Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients

NCT02757443 | Completed Phase 3 DMC

• 1 other identifier: PCr-in-CS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiac Surgical Procedures; Heart Valve Prosthesis Implantation

Keywords

Phosphocreatine; Creatine Phosphate; Neoton; Phosphate, Creatine; Phosphorylcreatine

Outcome Measures

Primary Outcomes (1)

• Peak concentration of Troponin I

  From the randomization to the postoperative day 3 (POD 3)

Secondary Outcomes (12)

• 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

Study Arms (2)

Phosphocreatine

EXPERIMENTAL

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; Drug: Phosphocreatine sodium tetrahydrate added to cardioplegia; Drug: Phosphocreatine sodium tetrahydrate after heart recovery; Drug: Phosphocreatine sodium tetrahydrate after ICU admission

Control

PLACEBO COMPARATOR

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; Drug: 5% Glucose; Drug: 5% Glucose after heart recovery; Drug: 5% Glucose after ICU admission

Interventions

Phosphocreatine sodium tetrahydrate after anaesthesia induction DRUG

after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV)

Also known as: Neoton

Phosphocreatine

5% Glucose after anaesthesia induction DRUG

after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes

Also known as: Dextrose

Control

Phosphocreatine sodium tetrahydrate added to cardioplegia DRUG

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)

Also known as: Neoton

Phosphocreatine

5% Glucose DRUG

together with cardioplegia 50 mL of glucose 5% is added in every 1 L of cardioplegic solution (Custodiol, Dr. F. KOHLER CHEMIE, GmbH, Germany)

Also known as: Dextrose added to cardioplegia

Control

Phosphocreatine sodium tetrahydrate after heart recovery DRUG

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

Also known as: Neoton

Phosphocreatine

5% Glucose after heart recovery DRUG

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

Also known as: Dextrose

Control

Phosphocreatine sodium tetrahydrate after ICU admission DRUG

immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV

Also known as: Neoton

Phosphocreatine

5% Glucose after ICU admission DRUG

immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes

Also known as: Dextrose

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meshalkin Research Institute of Pathology of Circulation: lead

Study Sites (1)

Evgeny Fominskiy

Novosibirsk, 630055, Russia

Location

Related Publications (4)

• 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;2011(11):CD005184. doi: 10.1002/14651858.CD005184.pub2.

  PMID: 22071819 BACKGROUND

• 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.

  PMID: 22297802 BACKGROUND

• 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.

  PMID: 27318357 BACKGROUND

• Lomivorotov V, Merekin D, Fominskiy E, Ponomarev D, Bogachev-Prokophiev A, Zalesov A, Cherniavsky A, Shilova A, Guvakov D, Lomivorotova L, Lembo R, Landoni G. Myocardial protection with phosphocreatine in high-risk cardiac surgery patients: a randomized trial. BMC Anesthesiol. 2023 Nov 29;23(1):389. doi: 10.1186/s12871-023-02341-4.

  PMID: 38030971 DERIVED

MeSH Terms

Interventions

Phosphocreatine; Glucose

Intervention Hierarchy (Ancestors)

Creatine; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoamino Acids; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Evgeny V. Fominskiy, MD PhD

  Academician EN Meshalkin Novosibirsk Research Institute of Circulation Pathology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: May 2, 2016
• Study Start: June 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: May 1, 2021
• Last Updated: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

RU (1)