Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients

Cardiac Surgical Procedures Clinical Trial

— PRISE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02757443
• Other study ID #: PCr-in-CS
• Status: Completed
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: May 2021

Study information

• Verified date: June 2021
• Source: Meshalkin Research Institute of Pathology of Circulation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Surgical Procedures
• Heart Valve Prosthesis Implantation

Intervention

Drug:
• Phosphocreatine sodium tetrahydrate after anaesthesia induction
after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV)
• 5% Glucose after anaesthesia induction
after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes
• Phosphocreatine sodium tetrahydrate added to cardioplegia
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)
• 5% Glucose
together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany)
• Phosphocreatine sodium tetrahydrate after heart recovery
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
• 5% Glucose after heart recovery
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
• Phosphocreatine sodium tetrahydrate after ICU admission
immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
• 5% Glucose after ICU admission
immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes

Locations

Country	Name	City	State
Russian Federation	Evgeny Fominskiy	Novosibirsk

Sponsors (1)

Lead Sponsor	Collaborator
Meshalkin Research Institute of Pathology of Circulation

Country where clinical trial is conducted

Russian Federation, 

References & Publications (3)

Horjus DL, Oudman I, van Montfrans GA, Brewster LM. Creatine and creatine analogues in hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD005184. doi: 10.1002/14651858.CD005184.pub2. Review. — View Citation

Landoni G, Zangrillo A, Lomivorotov VV, Likhvantsev V, Ma J, De Simone F, Fominskiy E. Cardiac protection with phosphocreatine: a meta-analysis. Interact Cardiovasc Thorac Surg. 2016 Oct;23(4):637-46. doi: 10.1093/icvts/ivw171. Epub 2016 Jun 17. Review. — View Citation

Strumia E, Pelliccia F, D'Ambrosio G. Creatine phosphate: pharmacological and clinical perspectives. Adv Ther. 2012 Feb;29(2):99-123. doi: 10.1007/s12325-011-0091-4. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak concentration of Troponin I		From the randomization to the postoperative day 3 (POD 3)
Secondary	The need for (yes/no), and dosage (inotropic score) of, inotropic agents		through study completion, an average of 4 weeks
Secondary	The need for (yes/no), the number of and the dosage of, defibrillation		through study completion, an average of 4 weeks
Secondary	The incidence of new-onset moderate and severe arrhythmias or cardiac arrest		through study completion, an average of 4 weeks
Secondary	Cardiac index		at 6 h after ICU admission, and at the beginning of POD 1
Secondary	Left ventricular ejection fraction		At the beginning of POD 1
Secondary	Peak serum creatinine concentration		through study completion, an average of 4 weeks
Secondary	The incidence of acute kidney injury		through study completion, an average of 4 weeks
Secondary	Sequential Organ Failure Assessment score		through study completion, an average of 4 weeks
Secondary	Duration of mechanical ventilation		through study completion, an average of 4 weeks
Secondary	Duration of ICU stay		through study completion, an average of 4 weeks
Secondary	Duration of hospital stay		through study completion, an average of 4 weeks
Secondary	30-day all-cause mortality		30 days after randomisation