Preconditioning Shields Against Vascular Events in Surgery

NCT02097186 | Unknown DMC

• 1 other identifier: SAVES-F
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 6

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)

• Serum troponin levels

  The trial is intended to pragmatically evaluate the potential of RIPC to improve clinical outcomes among patients undergoing major vascular surgery in routine clinical practice. For the pilot trial, a surrogate marker of efficacy will be used, namely serum troponin I levels. The primary efficacy outcome will be a comparison of the proportion of patients in each arm of the trial who develop a serum troponin level in excess of the upper limit of normal in the first three post-operative days.

  3 days

Secondary Outcomes (11)

• Composite Major Adverse Clinical Events

  30 day

• 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

Other Outcomes (2)

• Acceptability of RIPC to patients

  6 weeks

• Acceptability and barriers to implementation among healthcare professionals.

  24 months

Study Arms (2)

Remote ischaemic preconditioning

EXPERIMENTAL

Remote ischaemic 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 ischaemic preconditioning

Control to remote preconditioning group

NO INTERVENTION

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

Interventions

Remote ischaemic preconditioning PROCEDURE

Ischaemic preconditioning is a phenomenon whereby a brief period of non-lethal ischaemia in a tissue renders it resistant to the effects of a subsequent much longer ischaemic insult. Remote ischaemic preconditioning works on the theory that brief ischaemia in one tissue could confer protection on distant organs.

Also known as: RIPC

Remote ischaemic 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:

• Pregnancy
• Significant upper limb peripheral arterial disease
• Previous history of upper limb deep vein thrombosis
• Patients on glibenclamide or nicorandil (these medications may interfere with RIPC) Patients with an estimated pre-operative glomerular filtration rate \< 30mls/min/1.73m2
• Patients with a known history of myocarditis, pericarditis or amyloidosis
• Patients with an estimated pre-operative glomerular filtration rate \< 30mls/min/1.73m2.
• Patients with severe hepatic disease defined as an international normalised ratio \>2 in the absence of systemic anticoagulation
• Patients with severe respiratory disease (for the trial, defined as patients requiring home oxygen therapy)
• Patients previously enrolled in the trial representing for a further procedure
• Patients with previous axillary surgery

Sponsors & Collaborators

• Mid Western Regional Hospital, Ireland: lead

Study Sites (6)

Cork University Hospital

Cork, Cork, 000, Ireland

NOT YET RECRUITING

Beaumont Hospital

Dublin, Dublin, 000, Ireland

RECRUITING

St James's Hospital

Dublin, Dublin, 000, Ireland

RECRUITING

University Hospital Limerick (AKA MidWestern Regional Hospital)

Limerick, Limerick, 000, Ireland

RECRUITING

Waterford Regional Hospital

Waterford, Waterford, 000, Ireland

RECRUITING

University Hospital Galway

Galway, 00, Ireland

RECRUITING

Related Publications (12)

• Anderson PL, Gelijns A, Moskowitz A, Arons R, Gupta L, Weinberg A, Faries PL, Nowygrod R, Kent KC. Understanding trends in inpatient surgical volume: vascular interventions, 1980-2000. J Vasc Surg. 2004 Jun;39(6):1200-8. doi: 10.1016/j.jvs.2004.02.039.

  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

• Healy D, Clarke-Moloney M, Gaughan B, O'Daly S, Hausenloy D, Sharif F, Newell J, O'Donnell M, Grace P, Forbes JF, Cullen W, Kavanagh E, Burke P, Cross S, Dowdall J, McMonagle M, Fulton G, Manning BJ, Kheirelseid EA, Leahy A, Moneley D, Naughton P, Boyle E, McHugh S, Madhaven P, O'Neill S, Martin Z, Courtney D, Tubassam M, Sultan S, McCartan D, Medani M, Walsh S. Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial. Trials. 2015 Apr 23;16:185. doi: 10.1186/s13063-015-0678-1.

  PMID: 25903752 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

Central Study Contacts

Stewart R Walsh, MCh FRCS

CONTACT

00353 876632654; stewart.walsh@ul.ie

Mary Clarke Moloney, PhD

CONTACT

0035361482736; mary.clarkemoloney@hse.ie

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: Prefessor Stewart Walsh

Study Record Dates

• First Submitted: March 24, 2014
• First Posted: March 26, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2017
• Last Updated: December 12, 2014

Record last verified: 2014-12

Locations

IE (6)