Tuberculosis, Pulmonary Clinical Trial
— TB-PRACTECALOfficial 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
Verified date | April 2024 |
Source | Medecins Sans Frontieres, Netherlands |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 552 |
Est. completion date | August 5, 2022 |
Est. primary completion date | August 5, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 15 Years and older |
Eligibility | Inclusion criteria: 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); Exclusion criteria: 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; - 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. |
Country | Name | City | State |
---|---|---|---|
Belarus | Republican Scientific and Practical Centre for Pulmonology and Tuberculosis hospital | Minsk | |
South Africa | King DinuZulu Hospital | Durban | KwaZulu-Natal |
South Africa | THINK Clinical Trial Unit, Hillcrest | Durban | KwaZulu-Natal |
South Africa | Helen Jospeh Hospital | Johannesburg | Gauteng |
South Africa | Doris Goodwin Hospital | Pietermaritzburg | KwaZulu Natal |
Uzbekistan | Republican TB Hospital No. 2 | Nukus | Karakalpakstan |
Uzbekistan | Sh Alimov Republican Specialised Scientific-Practical Medical Centre for Phthysiology and Pulmonology Hospital | Tashkent |
Lead Sponsor | Collaborator |
---|---|
Medecins Sans Frontieres, Netherlands | Drugs for Neglected Diseases, eResearch Technology, Inc., Global Alliance for TB Drug Development, London School of Hygiene and Tropical Medicine, Ministry of Health, Republic of Uzbekistan, Ministry of Public Health, Republic of Belarus, Rutgers, The State University of New Jersey, Swiss Tropical & Public Health Institute, THINK TB & HIV Investigative Network, University College, London, University of California, San Francisco, University of Liverpool, Wits Health Consortium (Pty) Ltd, World Health Organization |
Belarus, South Africa, Uzbekistan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Stage 1:Percentage of patients with culture conversion in liquid media at 8 weeks post randomisation. | 8 weeks post randomisation | ||
Primary | Stage 1: Percentage of patients who discontinue treatment for any reason or die | 8 weeks post randomisation | ||
Primary | Stage 2: Percentage of patients with an unfavourable outcome (failure, death, recurrence, loss to follow-up) | 72 weeks post-randomisation | ||
Secondary | Stage 1: Percentage of patients with grade 3 or higher QT prolongation | within 8 weeks post randomisation | ||
Secondary | Stage 1: Percentage of patients experiencing at least one Serious Adverse Event (SAE) | within 8 weeks post randomisation | ||
Secondary | Stage 1:Percentage of patients experiencing at least one new grade 3 or higher Adverse Event | within 8 weeks post randomisation | ||
Secondary | Stage 2: Percentage of patients with culture conversion | 12 weeks post randomisation | ||
Secondary | Stage 2: Percentage of patients with an unfavourable outcome (i.e. failure, treatment discontinuation, death, loss to follow up) | 24 weeks post randomisation | ||
Secondary | 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) | 108 weeks post randomisation | ||
Secondary | Stage 2: Median time to culture conversion | 108 weeks | ||
Secondary | Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE | 72 weeks post randomisation | ||
Secondary | Stage 2: Percentage of patients with an SAE or new grade 3 or higher AE | 108 weeks post randomisation | ||
Secondary | 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). | 24 weeks in investigational arms and 108 weeks in SOC arm | |
Secondary | Stage 2: Mean single ?QTcF | 24 weeks post randomisation | ||
Secondary | Stage 2: Percentage of patients experiencing recurrence | week 48 in investigational arms | ||
Secondary | Stage 2: Plasma drug concentrations | In relation to dose intake and start of treatment over a 72 week period | ||
Secondary | Stage 2: TB drug hair levels | In relation to dose intake and start of treatment over a 72 week period |
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