Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in CABG Surgery

Coronary Heart Disease Clinical Trial

— ERICCA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01247545
• Other study ID #: 10/0303
• Status: Completed
• Phase: Phase 3
• First received: November 22, 2010
• Last updated: May 28, 2015
• Start date: November 2010
• Est. completion date: March 2015

Study information

• Verified date: May 2015
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1612
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Myocardial Ischemia

Intervention

Procedure:
• Remote ischaemic preconditioning
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.
• Control
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.

Locations

Country	Name	City	State
United Kingdom	Essex Cardiothoracic Centre	Basildon	Essex
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	Royal Sussex County Hospital	Brighton	Sussex
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Cardiff & Vale University Health Board	Cardiff
United Kingdom	Edinburgh Royal Infirmary	Edinburgh
United Kingdom	Golden Jubilee Hospital	Glasgow
United Kingdom	Harefield Hospital	Harefield
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Hammersmith Hospital	London
United Kingdom	Kings College London Hospital	London
United Kingdom	London Chest Hospital	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	St Thomas Hospital	London
United Kingdom	UCLH Heart Hospital	London
United Kingdom	John Radcliffe Hospital	Manchester
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Trent Cardiac Centre	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Northern General Hospital	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Swansea Hospital	Swansea
United Kingdom	Wolverhampton Hospital	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiac and cerebral events	Combined endpoint of Cardiovascular death, MI, Revascularisation and Stroke.	One year post-surgery	Yes
Secondary	Peri-operative myocardial injury	72 hours area under curve serum troponin-T	72 hours peri-operative period	Yes
Secondary	LV ejection fraction	Echo determined LV ejection fraction	At one year	No
Secondary	Acute kidney injury	Acute kidney injury score and 24 hour area under curve serum NGAL	Peri-operative	Yes
Secondary	30 day MACCE	Major adverse cardiac and cerebral events 30 days post surgery	30 days post surgery	Yes
Secondary	All cause death		1 year post surgery	Yes
Secondary	Length of ITU stay		ITU stay	No
Secondary	Length of hospital stay		Until hospital discharge	No
Secondary	Inotrope score	Inotrope score after 72 hours	72 hours post surgery	No
Secondary	6 minute Walk Test		6 weeks and 12 months post surgery	No
Secondary	Quality of Life	Quality of Life assessed using the EQ-5D measurement	6 weeks, 3/6/9 and 12 months post surgery	No