Clinical trial NCT02757443: Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients
Official title: Myocardial Protection With Phosphocreatine in High-RIsk Cardiac SurgEry Patients: a Single-center Randomised Double-blind Placebo-controlled Exploratory Pilot Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiac Surgical Procedures
Heart Valve Prosthesis Implantation
Keywords: Phosphocreatine
Creatine Phosphate
Neoton
Phosphate, Creatine
Phosphorylcreatine
Lead sponsor: Meshalkin Research Institute of Pathology of Circulation
Sponsor class: NETWORK
First posted: 2016-05-02
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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
* 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.

Primary outcomes:
measure: Peak concentration of Troponin I
timeFrame: From the randomization to the postoperative day 3 (POD 3)
Secondary outcomes:
measure: The need for (yes/no), and dosage (inotropic score) of, inotropic agents
timeFrame: through study completion, an average of 4 weeks
measure: The need for (yes/no), the number of and the dosage of, defibrillation
timeFrame: through study completion, an average of 4 weeks
measure: The incidence of new-onset moderate and severe arrhythmias or cardiac arrest
timeFrame: through study completion, an average of 4 weeks
measure: Cardiac index
timeFrame: at 6 h after ICU admission, and at the beginning of POD 1
measure: Left ventricular ejection fraction
timeFrame: At the beginning of POD 1
measure: Peak serum creatinine concentration
timeFrame: through study completion, an average of 4 weeks
measure: The incidence of acute kidney injury
timeFrame: through study completion, an average of 4 weeks
measure: Sequential Organ Failure Assessment score
timeFrame: through study completion, an average of 4 weeks
measure: Duration of mechanical ventilation
timeFrame: through study completion, an average of 4 weeks
measure: Duration of ICU stay
timeFrame: through study completion, an average of 4 weeks
measure: Duration of hospital stay
timeFrame: through study completion, an average of 4 weeks
measure: 30-day all-cause mortality
timeFrame: 30 days after randomisation
Other outcomes:
Locations:
city: Novosibirsk
country: Russian Federation
facility: Evgeny Fominskiy
Study officials:
affiliation: Academician EN Meshalkin Novosibirsk Research Institute of Circulation Pathology
name: Evgeny V. Fominskiy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.