Lund University, Skåne University Hospital, Department of Clinical Sciences, Cardiology, Lund, Sweden.
Lund University, Skåne University Hospital, Department of Clinical Sciences, Neurology, Lund, Sweden.
Am Heart J. 2019 Nov;217:23-31. doi: 10.1016/j.ahj.2019.06.012. Epub 2019 Jun 26.
Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted.
The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4-6) at 180 days after arrest.
The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest.
比较低温治疗与常规治疗在院外心脏骤停患者中的效果的随机试验中，纳入的患者不足 500 人，且这些试验大多规模较小，存在较高的偏倚风险。因此，关于这种潜在有益干预措施的数据积累类似于小型 II 期试验后药物的情况。因此，需要进行一项大型的确认性试验。
TTM2 试验是一项国际、多中心、平行组、研究者发起的、随机、优效性试验，该试验将比较心脏骤停后目标温度为 33°C 与维持正常体温和早期治疗发热（≥37.8°C）的策略。在自主循环恢复后 3 小时内，患者将被随机分组，两组的干预期均为 40 小时。所有患者在整个干预期间都必须进行镇静。由于难以对干预措施进行盲法，直接参与患者护理的临床团队将无法对分组情况进行盲法。预后评估者、结局评估者、指导小组、试验协调团队和试验统计学家将进行盲法。主要结局是随机分组后 180 天的全因死亡率。我们估计对照组的死亡率为 55%。为了以 0.05 的显著性水平和 90%的把握度检测到绝对风险降低 7.5%，需要纳入 1900 名参与者。主要的次要神经学结局是 180 天后不良的功能结局（改良 Rankin 量表 4-6）。
TTM2 试验将比较院外心脏骤停后低温治疗与 33°C 低温治疗与常规治疗和早期治疗发热（≥37.8°C）的效果。
