In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 2 ( 2023-2-2), p. e0278087-
Kurzfassung:
Tuberculosis preventive treatment (TPT) is an essential component for TB elimination. In order to be successfully implemented on a large scale, TPT needs to be safe, affordable and widely available in all settings. Short TPT regimens, that are less burdensome than longer regimens, to patients and health systems, are needed. Doses of rifampin higher than the standard 10mg/kg/day were tolerated in studies to reduce duration of treatment for tuberculosis disease (TBD). The objective of this trial is to test the safety of high dose rifampin monotherapy to shorten the duration of the currently recommended TPT of 4 months rifampin. Methods and analysis This is a phase 2b, randomised, controlled, parallel group, superiority, partially-blind trial. Primary outcomes are completion of treatment (as a proxy measure of tolerability) and safety. The two experimental arms comprise 60 days of (i) 20mg/kg/day or (ii) 30mg/kg/day rifampin; the control arm comprises 120 days of 10mg/kg/day rifampin as TPT. Participants are adults and children 10 years or older, eligible for TPT. Completion is the primary outcome, measured by pill count and is defined as taking minimum of 80% of treatment in 120% of allowed time; it will be tested for superiority by logistic regression. Safety outcome comprises proportion of grade 3–5 adverse events and grade 1–2 rash, adjudicated related to study drug, and resulting in permanent drug discontinuation; compared for non-inferiority between each of the two high dose arms and the standard arm, using Poisson regression. A sample size of 1,359 participants will give 80% power to detect a 10% difference in completion rates and a 1% difference in the safety outcome. The study is conducted in Canada, Indonesia and Vietnam. Enrolment is ongoing at all sites. Ethics and dissemination Approvals from a local research ethics board (REB) have been obtained at all participating sites and by the trial coordinating centre. Approval has been given by drug regulatory agencies in Canada and Indonesia and by Ministry of Health in Vietnam; participants give written informed consent before participation. All data collected are non-nominal. Primary results will be submitted for publication in a peer-reviewed journal when all participants have completed treatment; results of secondary outcomes will be submitted for publication at the end of study; all sites will receive the final data of participants from their sites. Trial registration Trial registered in ClinicalTrials.gov (Identifier: NCT03988933 ). Coordinating center is the study team working at McGill University Health Center-Research Institute (MUHC-RI); sponsor is the MUHC-RI; funding has been granted by Canadian Institute of Health Research (FDN-143350).
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0278087
DOI:
10.1371/journal.pone.0278087.g001
DOI:
10.1371/journal.pone.0278087.t001
DOI:
10.1371/journal.pone.0278087.t002
DOI:
10.1371/journal.pone.0278087.t003
DOI:
10.1371/journal.pone.0278087.t004
DOI:
10.1371/journal.pone.0278087.s001
DOI:
10.1371/journal.pone.0278087.s002
DOI:
10.1371/journal.pone.0278087.s003
DOI:
10.1371/journal.pone.0278087.s004
DOI:
10.1371/journal.pone.0278087.s005
DOI:
10.1371/journal.pone.0278087.s006
DOI:
10.1371/journal.pone.0278087.s007
DOI:
10.1371/journal.pone.0278087.s008
DOI:
10.1371/journal.pone.0278087.s009
DOI:
10.1371/journal.pone.0278087.s010
DOI:
10.1371/journal.pone.0278087.r001
DOI:
10.1371/journal.pone.0278087.r002
DOI:
10.1371/journal.pone.0278087.r003
DOI:
10.1371/journal.pone.0278087.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2267670-3
