Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in CABG Surgery

Study Overview
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Brief Summary
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Coronary heart disease (CHD) is the leading cause of death in the UK, accounting for 124,000 deaths (2006) and costing the UK economy over £7.9 billion a year. Patients with severe CHD are usually treated by coronary artery bypass graft (CABG) surgery, the risks of which are increasing due to older and sicker patients being operated on. New treatment strategies are therefore required to improve health outcomes in these high-risk patients undergoing CABG with or without valve (CABG±valve) surgery. The hypothesis tested in this research proposal is that remote ischaemic preconditioning (RIC), a virtually cost-free, non-pharmacological and simple non-invasive strategy for reducing the damage to the heart muscle at the time of surgery, improves health outcomes in high-risk patients undergoing CABG±valve surgery. In this research project, 1610 high-risk patients undergoing CABG±valve surgery will be recruited via 28 UK hospitals performing heart surgery. Patients will be randomly allocated to receive either RIC or control. For RIC, a blood pressure cuff will be placed on the upper arm to temporarily deprive it of oxygen and nutrients, an intervention which has been shown in the investigators pilot studies to reduce damage to the heart muscle by up to 40% during CABG±valve surgery. The investigators will determine whether RIC can improve health outcomes in terms of better patient survival, less heart attacks and strokes, shorter hospital stay; less damage to the heart, kidney and brain during surgery; better heart function post-surgery and less chance of developing heart failure; better exercise tolerance and quality of life.

Official Title
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Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in Coronary Artery Bypass Graft Surgery

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Procedure: Remote ischaemic preconditioning
* Procedure: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing CABG with or without valve surgery using blood cardioplegia Patients aged 18 years and above Patients with an additive Euroscore greater than or equal to 5 Exclusion Criteria: Cardiogenic shock Cardiac arrest on current admission Pregnancy Significant peripheral arterial disease affecting the upper limbs Patients with significant hepatic dysfunction (Prothrombin>2.0 ratio) Patients with significant pulmonary disease (FEV1<40% predicted) Patients with known renal failure with a GFR<30 mL/min/1.73 m2 Patients on glibenclamide or nicorandil, as these medications may interfere with RIC Patients recruited into another study which may impact on the ERICCA study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Control treatment (sham RIC) will consist of four 5-minute simulated inflations of a blood pressure cuff placed on the upper arm. The inflations will be separated by 5-minute periods when the blood pressure cuff will be deflated. | Procedure: Control<br>* Control treatment (sham RIC) will consist of four 5-minute simulated inflations of a blood pressure cuff placed on the upper arm. The inflations will be separated by 5-minute periods when the blood pressure cuff will be deflated.<br>|
| Active Comparator: Remote ischaemic conditioning<br>Blood pressure cuff placed on upper arm and inflated to 200mmHg for 5 minutes then deflated for 5 minutes - this cycle is repeated a total of 4 times. | Procedure: Remote ischaemic preconditioning<br>* Blood pressure cuff placed on upper arm and inflated to 200mmHg for 5 minutes then deflated for 5 minutes - this cycle is repeated a total of 4 times.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac and cerebral events | Combined endpoint of Cardiovascular death, MI, Revascularisation and Stroke. | One year post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-operative myocardial injury | 72 hours area under curve serum troponin-T | 72 hours peri-operative period | 
| LV ejection fraction | Echo determined LV ejection fraction | At one year | 
| Acute kidney injury | Acute kidney injury score and 24 hour area under curve serum NGAL | Peri-operative | 
| 30 day MACCE | Major adverse cardiac and cerebral events 30 days post surgery | 30 days post surgery | 
| All cause death |  | 1 year post surgery | 
| Length of ITU stay |  | ITU stay | 
| Length of hospital stay |  | Until hospital discharge | 
| Inotrope score | Inotrope score after 72 hours | 72 hours post surgery | 
| 6 minute Walk Test |  | 6 weeks and 12 months post surgery | 
| Quality of Life | Quality of Life assessed using the EQ-5D measurement | 6 weeks, 3/6/9 and 12 months post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischemic preconditioning, Coronary artery bypass graft surgery, Cardioprotection, Clinical Outcomes