The Frequency and Incidence of QT Prolongation With Extended Use of Bedaquiline or Delamanid in a Large, Multi-Country Multidrug-Resistant/Rifampicin-Resistant Tuberculosis Cohort
Bibliographic record
Abstract
BACKGROUND: The 2022 World Health Organization (WHO) guidelines on multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) recommend 6 months of bedaquiline (Bdq) in the all-oral 9-month shorter regimen and 6 months or longer for Bdq and delamanid (Dlm) in the 18-20-month longer regimen. However, lack of evidence on extended treatment using Bdq or Dlm has limited their use to 6 months. We examine the frequency and incidence of QT prolongation based on duration of Bdq and/or Dlm use in longer regimens. METHODS: We analyzed a prospective cohort of MDR/RR-TB patients from 16 countries who initiated treatment with Bdq and/or Dlm containing regimens from 1 April 2015 to 30 September 2018. Data were systematically collected using a shared protocol. The outcome of interest was the first clinically relevant prolonged QT interval (grade 3 or above) or a serious adverse event (SAE) involving prolonged QT of any grade. RESULTS: Among 2553 patients, 59% received >6 months of Bdq and/or Dlm. Of these, 579 (20.9%) patients experienced a prolonged QT event, the majority (95.5%) being grade 1 or 2. Sixty-four (2.5%) patients experienced the outcome of interest with only 12 (0.5%) having ≥1 QT prolonging drugs permanently suspended. The incidence rate of the first prolonged QT event was highest in the first six months of treatment and lower in subsequent 6-month periods. CONCLUSIONS: We demonstrate that Bdq and/or Dlm use beyond 6 months is safe in longer MDR/RR-TB regimens with most clinically relevant QT prolongation events occurring in the first 6 months. Electrocardiogram (ECG) monitoring for early identification of QT prolongating events is possible in programmatic conditions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".