Remote Ischemic Conditioning to Attenuate Myocardial Death and Improve Operative Outcome.

Phase 2

• Conditions: Coronary Artery Bypass; Myocardial Reperfusion Injur; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial
• Interventions: Procedure: Remote Ischemic Preconditioning with Postconditioning; Procedure: Sham RIPC procedure

• Registration Number: NCT03363958
• Lead Sponsor: Medinet Heart Centre

Brief Summary

This study evaluates the addition of remote ischemic preconditioning and postconditioning to standard myocardial protection protocol in patients submitted to off - pump coronary artery bypass grafting in a prospective, 1:1 randomized, double blind fashion. An interventional group will receive remote ischemic preconditioning 24-hours before OP-CABG, immediately before surgery and within 60 minutes following surgery by means of lower limb ischemia achieved by pressure cuff inflation, whereas control group will receive sham procedure perioperatively.

Detailed Description

In a prospective, 1:1 randomized and double blind fashion, the study will evaluate the impact of remote ischemic preconditioning, both immediate and second window of protection (24 hours and immediately before surgery) with remote ischemic postconditiong on operative outcomes in patients submitted to coronary artery bypass grafting without use of extracorporeal circulation.

Remote ischemic conditioning was found to provide protection against necrosis and apoptosis due to ischemia and reperfusion injury, a phenomenon observed during coronary artery bypass grafting. That in turn was associated with poor postoperative outcomes, predominantly poor survival.

Remote ischemic preconditioning will be provided by repeated lower leg ischemia and reperfusion with pressure cuff inflation for five minutes and deflation for five minutes in three consecutive cycles. Remote ischemic preconditioning will be performed 24 hours before CABG and immediately before surgery. Remote ischemic postconditioning will be performed within 60 minutes following the last coronary artery bypass graft completion and the restoration of coronary blood flow.

The study will assess clinical endpoints such as postoperative acute myocardial infarction (type 5 MI), postoperative mortality, postoperative renal failure and laboratory outcomes such as postoperative serial measurements of troponin T release or glomerular filtration rate as secondary outcomes.

Study Timeline

• Study Start: 2014-01-01
• Status Verified: 2017-11
• Study First Submitted: 2017-11-30
• Study First Submitted QC: 2017-11-30
• Last Update Submitted: 2017-11-30
• Study First Posted: 2017-12-06
• Last Update Posted: 2017-12-06
• Primary Completion: 2019-01-01
• Study Completion: 2020-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Patients qualified to coronary artery bypass grafting according to ESC/EACTS Guidelines of myocardial revascularization, suffering from:

• Multivessel coronary artery disease amenable for surgical treatment
• Negative history of previous cardiac or vascular surgery in childhood and afterwards.
• Negative history of active neoplastic disease, neither past medical history of oncological treatment
• Patients with non insulin dependent diabetes mellitus treated chronically with oral derivatives of sulfonylourea such as but not limited to: glibenclamide.

Exclusion Criteria

Patients suffering from acute insuficiency of any organ/ system and those suffering from end stage organ failure such as:

• Chronic renal disease - KDOQI stage ≥ 3;
• Chronic renal failure class A by Child - Pugh'a;
• Chronic respiratory failure (type I and II according to Campbell et al. and type I according to Wood et al.);
• Chronic intermittent claudication class 2A according to Fontaine;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RIC Group	Remote Ischemic Preconditioning with Postconditioning	Three cycles of remote ischemic conditioning (5minutes ischemia and 5minutes reperfusion; lower leg ischemia achieved by pressure cuff inflation and deflation); First three cycles the patient will receive 24 hours preoperatively, second three cycles the patient will receive after the induction of general anesthesia but before skin incision shortly before CABG. Remote ischemic postconditioning (5minutes ischemia and 5minutes reperfusion; lower leg ischemia achieved by pressure cuff inflation and deflation) will be administered to the patient within 60 minutes after the completion of all coronary artery bypass grafts and the restoration of coronary blood flow.
Control Group	Sham RIPC procedure	Control group will receive sham procedure near identical to intervention. That will be afforded by inflation of pressure cuff on artificial leg hidden under the draping by an assistant who is not included in the research team and does not have any connection to study design and data analysis.

Primary Outcome Measures

Name	Time	Method
Postoperative myocardial necrosis	72 hours postoperatively	Serial mesurements of High - Sensitive Troponin T release
Postoperative kidney injury	7 days postoperatively	Serial measurements of estimated glomerular filtration rate by creatinine

Secondary Outcome Measures

Name	Time	Method
Postoperative Acute Kidney Injury	30 days	Prevalence of acute kidney injury according to Society of Thoracic Surgeons definitions of outcomes.
Perioperative mortality	30 days postoperatively	30-day all cause mortality
Perioperative myocardial infarction	30 days postoperatively	30-day myocardial infarction

Trial Locations

Locations (1)

Medinet Heart Centre; 🇵🇱 Nowa Sol, Lubuskie, Poland