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QT prolongation in the STREAM Stage 1 Trial
G Hughes1, H Bern1, C-Y Chiang2
1Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology, London, UK.
Summary
A shortened regimen for multidrug-resistant tuberculosis (MDR-TB) caused severe QT prolongation in one-third of patients. Risk factors included higher baseline QTcF and origin from Mongolia, impacting treatment implementation.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- The Standardized Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB (STREAM) Stage 1 trial showed a shortened regimen for rifampicin-resistant TB (RR-TB) was non-inferior in efficacy.
- This shortened regimen includes moxifloxacin and clofazimine, drugs associated with QT prolongation, with severe prolongation observed more frequently than in the standard regimen.
Purpose of the Study:
- To investigate risk factors associated with severe QT prolongation in patients receiving the shortened regimen for RR-TB.
Main Methods:
- Analysis of data from 282 patients on the shortened regimen.
- Identification of risk factors for severe QT prolongation, defined as QT/QTcF ≥500 ms or an increase of ≥60 ms from baseline.
Main Results:
- 33.3% (94/282) of patients developed severe QT prolongation.
- Severe QT prolongation (≥500 ms) was significantly more common in patients from Mongolia (45.5%) compared to other sites (3.5-11.9%).
- A higher baseline QTcF (≥400 ms) was a significant risk factor for developing QT/QTcF ≥500 ms (OR 5.99).
Conclusions:
- One-third of patients on the shortened RR-TB regimen experienced severe QT prolongation.
- Geographic location (Mongolia) and higher baseline QTcF are key risk factors for severe QT prolongation.
- Findings have implications for the clinical implementation and monitoring of this shortened TB treatment regimen.
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