Tuberculosis, Multidrug-ResistantPhase 2/3TB-PRACTECALNCT02589782
Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s)
A Phase 2/3 study testing Bedaquiline, Pretomanid and Moxifloxacin in people with Tuberculosis, Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis, run by Medecins Sans Frontieres, Netherlands at 7 sites in 3 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Pulmonary
- What is being tested?
- Bedaquiline, Pretomanid and Moxifloxacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 552 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Jan 2017to 5 Aug 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients eligible for inclusion in the trial must fulfil all of the following criteria:
- Male or female subjects aged 15 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);
Who cannot join
- Patients will not be eligible for inclusion in the trial if they meet any of the following 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;
Show all 21Show fewer
- 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, pretomanid, delamanid or linezolid.
- Prior use of bedaquiline and/or pretomanid and/or linezolid and/or delamanid 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 for more than 2 weeks (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.
- PKPD inclusion/exclusion:
- Adult patients (aged 18 years or above) recruited into the investigational arms of the TB-PRACTECAL trial in the approved sites.
- Willing to sign the sub-study informed consent form after agreeing to the additional blood draws.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
South Africa4 sites
THINK Clinical Trial Unit, Hillcrest
Durban, KwaZulu-Natal, 3650
King DinuZulu Hospital
Durban, KwaZulu-Natal, 4091
Helen Jospeh Hospital
Johannesburg, Gauteng, 2092
Doris Goodwin Hospital
Pietermaritzburg, KwaZulu-Natal
Uzbekistan2 sites
Republican TB Hospital No. 2
Nukus, Karakalpakstan
Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital
Tashkent
Belarus1 site
Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital
Minsk
About this study
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
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).
Read the 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 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.
- Conditions
- Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Pulmonary
- Being tested
- Bedaquiline, Pretomanid, Moxifloxacin, Linezolid, Clofazimine
- Keywords
- bedaquiline, Nitroimidazoles, diarylquinolines, linezolid, clofazimine, pretomanid, moxifloxacin
- Medical subject headings
- Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BedaquilineDrug
Also called Sirturo, R207910, TMC207
PretomanidDrug
Also called PA-824
MoxifloxacinDrug
Also called Avelox
LinezolidDrug
Also called Zyvox
ClofazimineDrug
Also called Lamprene
Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB.Drug
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1 | Experimental | 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 Receives: Drug: Bedaquiline; Drug: Pretomanid; Drug: Moxifloxacin; Drug: Linezolid |
| Regimen 2 | Experimental | 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 Receives: Drug: Bedaquiline; Drug: Pretomanid; Drug: Linezolid; Drug: Clofazimine |
| Regimen 3 | Experimental | 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) Receives: Drug: Bedaquiline; Drug: Pretomanid; Drug: Linezolid |
| Control Regimen | Active comparator | Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB. Receives: Drug: Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1:Percentage of patients with culture conversion in liquid media at 8 weeks post randomisation.
Measured: 8 weeks post randomisation
Stage 1: Percentage of patients who discontinue treatment for any reason or die
Measured: 8 weeks post randomisation
Stage 2: Percentage of patients with an unfavourable outcome (failure, death, recurrence, loss to follow-up)
Measured: 72 weeks post-randomisation
Secondary outcomes (14)
Stage 1: Percentage of patients with grade 3 or higher QT prolongation
Measured: within 8 weeks post randomisation
Stage 1: Percentage of patients experiencing at least one Serious Adverse Event (SAE)
Measured: within 8 weeks post randomisation
Stage 1:Percentage of patients experiencing at least one new grade 3 or higher Adverse Event
Measured: within 8 weeks post randomisation
Stage 2: Percentage of patients with culture conversion
Measured: 12 weeks post randomisation
Stage 2: Percentage of patients with an unfavourable outcome (i.e. failure, treatment discontinuation, death, loss to follow up)
Measured: 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)
Measured: 108 weeks post randomisation
Stage 2: Median time to culture conversion
Measured: 108 weeks
Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE
Measured: 72 weeks post randomisation
Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE
Measured: 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).
