PRISE: Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phosphocreatine 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
after anaesthesia induction 2 g of Phosphocreatine (PCr) prepared in 50 mL of glucose 5% during 30 min intravenous (IV)
Other Names:
Drug: 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)
Other Names:
Drug: 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
Other Names:
Drug: Phosphocreatine sodium tetrahydrate after ICU admission
immediately after ICU admission 4 g of PCr in 100 mL of glucose 5% during 60 min IV
Other Names:
|
| Placebo Comparator: Control 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
after anaesthesia induction 50 mL of glucose 5% IV delivered by an identical infusion pump during 30 minutes
Other Names:
Drug: 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)
Other Names:
Drug: 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
Other Names:
Drug: 5% Glucose after ICU admission
immediately after ICU admission 100 mL of glucose 5% IV delivered by an identical infusion pump during 60 minutes
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Peak concentration of Troponin I [From the randomization to the postoperative day 3 (POD 3)]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
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
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Pregnancy
-
Current enrollment into another RCT (in the last 30 days)
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Previous enrollment and randomisation into the PRISE trial
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Evgeny Fominskiy | Novosibirsk | Russian Federation | 630055 |
Sponsors and Collaborators
- Meshalkin Research Institute of Pathology of Circulation
Investigators
- Principal Investigator: Evgeny V. Fominskiy, MD PhD, Academician EN Meshalkin Novosibirsk Research Institute of Circulation Pathology
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- PCr-in-CS