Hughes G, Bern H, Chiang C-Y, Goodall R L, Nunn A J, Rusen I D, Meredith S K
Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials and Methodology, London, UK.
Division of Pulmonary Medicine, Department of Internal Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan, Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, International Union against Tuberculosis and Lung Disease (The Union), Paris, France.
Int J Tuberc Lung Dis. 2022 Nov 1;26(11):1065-1070. doi: 10.5588/ijtld.22.0063.
STREAM (Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) Stage 1 was a randomised trial of a Short (9-month) regimen for rifampicin-resistant TB (RR-TB). QT or QTcF prolongation ≥500 ms occurred in 31 (11%) of 282 Short regimen participants. The frequent ECG monitoring employed might be challenging for treatment programmes. This analysis aimed to determine whether those at higher risk of severe QT prolongation could be identified early for more targeted monitoring. Data from the first month of treatment were used to investigate whether participants were at risk of developing QT/QTcF ≥500 ms. QTcF increases from baseline at different time points were examined. Absolute QTcF measurements were categorised in 5 ms increments at each time-point. The most discriminating time points and QTcF cut-offs were combined to optimise sensitivity and specificity. Absolute QTcF values were more discriminating than magnitude of increase from baseline. More participants who developed QT/QTcF ≥500 ms had a QTcF of respectively ≥425 ms and ≥430 ms at 4 h and Week 3 ( < 0.05) than those who did not. By combining QTcF values ≥425 ms at 4 h and ≥430 ms at Week 3, we identified high-risk participants with 97% sensitivity and 99% negative predictive value. Reduced ECG monitoring may be possible for many Short regimen participants.
STREAM（耐多药结核病患者抗结核药物标准化治疗方案）第一阶段是一项针对利福平耐药结核病（RR-TB）的短期（9个月）治疗方案的随机试验。在282名接受短期治疗方案的参与者中，有31名（11%）出现QT或QTcF延长≥500毫秒。所采用的频繁心电图监测可能对治疗方案构成挑战。该分析旨在确定是否可以早期识别出严重QT延长风险较高的患者，以便进行更有针对性的监测。使用治疗第一个月的数据来调查参与者是否有发生QT/QTcF≥500毫秒的风险。检查了不同时间点QTcF相对于基线的增加情况。在每个时间点，将绝对QTcF测量值以5毫秒的增量进行分类。结合最具区分性的时间点和QTcF临界值，以优化敏感性和特异性。绝对QTcF值比相对于基线的增加幅度更具区分性。与未出现QT/QTcF≥500毫秒的参与者相比，出现该情况的参与者在4小时和第3周时QTcF分别≥425毫秒和≥430毫秒的人数更多（P<0.05）。通过结合4小时时QTcF≥425毫秒和第3周时QTcF≥430毫秒的值，我们识别出高危参与者的敏感性为97%，阴性预测值为99%。对于许多接受短期治疗方案的参与者来说，可能可以减少心电图监测。