Measured: 24 weeks in investigational arms and 108 weeks in SOC arm
Stage 2: Mean single ΔQTcF
Measured: 24 weeks post randomisation
Stage 2: Percentage of patients experiencing recurrence
Measured: week 48 in investigational arms
Stage 2: Plasma drug concentrations
Measured: In relation to dose intake and start of treatment over a 72 week period
Stage 2: TB drug hair levels
Measured: In relation to dose intake and start of treatment over a 72 week period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2015 (estimated)
- Study startJan 2017
- Primary completion5 Aug 2022
- Study completion5 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, Multidrug-ResistantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 552 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medecins Sans Frontieres, Netherlands
- Sponsor type
- University, hospital or other
- 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 Public Health, Republic of Belarus, THINK TB & HIV Investigative Network, University of Liverpool, Wits Health Consortium (Pty) Ltd, Rutgers, The State University of New Jersey, University of California, San Francisco
- Responsible party
- Sponsor
- Investigators
- Bern-Thomas Nyang'wa, MD, Principal investigator, Medecins Sans Frontieres, Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02589782
- Sponsor's protocol ID
- 1541
- Acronym
- TB-PRACTECAL
- Status last verified
- Apr 2024
- First submitted
- 15 Oct 2015
- Last updated
- 1 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Deidentified dataset will be made available via the TB-PACTS repository.
Publications
Motta I, Cusinato M, Ludman AJ, Lachenal N, Dodd M, Soe M, Abdrasuliev T, Usmanova R, Butabekov I, Nikolaevna TZ, Liverko I, Parpieva N, Moodliar R, Solodovnikova V, Kazounis E, Nyang'wa B-T, Fielding KL, Berry C. How much should we still worry about QTc prolongation in rifampicin-resistant tuberculosis? ECG findings from TB-PRACTECAL clinical trial. Antimicrob Agents Chemother. 2024 Jul 9;68(7):e0053624. doi: 10.1128/aac.00536-24. Epub 2024 Jun 6.
PubMed 38842323Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Moodliar R, Dodd M, Solodovnikova V, Liverko I, Rajaram S, Rassool M, McHugh T, Spigelman M, Moore DA, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL team. Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med. 2024 Feb;12(2):117-128. doi: 10.1016/S2213-2600(23)00389-2. Epub 2023 Nov 16.
PubMed 37980911Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166.
PubMed 36546625Berry C, du Cros P, Fielding K, Gajewski S, Kazounis E, McHugh TD, Merle C, Motta I, Moore DAJ, Nyang'wa BT. TB-PRACTECAL: study protocol for 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. Trials. 2022 Jun 13;23(1):484. doi: 10.1186/s13063-022-06331-8.
PubMed 35698158
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02589782
- Acronym / sponsor ID
- TB-PRACTECAL / 1541
- Conditions
- Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Pulmonary
- Keywords
- bedaquiline, Nitroimidazoles, diarylquinolines, linezolid, clofazimine, pretomanid, moxifloxacin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 552 participants (actual)
- Lead sponsor
- Medecins Sans Frontieres, NetherlandsUniversity, hospital or other
- 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 Public Health, Republic of Belarus, THINK TB & HIV Investigative Network, University of Liverpool, Wits Health Consortium (Pty) Ltd, Rutgers, The State University of New Jersey, University of California, San Francisco
- Study start
- Jan 2017 (actual)
- Primary completion
- 5 Aug 2022 (actual)
- Study completion
- 5 Aug 2022 (actual)
- First posted
- 28 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Regimen 1 | Experimental | Drug: Bedaquiline, Drug: Pretomanid, Drug: Moxifloxacin, Drug: LinezolidBedaquiline: 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 |
| Regimen 2 | Experimental | Drug: Bedaquiline, Drug: Pretomanid, Drug: Linezolid, Drug: ClofazimineBedaquiline: 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 |
| Regimen 3 | Experimental | Drug: Bedaquiline, Drug: Pretomanid, Drug: LinezolidBedaquiline: 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) |
| Control Regimen | Active comparator | Drug: Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB.Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female subjects aged 15 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);
Key exclusion criteria (21 listed)
- Patients will not be eligible for inclusion in the trial if they meet any of the following 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BedaquilineAlso: Sirturo, R207910, TMC207 | Drug | Regimen 1, Regimen 2, Regimen 3 |
| PretomanidAlso: PA-824 | Drug | Regimen 1, Regimen 2, Regimen 3 |
| MoxifloxacinAlso: Avelox | Drug | Regimen 1 |
| LinezolidAlso: Zyvox | Drug | Regimen 1, Regimen 2, Regimen 3 |
| ClofazimineAlso: Lamprene | Drug | Regimen 2 |
| Locally accepted standard of care which is consistent with the WHO recommendations for the treatment of M/XDR-TB. | Drug | Control Regimen |
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
14 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2024.
