Preconditioning Shields Against Vascular Events in Surgery

NCT01691911 | Completed DMC

• 1 other identifier: SAVES-123
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Major vascular surgery involves operations to repair swollen blood vessels, clear debris from blocked arteries or bypass blocked blood vessels. Patients with these problems are a high-risk surgical group as they have generalized blood vessel disease. These puts them at risk of major complications around the time of surgery such as heart attacks , strokes and death. The mortality following repair of a swollen main artery in the abdomen is about 1 in 20. This contrasts poorly with the 1 per 100 risk of death following a heart bypass. Simple and cost-effective methods are needed to reduce the risks of major vascular surgery. Remote ischaemic preconditioning (RIPC) may be such a technique. To induce RIPC, the blood supply to muscle in the patient's arm is interrupted for about 5 minutes. It is then restored for a further five minutes. This cycle is repeated three more times. The blood supply is interrupted simply by inflating a blood pressure cuff to maximum pressure. This repeated brief interruption of the muscular blood supply sends signals to critical organs such as the brain and heart, which are rendered temporarily resistant to damage from reduced blood supply. Several small randomized clinical trials in patients undergoing different types of major vascular surgery have demonstrated a potential benefit. This large, multi-centre trial aims to determine whether RIPC can reduce complications in routine practice.

Conditions

Abdominal Aortic Aneurysm; Carotid Atherosclerosis; Critical Lower Limb Ischaemia

Keywords

Vascular disease; Open aortic aneurysm repair; Endovascular aneurysm repair; Carotid endartrectomy; Lower limb surgical revascularisation; Major lower limb amputation

Outcome Measures

Primary Outcomes (1)

• Major Adverse Clinical Events

  The primary endpoint for the trial will be Major Adverse Clinical Events. This is a composite endpoint comprising any of: cardiovascular death, myocardial infarction, new onset arrhythmia requiring treatment, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischaemia requiring intervention or biopsy proven ischaemic colitis, urgent cardiac revascularisation. All participants will undergo a serum troponin levels and 12-lead electrocardiogram on the second post-operative day to screen for silent peri-operative myocardial infarction. Trial ECGs and troponin levels will be interpreted by a blinded trial cardiologist.

  30 day

Secondary Outcomes (5)

• Duration of post-operative hospital stay

  30 day

• Duration of intensive care unit stay

  30 day

• Unplanned critical care unit admission

  30 day

• Acute kidney injury score in first three peri-operative days

  3 days

• Peri-operative myocardial injury

  from operation to 72 hours postoperatively

Study Arms (2)

Remote preconditioning

EXPERIMENTAL

Preconditioning will be performed in the same manner as several previous trials. Immediately after induction of anaesthesia, a standard, CE-approved blood pressure cuff will be placed around one arm of the patient. It will then be inflated to a pressure of 200mmHg for 5 minutes. For patients with a systolic blood pressure \>185mmHg, the cuff will be inflated to at least 15mmHg above the patient's systolic blood pressure. The cuff will then be deflated and the arm allowed reperfuse for 5 minutes. This will be repeated so that each patient receives a total of 4 ischaemia-reperfusion cycles. In all other respects, the procedure and peri-operative care will follow the routine practices of the surgeons and anaesthetists involved.

Procedure: Remote preconditioning

Remote preconditioning control

NO INTERVENTION

Patients randomised to this group will receive routine pre-operative, peri-operative and post operative care.

Interventions

Remote preconditioning PROCEDURE

Immediately after induction of anaesthesia, a standard, CE-approved tourniquet cuff will be placed around one arm of the patient. It will then be inflated to a pressure of 200mmHg for 5 minutes. For patients with a systolic blood pressure \>185mmHg, the cuff will be inflated to at least 15mmHg above the patient's systolic blood pressure. The cuff will then be deflated and the arm allowed reperfuse for 5 minutes. This will be repeated so that each patient receives a total of 4 ischaemia-reperfusion cycles. In all other respects, the procedure and peri-operative care will follow the routine practices of the surgeons and anaesthetists involved.

