Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in CABG Surgery

NCT01247545 | Completed Phase 3 DMC

• 1 other identifier: 10/0303
• Study Type: interventional
• Target: 1,612
• Locations: 1 country
• Sites: 28

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.

Conditions

Coronary Heart Disease

Keywords

Remote ischemic preconditioning; Coronary artery bypass graft surgery; Cardioprotection; Clinical Outcomes

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiac and cerebral events

  Combined endpoint of Cardiovascular death, MI, Revascularisation and Stroke.

  One year post-surgery

Secondary Outcomes (10)

• Peri-operative myocardial injury

  72 hours peri-operative period

• LV ejection fraction

  At one year

• Acute kidney injury

  Peri-operative

• 30 day MACCE

  30 days post surgery

• All cause death

  1 year post surgery

Study Arms (2)

Control

PLACEBO COMPARATOR

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

Remote ischaemic conditioning

ACTIVE COMPARATOR

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

Interventions

Remote ischaemic preconditioning PROCEDURE

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.

Remote ischaemic conditioning

Control PROCEDURE

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.

Control

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead

Study Sites (28)

Essex Cardiothoracic Centre

Basildon, Essex, United Kingdom

Location

Royal Sussex County Hospital

Brighton, Sussex, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, United Kingdom

Location

Papworth Hospital

Cambridge, United Kingdom

Location

Cardiff & Vale University Health Board

Cardiff, United Kingdom

Location

Edinburgh Royal Infirmary

Edinburgh, United Kingdom

Location

Golden Jubilee Hospital

Glasgow, United Kingdom

Location

Harefield Hospital

Harefield, United Kingdom

Location

Castle Hill Hospital

Hull, United Kingdom

Location

Glenfield Hospital

Leicester, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

Kings College London Hospital

London, United Kingdom

Location

London Chest Hospital

London, United Kingdom

Location

Royal Brompton Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

St George's Hospital

London, United Kingdom

Location

St Thomas Hospital

London, United Kingdom

Location

UCLH Heart Hospital

London, United Kingdom

Location

John Radcliffe Hospital

Manchester, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Trent Cardiac Centre

Nottingham, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Northern General Hospital

Sheffield, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Swansea Hospital

Swansea, United Kingdom

Location

Wolverhampton Hospital

Wolverhampton, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 17707752 BACKGROUND

• 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.

  PMID: 19508973 BACKGROUND

• 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.

  PMID: 20974511 BACKGROUND

• 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.

  PMID: 18456674 BACKGROUND

• 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.

  PMID: 26436207 DERIVED

• 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.

  PMID: 25252696 DERIVED

• 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.

  PMID: 22186969 DERIVED

MeSH Terms

Conditions

Coronary Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Derek J Hausenloy, MD PhD

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 24, 2010
• Study Start: November 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 29, 2015

Record last verified: 2015-05

Locations

GB (28)