Remote Ischemic Preconditioning of Human Myocardium

NCT01994707 | Completed Phase 2

• 1 other identifier: NCN-2012/07/B/NZ5/02549
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to definitively show if human myocardium can be remotely preconditioned. In the writings there are no experiments that would prove that the remote preconditioning protocol effects on the higher protection of the human myocardial cells, against the ischemia-reperfusion injury. 120 patients referred for coronary artery bypass grafting (CABG) procedure with use of cardiopulmonary bypass are planned will be included to the research. Patients will be randomized (1:1) to one of two groups: remote preconditioning or "placebo" intervention. On the day of surgery, after induction of anesthesia remote preconditioning will be elicited by 3 cycles of 5min inflation (ischemia) and 5 min deflation (reperfusion) of blood pressure cuff on the right arm. In the control group the blood pressure cuff is going to be placed on the upper limb but the preconditioning protocol will not be carried out. On cannulation for CPB, right atrial appendage and myocardial biopsies of the left ventricular will be harvested. The investigators will study: (1) resistance of myocardium to hypoxia/reperfusion injury in in vitro experiments, assessed in isolated right atrial pectinate muscle trabeculae (2) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion in vitro (3) amount of myocardial necrosis in-vivo induced by period of ischemia and reperfusion during CABG as assessed by postoperative myocardial necrosis markers release (4) the systolic function of the myocardium at the postoperative and the kidney function in the postoperative period evaluated by the creatinine clearance; (5) induction of apoptosis and status of mitochondria in myocardium after the period of ischemia, and reperfusion during coronary artery bypass grafting, assessed in myocardial. There is going to be an ability to define does the remote preconditioning influence on the occurrence of apoptosis in the human myocardium in the in vivo conditions and does it influence on the postoperative course in patients undergoing cardiac surgery procedures. The investigators will try to study if remote preconditioning modify induction of apoptosis and its structure in response to injury. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, the future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in controlled experimental setting.

Conditions

Coronary Artery Bypass Graft Triple Vessel; Apoptotic DNA Damage

Keywords

Remote ischemic preconditioning; Coronary artery bypass graft surgery; Troponin T; Apoptosis; Experimental; Cardioprotection

Outcome Measures

Primary Outcomes (1)

• Troponin-T

  Troponin-T release over the perioperative 72-hour period and its area under the curve (AUC)

  72 hours

Secondary Outcomes (5)

• Creatine Kinase isoenzyme MB, full hemodynamic assessment with oxygen metabolic assessment and creatinine clearance (CKD-Epi method)

  1 week post surgery

• Resistance of isolated right atrial pectinate muscle trabeculae to simulated hypoxia/reperfusion in functional organ bath model.

  Day 1 of the RICP intervention

• Resistance of isolated right atrial pectinate muscle trabeculae to induction of apoptosis by simulated hypoxia/reperfusion.

  1day at the moment of harvesting

• Induction of apoptosis and status of mitochondria after the period of ischemia, and reperfusion during coronary artery bypass grafting as assessed in left ventricular myocardial biopsies.

  1 day at the moment of harvesting

• Alveolar-arterial gradient (A-a gradient), S100 concentration, NGAL and zonulin concentration

  1st week post surgery

Study Arms (2)

Remote ischemic preconditioning

ACTIVE COMPARATOR

Left arm blood pressure cuff inflation for 5 min then deflation of cuff for 5 min- cycle repeated 3 times before coronary artery bypass grafting.

Procedure: Remote ischemic preconditioning

Placebo

PLACEBO COMPARATOR

Deflated cuff on arm for 30 minutes.

Procedure: Placebo

Interventions

Remote ischemic preconditioning PROCEDURE

Blood pressure cuff inflation

Remote ischemic preconditioning

Placebo PROCEDURE

Deflated cuff on arm for 30 minutes.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both genders.
• Patients with stable coronary artery disease referred for surgical revascularization in who at least 3 coronary artery bypass grafts are planned with use of cardiopulmonary bypass.

You may not qualify if:

• Age below 18 and above 80.
• Plan to use radial artery as a graft.
• Plan to perform other concomitant cardiac procedure in addition to CABG.
• Diabetes mellitus.
• Troponin T level before surgery in excess of 99th percentile of upper reference limit.
• Acute coronary syndrome in last 14 days before surgery.
• Angina pectoris in last 48 hours before surgery.
• Significant peripheral vascular disease.
• Renal disease with either creatinine level ≥ 2mg/dl or estimated glomerular filtration rate \< 30ml/h/1.73m2.
• Renal replacement therapy.
• Clinically relevant hepatic insufficiency with bilirubin level at least 1.5 times above upper limit of normal or AlAT, AST levels at least 2 times above upper limit of normal.
• Advanced lung disease with FEV1 \< 40% of predicted value.
• Severe systolic dysfunction of left ventricle (EF\<35%).
• Pregnancy.
• Psychiatric disease.

Sponsors & Collaborators

• Medical University of Silesia: lead
• National Science Centre, Poland: collaborator

Study Sites (1)

Medical University of Silesia

Katowice, Poland

Location

Related Publications (2)

• Deja MA, Piekarska M, Malinowski M, Wiaderkiewicz R, Czekaj P, Machej L, Weglarzy A, Kowalowka A, Kolodziej T, Czech E, Plewka D, Mizia M, Latusek T, Szurlej B. Can human myocardium be remotely preconditioned? The results of a randomized controlled trial. Eur J Cardiothorac Surg. 2019 Jun 1;55(6):1086-1094. doi: 10.1093/ejcts/ezy441.

  PMID: 30649238 DERIVED

• Deja MA, Wiaderkiewicz R, Czekaj P, Czech E, Malinowski M, Machej L, Weglarzy A, Kowalowka A, Piekarska M, Szurlej B, Latusek T. Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial. Kardiol Pol. 2018;76(1):136-143. doi: 10.5603/KP.a2017.0180. Epub 2017 Oct 5.

  PMID: 28980297 DERIVED

Study Officials

• Marek A. Deja, MD PhD

  Medical University of Silesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: August 1, 2013
• Primary Completion: January 10, 2016
• Study Completion: April 27, 2016
• Last Updated: January 12, 2018

Record last verified: 2018-01

Locations

PL (1)