Overview

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

Status:
Active, not recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Medecins Sans Frontieres, Netherlands
Collaborators:
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 Health, Swaziland
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
Treatments:
Bedaquiline
Clofazimine
Diarylquinolines
Fluoroquinolones
Linezolid
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Criteria
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.