Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients (PRISE)

Meshalkin Research Institute of Pathology of Circulation

Status and phase: Completed; Phase 3

Conditions: Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures

Treatments: Drug: Phosphocreatine sodium tetrahydrate after ICU admission; Drug: Phosphocreatine sodium tetrahydrate after anaesthesia induction; Drug: 5% Glucose after heart recovery; Drug: Phosphocreatine sodium tetrahydrate after heart recovery; Drug: 5% Glucose after ICU admission; Drug: 5% Glucose after anaesthesia induction; Drug: 5% Glucose; Drug: Phosphocreatine sodium tetrahydrate added to cardioplegia

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT02757443

PCr-in-CS

Details and patient eligibility

About

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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Phosphocreatine

Experimental group

Description:

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

Treatment:

Drug: Phosphocreatine sodium tetrahydrate added to cardioplegia

Drug: Phosphocreatine sodium tetrahydrate after heart recovery

Drug: Phosphocreatine sodium tetrahydrate after anaesthesia induction

Drug: Phosphocreatine sodium tetrahydrate after ICU admission

Control

Placebo Comparator group

Description:

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

Treatment:

Drug: 5% Glucose

Drug: 5% Glucose after anaesthesia induction

Drug: 5% Glucose after ICU admission

Drug: 5% Glucose after heart recovery