Centre for Infection and Immunity, Queen's University of Belfast, Belfast, BT9 7BL, UK.
Trials. 2012 Sep 17;13:170. doi: 10.1186/1745-6215-13-170.
Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.
METHODS/DESIGN: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.
Current Controlled Trials ISRCTN88244364.
急性肺损伤（ALI）是一种常见的破坏性临床综合征，其特征为危及生命的呼吸衰竭，需要机械通气和多器官衰竭。有体外、动物研究和临床前数据表明，他汀类药物可能对 ALI 有益。辛伐他汀治疗急性肺损伤以降低肺功能障碍（HARP-2）试验是一项多中心、前瞻性、随机、分配隐藏、双盲、安慰剂对照临床试验，旨在检验辛伐他汀治疗可改善 ALI 患者临床结局的假设。
方法/设计：符合美国-欧洲共识会议 ALI 定义的患者将以 1:1 的比例随机分为接受肠内辛伐他汀 80mg 或安慰剂组，每天一次，最长 28 天。随机分组将根据招募医院和血管加压药需求进行分层。数据将由参与的 ICU 记录，直至患者出院，并在随机分组后 3、6 和 12 个月进行随访。主要结局是无呼吸机天数至第 28 天。次要结局是：氧合指数和序贯器官衰竭评估评分的变化至第 28 天，非肺部器官衰竭天数至第 28 天，重症监护病房死亡率；医院死亡率；随机分组后 28 天死亡率和随机分组后 12 个月死亡率；出院时的健康相关生活质量，随机分组后 3、6 和 12 个月；重症监护病房和医院住院时间；随机分组后 12 个月的卫生服务使用情况；以及安全性。该试验将从英国和爱尔兰的大约 35 个 ICU 招募 540 名患者。将同时进行经济评估。将在第 28 天采集血浆和尿液样本，以研究辛伐他汀改善临床结局的潜在机制。
当前对照试验 ISRCTN88244364。