- Derived from this study: PubMed 38842323Motta I, Cusinato M, Ludman AJ, Lachenal N, Dodd M, Soe M, Abdrasuliev T, Usmanova R, Butabekov I, Nikolaevna TZ, Liverko I, Parpieva N, Moodliar R, Solodovnikova V, Kazounis E, Nyang'wa B-T, Fielding KL, Berry C. How much should we still worry about QTc prolongation in rifampicin-resistant tuberculosis? ECG findings from TB-PRACTECAL clinical trial. Antimicrob Agents Chemother. 2024 Jul 9;68(7):e0053624. doi: 10.1128/aac.00536-24. Epub 2024 Jun 6.
- Derived from this study: PubMed 37980911Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Moodliar R, Dodd M, Solodovnikova V, Liverko I, Rajaram S, Rassool M, McHugh T, Spigelman M, Moore DA, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL team. Short oral regimens for pulmonary rifampicin-resistant tuberculosis (TB-PRACTECAL): an open-label, randomised, controlled, phase 2B-3, multi-arm, multicentre, non-inferiority trial. Lancet Respir Med. 2024 Feb;12(2):117-128. doi: 10.1016/S2213-2600(23)00389-2. Epub 2023 Nov 16.
- Derived from this study: PubMed 36546625Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166.
- Derived from this study: PubMed 35698158Berry C, du Cros P, Fielding K, Gajewski S, Kazounis E, McHugh TD, Merle C, Motta I, Moore DAJ, Nyang'wa BT. TB-PRACTECAL: study protocol for 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. Trials. 2022 Jun 13;23(1):484. doi: 10.1186/s13063-022-06331-8.
- Individual participant dataSharing planned: Yes. Deidentified dataset will be made available via the TB-PACTS repository.
Related trials for Tuberculosis, Multidrug-Resistant
RecruitingObservational study
Training Protocol on the Natural History of Tuberculosis
Mycobacterium Infections, Tuberculosis, Multidrug-Resistant
RecruitingObservational study
Molecular Epidemiology, Strains Genotyping of Multi-drug Resistant Tuberculosis Circulating in Central Africa Region
Multidrug-resistant Tuberculosis (MDR-TB)
RecruitingPhase 3
A Study of Quabodepistat-containing Regimens for the Treatment of Drug-resistant Pulmonary Tuberculosis
Rifampicin-Resistant Pulmonary Tuberculosis, Multidrug-Resistant Pulmonary Tuberculosis
Recruiting
Bring BPaL2Me Trial Comparing Nurse-Led RR-TB Treatment to Physician-Led RR-TB Treatment
Drug Resistant Tuberculosis
RecruitingObservational study
Bioneer Q-RFIA Clinical Evaluation
Tuberculosis, Multidrug-Resistant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bern-Thomas Nyang'wa, MD principal investigator
Medecins Sans Frontieres, Netherlands
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bedaquiline, Pretomanid and Moxifloxacin in people with Tuberculosis, Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis, run by Medecins Sans Frontieres, Netherlands at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in South Africa, Uzbekistan, Belarus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1:Percentage of patients with culture conversion in liquid media at 8 weeks post randomisation. (time frame: 8 weeks post randomisation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02589782, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2024.