Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients

Study Overview
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Brief Summary
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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.

Official Title
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Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients: a Single-center Randomised Double-blind Placebo-controlled Exploratory Pilot Clinical Trial

Conditions
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Cardiac Surgical Procedures, Heart Valve Prosthesis Implantation

Intervention / Treatment
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* Drug: Phosphocreatine sodium tetrahydrate after anaesthesia induction
* Drug: 5% Glucose 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phosphocreatine<br>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 | Drug: Phosphocreatine sodium tetrahydrate after anaesthesia induction<br>* after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV)<br>* Other names: Neoton;Drug: Phosphocreatine sodium tetrahydrate added to cardioplegia<br>* 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)<br>* Other names: Neoton;Drug: Phosphocreatine sodium tetrahydrate after heart recovery<br>* 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<br>* Other names: Neoton;Drug: Phosphocreatine sodium tetrahydrate after ICU admission<br>* immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV<br>* Other names: Neoton;|
| Placebo Comparator: Control<br>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 | Drug: 5% Glucose after anaesthesia induction<br>* after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes<br>* Other names: Dextrose;Drug: 5% Glucose<br>* together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany)<br>* Other names: Dextrose added to cardioplegia;Drug: 5% Glucose after heart recovery<br>* 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<br>* Other names: Dextrose;Drug: 5% Glucose after ICU admission<br>* immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes<br>* Other names: Dextrose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration of Troponin I |  | From the randomization to the postoperative day 3 (POD 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The need for (yes/no), and dosage (inotropic score) of, inotropic agents |  | 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 | 
| 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 | 
| 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 | 
| Sequential Organ Failure Assessment score |  | through study completion, an average of 4 weeks | 
| Duration of mechanical ventilation |  | through study completion, an average of 4 weeks | 
| Duration of ICU stay |  | through study completion, an average of 4 weeks | 
| Duration of hospital stay |  | through study completion, an average of 4 weeks | 
| 30-day all-cause mortality |  | 30 days after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phosphocreatine, Creatine Phosphate, Neoton, Phosphate, Creatine, Phosphorylcreatine