Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients

Phase 3

Completed

• Conditions: Cardiac Surgical Procedures; Heart Valve Prosthesis Implantation
• Interventions: Drug: 5% Glucose after anaesthesia induction; Drug: Phosphocreatine sodium tetrahydrate after anaesthesia induction; Drug: Phosphocreatine sodium tetrahydrate added to cardioplegia; Drug: 5% Glucose; Drug: Phosphocreatine sodium tetrahydrate after heart recovery; Drug: 5% Glucose after heart recovery; Drug: Phosphocreatine sodium tetrahydrate after ICU admission; Drug: 5% Glucose after ICU admission

• Registration Number: NCT02757443
• Lead Sponsor: Meshalkin Research Institute of Pathology of Circulation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-13
• Study First Submitted QC: 2016-04-27
• Study First Posted: 2016-05-02
• Study Start: 2016-06
• Primary Completion: 2021-04
• Study Completion: 2021-05
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-28
• Last Update Posted: 2021-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Double/triple valve lesion that required cardiac surgery with CPB
• Aged 18 years or older
• Signed informed consent

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	5% Glucose after anaesthesia induction	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
Phosphocreatine	Phosphocreatine sodium tetrahydrate after anaesthesia induction	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
Phosphocreatine	Phosphocreatine sodium tetrahydrate added to cardioplegia	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
Phosphocreatine	Phosphocreatine sodium tetrahydrate after heart recovery	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
Phosphocreatine	Phosphocreatine sodium tetrahydrate after ICU admission	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
Control	5% Glucose	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
Control	5% Glucose after heart recovery	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
Control	5% Glucose after ICU admission	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

Primary Outcome Measures

Name	Time	Method
Peak concentration of Troponin I	From the randomization to the postoperative day 3 (POD 3)

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Evgeny Fominskiy; 🇷🇺 Novosibirsk, Russian Federation