October 15, 2015
Last updated: January 16, 2017
Last verified: January 2017
  Purpose
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).

Condition Intervention Phase
Tuberculosis, Multidrug-Resistant Extensively Drug-Resistant Tuberculosis Tuberculosis, Pulmonary Drug: Bedaquiline Drug: Pretomanid Drug: Moxifloxacin Drug: Linezolid Drug: Clofazimine Drug: Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB. Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Multidrug Resistant Tuberculosis

Resource links provided by NLM:


Further study details as provided by Medecins Sans Frontieres, Netherlands:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 630
Study Start Date: January 2017
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1
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
Other Names:
  • Sirturo
  • R207910
  • TMC207
Drug: Pretomanid
Other Name: PA-824
Drug: Moxifloxacin
Other Name: Avelox
Drug: Linezolid
Other Name: Zyvox
Experimental: Regimen 2
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
Other Names:
  • Sirturo
  • R207910
  • TMC207
Drug: Pretomanid
Other Name: PA-824
Drug: Linezolid
Other Name: Zyvox
Drug: Clofazimine
Other Name: Lamprene
Experimental: Regimen 3
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
Other Names:
  • Sirturo
  • R207910
  • TMC207
Drug: Pretomanid
Other Name: PA-824
Drug: Linezolid
Other Name: Zyvox
Active Comparator: Control Regimen
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.

Detailed Description:

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 two 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 2 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects aged 18 years of age or above, regardless of HIV status;
  • Microbiological test (molecular or phenotypic) confirming presence of M. tuberculosis;
  • Resistant to at least rifampicin by either molecular or phenotypic drug susceptibility test;
  • Completed informed consent form (ICF);
  • Willingness to be hospitalised for the first 8 weeks (stage 1 only)

Exclusion Criteria:

  • Known allergies, hypersensitivity, or intolerance to any of the study drugs;
  • Pregnant or breast-feeding; or unwilling to use appropriate contraceptive measures
  • Liver enzymes >3 times the upper limit of normal (AST or ALT);
  • Any condition (social or medical) which, in the opinion of the investigator, would make study participation unsafe;
  • Taking any medications contraindicated with the medicines in the trial;
  • QTcF > 450ms;
  • One or more risk factors for QT prolongation (excluding age and gender) or other uncorrected risk factors for TdP;
  • History of cardiac disease, syncopal episodes, symptomatic or asymptomatic arrhythmias (with the exception of sinus arrhythmia);
  • Any baseline biochemical laboratory value consistent with Grade 4 toxicity.
  • Moribund
  • Known resistance to bedaquiline or to pretomanid.
  • Participants will be withdrawn secondarily if baseline sputum culture is negative or RR-TB is not confirmed by a phenotypic DST.
  • Prior use of bedaquiline and/or pretomanid and/or linezolid for one or more months.
  • Patients not eligible to start a new course of MDR-TB/XDR-TB treatment according to local protocol, including but not limited to: currently on MDR-TB treatment (and not failing); unstable address; loss to follow-up in previous treatment with no change in circumstance and motivation.
  • Tuberculous meningoencephalitis, brain abscesses, osteomyelitis or arthritis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02589782

Contacts
Contact: Kristen LeBeau +44 2070674255 kristen.lebeau@london.msf.org

Locations
Belarus
Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital Not yet recruiting
Minsk, Belarus
Contact: Animesh Sinha, MD       minsk-ct-mtl@oca.msf.org   
Principal Investigator: Alena Skrahina, MD         
South Africa
Doris Goodwin Hospital Not yet recruiting
Pietermaritzburg, KwaZulu Natal, South Africa
Contact: Suzanne Staples       s.staples@thinksa.org.za   
Principal Investigator: Suzanne Staples, MD         
Don McKenzie Hospital Not yet recruiting
Durban, KwaZulu-Natal, South Africa
Contact: Suzanne Staples       s.staples@thinksa.org.za   
Principal Investigator: Suzanne Staples, MD         
Uzbekistan
Republican TB Hospital No. 2 Recruiting
Nukus, Karakalpakstan, Uzbekistan
Contact: Monica Moschioni, PhD       NukusCT-crc@oca.msf.org   
Principal Investigator: Tigay N Zinaida, MD         
Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital Not yet recruiting
Tashkent, Uzbekistan
Contact: Viktoria Prymaka         
Principal Investigator: Irina Liverko, MD         
Sponsors and Collaborators
Medecins Sans Frontieres, Netherlands
London School of Hygiene and Tropical Medicine
Global Alliance for TB Drug Development
University College, London
Drugs for Neglected Diseases
Swiss Tropical & Public Health Institute
eResearch Technology, Inc.
Ministry of Health, Republic of Uzbekistan
World Health Organization
Ministry of Health, Belarus
TB & HIV Investigative Network (THINK)
Investigators
Principal Investigator: Bern-Thomas Nyang'wa, MD Medecins Sans Frontieres, Netherlands
  More Information

Responsible Party: Medecins Sans Frontieres, Netherlands
ClinicalTrials.gov Identifier: NCT02589782     History of Changes
Other Study ID Numbers: 1541
Study First Received: October 15, 2015
Last Updated: January 16, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Medecins Sans Frontieres, Netherlands:
bedaquiline
Nitroimidazoles
diarylquinolines
linezolid
clofazimine
pretomanid
moxifloxacin

Additional relevant MeSH terms:
Bedaquiline
Tuberculosis
Tuberculosis, Multidrug-Resistant
Tuberculosis, Pulmonary
Extensively Drug-Resistant Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Moxifloxacin
Fluoroquinolones
Linezolid
Clofazimine
Diarylquinolines
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 21, 2017