An observational study in Multi-drug Resistant Tuberculosis, sponsored by University of Cape Town. Status unknown at 7 sites in 6 countries. Open to participants aged 15 Years to 99 Years. Per ClinicalTrials.gov, last updated 2022-11-04.
Sponsored by University of Cape Town · Observational
PandrTB is a study of the pharmacokinetics(PK) and pharmacodynamics(PD) of bedaquiline, delamanid, clofazimine, linezolid, moxifloxacin, levofloxacin and pyrazinamide used in novel combinations to treat multidrug-resistant tuberculosis(MDR-TB).
PandrTB is an observational study nested in the endTB (a randomized study that will evaluate five 9-month, injectable-sparing regimens) and endTB-Q (and RCT evaluating a 4 drug oral regimen given for 6 or 9 months) trials. These trials are providing evidence to support the transformation of MDR-TB treatment. As part of PandrTB: the plasma concentrations of the experimental arm drugs (the new and repurposed drugs bedaquiline, delamanid, clofazimine and linezolid, as well as levofloxacin, moxifloxacin and pyrazinamide) will be measured; MICs will be determined in baseline isolates; and MGIT cultures, additional to those in the endTB study, will be performed at weeks 6 and 10. Nonlinear mixed-effects models will describe the population PK of the drugs and a pharmacodynamic (PD) model of treatment response of Mycobacterium tuberculosis(Mtb) load over time. Recursive partitioning methods will evaluate baseline MICs and PK measures as drivers of treatment response (as described by the parameters of the PD model of initial treatment response of Mtb load over time, and the endTB trial endpoints: time to culture conversion, longer-term outcomes, and acquisition of phenotypic resistance). Thus the key drugs and plasma drug exposure thresholds for activity will be defined, and exposure-dependent synergy or antagonism identified. The risks of toxicities (as assessed in the endTB study) will be estimated, by plasma drug exposure and important comorbidity (including HIV infection). In this way, the PK-efficacy and PK-toxicity analyses will allow definition of target plasma drug exposures. Simulations will predict optimal doses. To advance the understanding of drug penetration, we will develop approaches to measure free drug plasma concentrations. Drug-drug interactions will be described. Thus PandrTB will inform how best to use these new and repurposed drugs in combination, to create the most effective and least toxic regimens while minimizing the development of further drug resistance.
132 studies on the registry are indexed under Tuberculosis, Multidrug-Resistant; 25 are open to participants now.
This study's planned enrollment of 625 is above the median of 410 across 42 observational studies indexed under Tuberculosis, Multidrug-Resistant.
Browse Tuberculosis, Multidrug-Resistant studies →University of Cape Town is the lead sponsor of 116 studies on the registry; 14 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adults and adolescents (≥15 years) will be enrolled. There is increasing recognition that adolescents have been neglected in the development of treatments for diseases like HIV and TB, given that they comprise and important population. Minors are included in the endTB clinical trial and it would be wrong to exclude them from a PK study designed to optimize doses.
All patients enrolled to the experimental arms of the endTB study and provide their written to participate in the PandrTB study.
Exclusion Criteria:
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Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
endTB and endTB-Q study participants on experimental regimen
Drug exposure (AUC)
drug exposures derived using population PK models
Time frame: 5 years
Rate of decline of viable M.tubercolosis in sputum
A pharmacodynamic biomarker model of response to treatment will be used to derive the rate of decline of Mtb in MIGT cultures. The effect of PK on this measure will be evaluated.
Time frame: 5 years
Collecting adverse events as a measure of safety
The effect of pharmacokinetics on drug and regimen saftey will be evaluated using recursive partitioning methods.
Time frame: 5 years
Plan to share: Undecided
Started Jan 2020 (actual). Primary completion is estimated for Apr 2023, 39 months after the start.
Of 19 observational studies under Tuberculosis, Multidrug-Resistant, half reached primary completion within 53 months of starting (the median), counting those still running; a quarter within 32 and three quarters within 90. This study's planned 39 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
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