Clinical trial NCT01247545: Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in CABG Surgery
Official title: Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in Coronary Artery Bypass Graft Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Heart Disease
Keywords: Remote ischemic preconditioning
Coronary artery bypass graft surgery
Cardioprotection
Clinical Outcomes
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2010-11-24
Enrollment: 1612
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients undergoing CABG with or without valve surgery using blood cardioplegia
2. Patients aged 18 years and above
3. Patients with an additive Euroscore greater than or equal to 5

Exclusion Criteria:

1. Cardiogenic shock
2. Cardiac arrest on current admission
3. Pregnancy
4. Significant peripheral arterial disease affecting the upper limbs
5. Patients with significant hepatic dysfunction (Prothrombin\>2.0 ratio)
6. Patients with significant pulmonary disease (FEV1\<40% predicted)
7. Patients with known renal failure with a GFR\<30 mL/min/1.73 m2
8. Patients on glibenclamide or nicorandil, as these medications may interfere with RIC
9. Patients recruited into another study which may impact on the ERICCA study

Primary outcomes:
measure: Major adverse cardiac and cerebral events
timeFrame: One year post-surgery
Secondary outcomes:
measure: Peri-operative myocardial injury
timeFrame: 72 hours peri-operative period
measure: LV ejection fraction
timeFrame: At one year
measure: Acute kidney injury
timeFrame: Peri-operative
measure: 30 day MACCE
timeFrame: 30 days post surgery
measure: All cause death
timeFrame: 1 year post surgery
measure: Length of ITU stay
timeFrame: ITU stay
measure: Length of hospital stay
timeFrame: Until hospital discharge
measure: Inotrope score
timeFrame: 72 hours post surgery
measure: 6 minute Walk Test
timeFrame: 6 weeks and 12 months post surgery
measure: Quality of Life
timeFrame: 6 weeks, 3/6/9 and 12 months post surgery
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Essex Cardiothoracic Centre
state: Essex
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: Sussex
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Cardiff
country: United Kingdom
facility: Cardiff & Vale University Health Board
city: Edinburgh
country: United Kingdom
facility: Edinburgh Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Golden Jubilee Hospital
city: Harefield
country: United Kingdom
facility: Harefield Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Kings College London Hospital
city: London
country: United Kingdom
facility: London Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: St Thomas Hospital
city: London
country: United Kingdom
facility: UCLH Heart Hospital
city: Manchester
country: United Kingdom
facility: John Radcliffe Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Trent Cardiac Centre
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Swansea
country: United Kingdom
facility: Swansea Hospital
city: Wolverhampton
country: United Kingdom
facility: Wolverhampton Hospital
Study officials:
affiliation: University College, London
name: Derek J Hausenloy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007 Aug 18;370(9587):575-9. doi: 10.1016/S0140-6736(07)61296-3.
citation: Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J, Yellon DM. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial. Heart. 2009 Oct;95(19):1567-71. doi: 10.1136/hrt.2008.155770. Epub 2009 Jun 8.
citation: Venugopal V, Laing CM, Ludman A, Yellon DM, Hausenloy D. Effect of remote ischemic preconditioning on acute kidney injury in nondiabetic patients undergoing coronary artery bypass graft surgery: a secondary analysis of 2 small randomized trials. Am J Kidney Dis. 2010 Dec;56(6):1043-9. doi: 10.1053/j.ajkd.2010.07.014. Epub 2010 Oct 25.
citation: Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.
citation: Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM; ERICCA Trial Investigators. Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery. N Engl J Med. 2015 Oct 8;373(15):1408-17. doi: 10.1056/NEJMoa1413534. Epub 2015 Oct 5.
citation: Candilio L, Malik A, Ariti C, Barnard M, Di Salvo C, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, Kolvekar S, Hausenloy DJ, Yellon DM. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart. 2015 Feb;101(3):185-92. doi: 10.1136/heartjnl-2014-306178. Epub 2014 Sep 24.
citation: Hausenloy DJ, Candilio L, Laing C, Kunst G, Pepper J, Kolvekar S, Evans R, Robertson S, Knight R, Ariti C, Clayton T, Yellon DM; ERICCA Trial Investigators. Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial. Clin Res Cardiol. 2012 May;101(5):339-48. doi: 10.1007/s00392-011-0397-x. Epub 2011 Dec 21.