Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.
Telmisartan and Insulin Resistance in HIV (TAILoR): protocol for a dose-ranging phase II randomised open-labelled trial of telmisartan as a strategy for the reduction of insulin resistance in HIV-positive individuals on combination antiretroviral therapy.
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DOI：
10.1136/bmjopen-2015-009566
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发表时间：
2015-10-15
期刊：
影响因子：
2.9
通讯作者：
Pirmohamed M
中科院分区：
文献类型：
--
作者：
Pushpakom SP;Taylor C;Kolamunnage-Dona R;Spowart C;Vora J;García-Fiñana M;Kemp GJ;Whitehead J;Jaki T;Khoo S;Williamson P;Pirmohamed M
替米沙坦是一种血管紧张素受体阻滞剂，对非HIV人群的胰岛素抵抗和心血管健康具有有益作用。本试验将评估替米沙坦是否可以降低接受联合抗逆转录病毒治疗的HIV阳性个体的胰岛素抵抗。这是一项在336名HIV阳性个体中进行的为期48周的替米沙坦II期、多中心、随机化、开放标签、剂量范围探索试验。 该试验将使用适应性设计来确定替米沙坦的最佳剂量。患者最初将按1：1：1：1的比例随机分配接受三种剂量的替米沙坦（20、40和80 mg）之一或不接受干预（对照）。 当计划的最多336例患者中的一半已随访至少24周时，将进行中期分析。 研究的第二阶段将取决于中期分析的结果。主要结局指标是治疗24周后，与非干预组相比，替米沙坦治疗组的胰岛素抵抗降低（通过稳态模型评估-胰岛素抵抗（HOMA-IR）测定） 。次要结局指标包括血脂谱变化、体脂再分布（如通过MRI测量的）;在12、24和48周时心脏代谢和肾脏健康的各种生物标志物的血浆和尿液水平 。将比较不同替米沙坦治疗剂量组和对照组之间的严重不良事件。本研究、本方案和相关文件已获得西北利物浦中心国家研究伦理服务委员会的批准（参考号：12/NW/0214）。成功完成后，研究数据将与学术合作者共享。TAILoR的研究结果将通过同行评审的出版物、科学会议、媒体以及患者和公众的参与进行传播。04196/0024/001-0001; EUDRACT：2012-000935-18; ISRCTN：51069819。
Telmisartan, an angiotensin receptor blocker, has beneficial effects on insulin resistance and cardiovascular health in non-HIV populations. This trial will evaluate whether telmisartan can reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy. This is a phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan in 336 HIV-positive individuals over a period of 48 weeks. The trial will use an adaptive design to inform the optimal dose of telmisartan. Patients will be randomised initially 1:1:1:1 to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). An interim analysis will be performed when half of the planned maximum of 336 patients have been followed up for at least 24 weeks. The second stage of the study will depend on the results of interim analysis. The primary outcome measure is a reduction in insulin resistance (as measured by Homeostatic Model Assessment—Insulin Resistance (HOMA-IR)) in telmisartan treated arm(s) after 24 weeks of treatment in comparison with the non-intervention arm. The secondary outcome measures include changes in lipid profile; body fat redistribution (as measured by MRI); plasma and urinary levels of various biomarkers of cardiometabolic and renal health at 12, 24 and 48 weeks. Serious adverse events will be compared between different telmisartan treated dose arm(s) and the control arm. The study, this protocol and related documents have been approved by the National Research Ethics Service Committee North West—Liverpool Central (Ref: 12/NW/0214). On successful completion, study data will be shared with academic collaborators. The findings from TAILoR will be disseminated through peer-reviewed publications, at scientific conferences, the media and through patient and public involvement. 04196/0024/001-0001; EUDRACT: 2012-000935-18; ISRCTN: 51069819.