Remote preconditioning

Eligibility Criteria

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

You may qualify if:

• Age greater than 18 years
• patient willing to give full informed consent for participation
• Patients undergoing elective carotid endarterectomy or
• Patients undergoing open abdominal aortic aneurysm repair or
• Patients undergoing endovascular abdominal aneurysm repair or
• Patients undergoing surgical lower limb revascularisation (suprainguinal or infrainguinal)

You may not qualify if:

• Patients less than 18 years of age
• Patients who are unable or unwilling to give full informed consent
• Pregnancy
• Significant upper limb peripheral arterial disease
• Patients on glibenclamide or nicorandil (these medications may interfere with remote ischaemic preconditioning)
• Patients with an estimated pre-operative glomerular filtration rate \< 30mls/min/1.73m2
• Patients with a history of myocarditis, pericarditis or amyloidosis
• Patients undergoing Fenestrated or branched EVAR.

Sponsors & Collaborators

• Mid Western Regional Hospital, Ireland: lead

Study Sites (1)

MidWestern Regional Hospital

Limerick, Limerick, 000, Ireland

Location

Related Publications (12)

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  PMID: 15192558 BACKGROUND

• Chambers BR, Donnan GA. Carotid endarterectomy for asymptomatic carotid stenosis. Cochrane Database Syst Rev. 2005 Oct 19;2005(4):CD001923. doi: 10.1002/14651858.CD001923.pub2.

  PMID: 16235289 BACKGROUND

• Greenhalgh RM, Brown LC, Kwong GP, Powell JT, Thompson SG; EVAR trial participants. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet. 2004 Sep 4-10;364(9437):843-8. doi: 10.1016/S0140-6736(04)16979-1.

  PMID: 15351191 BACKGROUND

• Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124-36. doi: 10.1161/01.cir.74.5.1124.

  PMID: 3769170 BACKGROUND

• Jenkins DP, Pugsley WB, Alkhulaifi AM, Kemp M, Hooper J, Yellon DM. Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. Heart. 1997 Apr;77(4):314-8. doi: 10.1136/hrt.77.4.314.

  PMID: 9155608 BACKGROUND

• Clavien PA, Selzner M, Rudiger HA, Graf R, Kadry Z, Rousson V, Jochum W. A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003 Dec;238(6):843-50; discussion 851-2. doi: 10.1097/01.sla.0000098620.27623.7d.

  PMID: 14631221 BACKGROUND

• Walsh SR, Tang TY, Kullar P, Jenkins DP, Dutka DP, Gaunt ME. Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur J Cardiothorac Surg. 2008 Nov;34(5):985-94. doi: 10.1016/j.ejcts.2008.07.062. Epub 2008 Sep 9.

  PMID: 18783958 BACKGROUND

• Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993 Mar;87(3):893-9. doi: 10.1161/01.cir.87.3.893.

  PMID: 7680290 BACKGROUND

• Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation. 1997 Sep 2;96(5):1641-6. doi: 10.1161/01.cir.96.5.1641.

  PMID: 9315559 BACKGROUND

• Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002 Dec 3;106(23):2881-3. doi: 10.1161/01.cir.0000043806.51912.9b.

  PMID: 12460865 BACKGROUND

• Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B. Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol. 1997 Oct;273(4):H1707-12. doi: 10.1152/ajpheart.1997.273.4.H1707.

  PMID: 9362234 BACKGROUND

• Liang F, Liu S, Liu G, Liu H, Wang Q, Song B, Yao L. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD008472. doi: 10.1002/14651858.CD008472.pub3.

  PMID: 36645250 DERIVED

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal; Carotid Artery Diseases; Vascular Diseases

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Cardiovascular Diseases; Aortic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Stewart R Walsh, MCh FRCS

  Mid Western Regional Hospital and University of Limerick

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Stewart Walsh

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 25, 2012
• Study Start: February 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

IE (1)