Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients: a Single-center Randomised Double-blind Placebo-controlled Exploratory Pilot Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Peak concentration of Troponin I
研究概览
简要总结
There is evidence on the role of the phosphotransfer system in the energy metabolism of the heart, with altered energetics playing an important role in the mechanisms of heart failure. Phosphocreatine plays an important part in the energy heart system. The investigators have just performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and matched studies that compared phosphocreatine with placebo or standard treatment in patients with coronary artery disease or chronic heart failure or in those undergoing cardiac surgery. Patients receiving phosphocreatine had lower all-cause mortality as well as improved cardiac outcomes when compared to the control group, however, the quality of the included studies was low. Thus, the investigators plan to conduct an exploratory high quality RCT to investigate whether providing phosphocreatine compared to placebo improves the myocardial protection in high-risk patients scheduled for cardiac surgery and to determine the best research endpoint for future trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Double/triple valve lesion that required cardiac surgery with CPB
- •Aged 18 years or older
- •Signed informed consent
排除标准
- •Emergency surgery
- •Concomitant coronary artery bypass grafting surgery (CABG) or procedure on any part of the aorta
- •Chronic kidney disease of G3-G4-G5 categories according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria (at least one of the following present for > 3 months: glomerular filtration rate ≤ 60 ml/min/1.73 m2, history of kidney transplantation) or solitary kidney (by any reason)
- •Known allergy to PCr
- •Pregnancy
- •Current enrollment into another RCT (in the last 30 days)
- •Previous enrollment and randomisation into the PRISE trial
- •Administration of PCr in the previous 30 day
- •Concomitant radiofrequency/cryo- ablation procedure
- •Structural abnormalities or genetic trait point to kidney disease including glomerulonephritis and gout.
研究组 & 干预措施
Phosphocreatine
Participants randomly assigned to the phosphocreatine arm receive:
- after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV);
- together with cardioplegia 2.5 g of PCr prepared in 50 mL of glucose 5% and added to every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany; concentration = 10 mmol/L);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 2 g of PCr prepared in 50 mL of glucose 5% during 30 min IV;
- immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
干预措施: Phosphocreatine sodium tetrahydrate added to cardioplegia (Drug)
Phosphocreatine
Participants randomly assigned to the phosphocreatine arm receive:
- after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV);
- together with cardioplegia 2.5 g of PCr prepared in 50 mL of glucose 5% and added to every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany; concentration = 10 mmol/L);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 2 g of PCr prepared in 50 mL of glucose 5% during 30 min IV;
- immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
干预措施: Phosphocreatine sodium tetrahydrate after anaesthesia induction (Drug)
Phosphocreatine
Participants randomly assigned to the phosphocreatine arm receive:
- after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV);
- together with cardioplegia 2.5 g of PCr prepared in 50 mL of glucose 5% and added to every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany; concentration = 10 mmol/L);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 2 g of PCr prepared in 50 mL of glucose 5% during 30 min IV;
- immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
干预措施: Phosphocreatine sodium tetrahydrate after heart recovery (Drug)
Phosphocreatine
Participants randomly assigned to the phosphocreatine arm receive:
- after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV);
- together with cardioplegia 2.5 g of PCr prepared in 50 mL of glucose 5% and added to every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany; concentration = 10 mmol/L);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 2 g of PCr prepared in 50 mL of glucose 5% during 30 min IV;
- immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
干预措施: Phosphocreatine sodium tetrahydrate after ICU admission (Drug)
Control
Participants randomly assigned to the placebo arm receive:
- after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes
干预措施: 5% Glucose after anaesthesia induction (Drug)
Control
Participants randomly assigned to the placebo arm receive:
- after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes
干预措施: 5% Glucose (Drug)
Control
Participants randomly assigned to the placebo arm receive:
- after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes
干预措施: 5% Glucose after heart recovery (Drug)
Control
Participants randomly assigned to the placebo arm receive:
- after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany);
- immediately after heart recovery (spontaneous or paced myocardium contraction) after aorta declamping 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes;
- immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes
干预措施: 5% Glucose after ICU admission (Drug)
结局指标
主要结局
Peak concentration of Troponin I
时间窗: From the randomization to the postoperative day 3 (POD 3)
次要结局
- The need for (yes/no), and dosage (inotropic score) of, inotropic agents(through study completion, an average of 4 weeks)
- Left ventricular ejection fraction(At the beginning of POD 1)
- Peak serum creatinine concentration(through study completion, an average of 4 weeks)
- The incidence of acute kidney injury(through study completion, an average of 4 weeks)
- Duration of mechanical ventilation(through study completion, an average of 4 weeks)
- Duration of hospital stay(through study completion, an average of 4 weeks)
- The need for (yes/no), the number of and the dosage of, defibrillation(through study completion, an average of 4 weeks)
- Sequential Organ Failure Assessment score(through study completion, an average of 4 weeks)
- Duration of ICU stay(through study completion, an average of 4 weeks)
- 30-day all-cause mortality(30 days after randomisation)
- The incidence of new-onset moderate and severe arrhythmias or cardiac arrest(through study completion, an average of 4 weeks)
- Cardiac index(at 6 h after ICU admission, and at the beginning of POD 1)
研究者
Vladimir Lomivorotov
MD, PhD
Meshalkin Research Institute of Pathology of Circulation