院外心脏骤停的存活率在过去的几十年里显著上升,但神经学结果仅略有改善。尽管研究了20多种涉及心脏骤停后昏迷患者的神经保护策略,没有人表现出明确的疗效证据;然而,在心脏骤停的实验模型中,用酰基-ghrelin治疗显示出改善的功能和组织学脑恢复,并且在各种人类研究人群中是安全的。
■确定静脉注射酰基生长素释放肽改善心脏骤停后昏迷患者神经系统预后的安全性和潜在疗效。
■第二阶段,双盲,安慰剂对照,多中心,随机临床试验,Ghrelin治疗心脏骤停后昏迷患者:促进大脑恢复的临床试验(GRECO),于2019年1月18日至2022年10月17日期间进行。对心脏骤停后处于昏迷状态的18岁或以上的成年患者进行了资格评估;患者来自荷兰的3个重症监护病房。48小时内的预期死亡或12小时内开始治疗的不可行性是排除标准。
■患者随机接受静脉注射酰基生长素释放肽,600μg(干预组),或安慰剂(对照组)在心脏骤停后12小时内,持续7天,每天两次,除了标准护理。
■主要结果是6个月时的脑功能类别(CPC)量表评分。安全性结果包括任何严重不良事件。次要结果是第1天和第3天的死亡率和神经元特异性烯醇化酶(NSE)水平。
■总共对783名心脏骤停后昏迷的成年患者进行了资格评估,和160名患者(中位[IQR]年龄,68[57-75]岁;120名男性[75%])入组。共有81名患者(51%)被分配到干预组,79人(49%)被分配到对照组.干预组CPC改善的共同比值比(OR)为1.78(95%CI,0.98-3.22;P=.06)。这在所有CPC类别上都是一致的。心脏骤停后第1天的平均(SD)NSE水平在干预组(34[6]μg/L比56[13]μg/L;P=.04)和第3天(28[6]μg/L比52[14]μg/L;P=.08)显著降低。两组之间严重不良事件的发生率和类型相当。干预组的死亡率为37%(81个中的30个),对照组为51%(79个中的40个)(绝对风险降低,14%;95%CI,-2%至29%;P=.08)。
■心脏骤停后昏迷的患者,酰基-ghrelin静脉治疗是安全的,并有可能有效改善神经系统预后.需要进行3期试验才能获得确凿的证据。
■临床试验登记簿。欧盟:EUCTR2018-000005-23-NL。
UNASSIGNED: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-
ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human
study populations.
UNASSIGNED: To determine safety and potential efficacy of intravenous acyl-
ghrelin to improve neurological outcome in patients in a coma after cardiac arrest.
UNASSIGNED: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical
trial,
Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical
Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria.
UNASSIGNED: Patients were randomized to receive intravenous acyl-ghrelin, 600 μg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care.
UNASSIGNED: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3.
UNASSIGNED: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] μg/L vs 56 [13] μg/L; P = .04) and on day 3 (28 [6] μg/L vs 52 [14] μg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08).
UNASSIGNED: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence.
UNASSIGNED: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.