Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
BMJ Open. 2021 Nov 5;11(11):e052340. doi: 10.1136/bmjopen-2021-052340.
Coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) are associated with risk of death, as well as brain, heart and kidney injury. Glucagon-like peptide-1 (GLP-1) analogues are approved for treatment of type 2 diabetes, and GLP-1 analogues have been suggested to have potential organ-protective and anti-inflammatory effects. During cardiopulmonary bypass (CPB), consensus on the optimal fraction of oxygen is lacking. The objective of this study is to determine the efficacy of the GLP-1-analogue exenatide versus placebo and restrictive oxygenation (50% fractional inspired oxygen, FiO2) versus liberal oxygenation (100% FiO2) in patients undergoing open heart surgery.
A randomised, placebo-controlled, double blind (for the exenatide intervention)/single blind (for the oxygenation strategy), 2×2 factorial designed single-centre trial on adult patients undergoing elective or subacute CABG and/or surgical AVR. Patients will be randomised in a 1:1 and 1:1 ratio to a 6-hour and 15 min infusion of 17.4 µg of exenatide or placebo during CPB and to a FiO2 of 50% or 100% during and after weaning from CPB. Patients will be followed until 12 months after inclusion of the last participant. The primary composite endpoint consists of time to first event of death, renal failure requiring renal replacement therapy, hospitalisation for stroke or heart failure. In addition, the trial will include predefined sub-studies applying more advanced measures of cardiac- and pulmonary dysfunction, renal dysfunction and cerebral dysfunction. The trial is event driven and aims at 323 primary endpoints with a projected inclusion of 1400 patients.
Eligible patients will provide informed, written consent prior to randomisation. The trial is approved by the local ethics committee and is conducted in accordance with Danish legislation and the Declaration of Helsinki. The results will be presented in peer-reviewed journals.
NCT02673931.
冠状动脉旁路移植术（CABG）和/或主动脉瓣置换术（AVR）与死亡风险以及脑、心和肾损伤有关。胰高血糖素样肽-1（GLP-1）类似物已被批准用于治疗 2 型糖尿病，并且 GLP-1 类似物具有潜在的器官保护和抗炎作用。在体外循环（CPB）期间，关于最佳氧分数的共识尚未达成。本研究的目的是确定 GLP-1 类似物 exenatide 与安慰剂以及限制氧合（50%吸入氧分数，FiO2）与自由氧合（100% FiO2）在接受心脏直视手术的患者中的疗效。
一项随机、安慰剂对照、双盲（针对 exenatide 干预）/单盲（针对氧合策略）、2×2 析因设计的单中心试验，纳入接受择期或亚急性 CABG 和/或外科 AVR 的成年患者。患者将以 1:1 和 1:1 的比例随机分配至 CPB 期间 6 小时 15 分钟输注 17.4µg exenatide 或安慰剂，以及 CPB 脱机期间和之后 FiO2 为 50%或 100%。患者将随访至最后一名参与者纳入后 12 个月。主要复合终点包括首次死亡、需要肾脏替代治疗的肾衰竭、因中风或心力衰竭住院的时间。此外，该试验将包括应用更先进的心脏和肺功能、肾功能和脑功能障碍测量的预设子研究。该试验是事件驱动的，目标是 323 个主要终点，预计纳入 1400 名患者。
符合条件的患者将在随机分组前提供知情、书面同意。该试验已获得当地伦理委员会的批准，并符合丹麦法规和《赫尔辛基宣言》。结果将在同行评议的期刊上发表。
NCT02673931。
