Investigation of the efficacy of the short regimen for rifampicin-resistant TB from the STREAM trial.
Investigation of the efficacy of the short regimen for rifampicin-resistant TB from the STREAM trial.
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STREAM 试验研究短疗程治疗利福平耐药结核病的疗效。
DOI：
10.1186/s12916-020-01770-z
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发表时间：
2020-11-04
期刊：
影响因子：
9.3
通讯作者：
Nunn AJ
中科院分区：
文献类型：
--
作者：
Phillips PPJ;Van Deun A;Ahmed S;Goodall RL;Meredith SK;Conradie F;Chiang CY;Rusen ID;Nunn AJ
STREAM 试验表明，对于治疗利福平耐药结核病，9-11 个月的“短”疗法与 20 个月以上的“长”疗法相比，疗效不逊色，且安全性相当。复合主要结果成分的不平衡值得进一步研究。首先，STREAM 主要成果被映射到当前使用的替代方案，包括世卫组织规划成果定义和最近为规划或研究目的提出的其他修改。其次，根据李克特 5 点量表中失败或复发 (FoR) 事件的可能性对结果进行了重新分类：确定、可能、可能、不太可能和极不可能。采用敏感性分析来探讨信息审查的影响。所有分析均使用方案定义的改良意向治疗 (MITT) 分析人群。短期治疗方案的五种替代结果的治愈率从 75.1% 到 84.2% 不等。然而，方案间结果支持长方案的比例不超过 1.3%（95% CI 上限 10.1%），与试验的主要疗效结果相似。仅考虑确定或可能的 FoR 事件，有微弱的证据表明短疗程中 FoR 的风险较高，HR 2.19 (95% CI 0.90, 5.35)，p = 0.076；仅考虑确定的 FoR 事件，证据更强，HR 3.53 (95%CI 1.05, 11.87)，p = 0.030。 3-4 级 AE 的累积数量是审查的最强预测因子。考虑到信息审查的更大影响减弱了治疗差异，尽管 95% CI 非常宽。五种替代结果定义给出了相似的总体结果。短期治疗方案的失败或复发 (FoR) 风险可能高于长期治疗方案，这凸显了在分析中如何解释失访和其他审查的重要性。 FoR 时间的结果应被视为未来药物敏感和耐药结核病治疗试验的主要结果，前提是还包括探索偏离独立审查影响的敏感性分析。
The STREAM trial demonstrated that a 9–11-month “short” regimen had non-inferior efficacy and comparable safety to a 20+ month “long” regimen for the treatment of rifampicin-resistant tuberculosis. Imbalance in the components of the composite primary outcome merited further investigation. Firstly, the STREAM primary outcomes were mapped to alternatives in current use, including WHO programmatic outcome definitions and other recently proposed modifications for programmatic or research purposes. Secondly, the outcomes were re-classified according to the likelihood that it was a Failure or Relapse (FoR) event on a 5-point Likert scale: Definite, Probable, Possible, Unlikely, and Highly Unlikely. Sensitivity analyses were employed to explore the impact of informative censoring. The protocol-defined modified intention-to-treat (MITT) analysis population was used for all analyses. Cure on the short regimen ranged from 75.1 to 84.2% across five alternative outcomes. However, between-regimens results did not exceed 1.3% in favor of the long regimen (95% CI upper bound 10.1%), similar to the primary efficacy results from the trial. Considering only Definite or Probable FoR events, there was weak evidence of a higher risk of FoR in the short regimen, HR 2.19 (95%CI 0.90, 5.35), p = 0.076; considering only Definite FoR events, the evidence was stronger, HR 3.53 (95%CI 1.05, 11.87), p = 0.030. Cumulative number of grade 3–4 AEs was the strongest predictor of censoring. Considering a larger effect of informative censoring attenuated treatment differences, although 95% CI were very wide. Five alternative outcome definitions gave similar overall results. The risk of failure or relapse (FoR) may be higher in the short regimen than in the long regimen, highlighting the importance of how loss to follow-up and other censoring is accounted for in analyses. The outcome of time to FoR should be considered as a primary outcome for future drug-sensitive and drug-resistant TB treatment trials, provided sensitivity analyses exploring the impact of departures from independent censoring are also included.
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影响因子：
2.3
作者：
Dodd S;Williamson P;White IR
通讯作者：
White IR
DOI：
10.1016/0041-3879(80)90002-1
发表时间：
1980-01-01
期刊：
TUBERCLE
影响因子：
--
作者：
MITCHISON, DA;KEYES, AB;NUNN, AJ
通讯作者：
NUNN, AJ
影响因子：
2.5
作者：
Nunn AJ;Rusen ID;Van Deun A;Torrea G;Phillips PP;Chiang CY;Squire SB;Madan J;Meredith SK
通讯作者：
Meredith SK
影响因子：
24.3
作者：
Abidi, Syed;Achar, Jay;Khan, Faiz Ahmad
通讯作者：
Khan, Faiz Ahmad
影响因子：
158.5
作者：
Nunn, Andrew J.;Phillips, Patrick P. J.;Rusen, I. D.
通讯作者：
Rusen, I. D.