Crit Care Med. 2002 Jan;30(1):1-6. doi: 10.1097/00003246-200201000-00001.
To determine whether the administration of lisofylline (1-[5R-hydroxyhexyl]-3,7-dimethylxanthine) would decrease mortality in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).
A prospective, randomized, double-blind, placebo-controlled, multicenter study.
Intensive care units at 21 hospitals at the ten centers constituting the ARDS Clinical Trials Network.
A total of 235 patients who met eligibility criteria were enrolled in the study (116 into the lisofylline group, 119 into the placebo group).
Patients were randomized to receive either lisofylline or placebo. The dose of lisofylline was 3 mg/kg with a maximum dose of 300 mg intravenously every 6 hrs. The intravenous solution of study drug was administered over 10 mins every 6 hrs. Dosing was continued for 20 days or until the patient achieved 48 hrs of unassisted breathing.
The trial was stopped by the Data Safety Monitoring Board for futility at the first scheduled interim analysis. The patient groups had similar characteristics at enrollment. No significant safety concerns were associated with lisofylline therapy. There was no significant difference between groups in the number of patients who had died at 28 days (31.9% lisofylline vs. 24.7% placebo, p = .215). There was no significant difference between the lisofylline and placebo groups in terms of resolution of organ failures, ventilator-free days, infection-related deaths, or development of serious infection during the 28-day study period. The median number of organ failure-free days for the five nonpulmonary organ failures examined (cardiovascular, central nervous system, coagulation, hepatic, and renal) was not different between the lisofylline and placebo groups. Although lisofylline has been reported to decrease circulating free fatty acid levels, we did not find any such treatment effect compared with placebo.
In this study, there was no evidence that lisofylline had beneficial effects in the treatment of established ALI/ARDS.
确定给予利索茶碱（1-[5R-羟基己基]-3,7-二甲基黄嘌呤）是否会降低急性肺损伤（ALI）或急性呼吸窘迫综合征（ARDS）患者的死亡率。
一项前瞻性、随机、双盲、安慰剂对照、多中心研究。
构成ARDS临床试验网络的十个中心的21家医院的重症监护病房。
共有235名符合入选标准的患者被纳入研究（116名进入利索茶碱组，119名进入安慰剂组）。
患者被随机分配接受利索茶碱或安慰剂。利索茶碱的剂量为3mg/kg，最大剂量为300mg，每6小时静脉注射一次。研究药物的静脉溶液每6小时在10分钟内输注完毕。给药持续20天或直至患者实现48小时自主呼吸。
在首次预定的中期分析时，数据安全监测委员会因无效性而停止了该试验。入组时患者组具有相似的特征。利索茶碱治疗未发现重大安全问题。28天时死亡患者数量在两组之间无显著差异（利索茶碱组为31.9%，安慰剂组为24.7%，p = 0.215）。在28天的研究期间，利索茶碱组和安慰剂组在器官功能衰竭的缓解、无呼吸机天数、感染相关死亡或严重感染的发生方面无显著差异。所检查的五个非肺部器官衰竭（心血管、中枢神经系统、凝血、肝脏和肾脏）的无器官衰竭天数中位数在利索茶碱组和安慰剂组之间无差异。尽管据报道利索茶碱可降低循环游离脂肪酸水平，但与安慰剂相比，我们未发现任何此类治疗效果。
在本研究中，没有证据表明利索茶碱对已确诊的ALI/ARDS治疗有有益作用。
