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Preconditioning Shields Against Vascular Events in Surgery

NCT ID: NCT02097186

Last Updated: 2014-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2017-08-31

Brief Summary

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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.

Detailed Description

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The demand for major vascular surgery is increasing \[1\]. Patients requiring procedures such as aortic aneurysm repair, carotid endarterectomy, lower limb surgical re-vascularisation and major lower limb amputation for end-stage vascular disease constitute a high-risk surgical cohort. Peri-operative complications such as myocardial infarction, cerebrovascular accident, renal failure and death are common \[2,3\]. Multiple potential mechanisms may result in these complications. For example, myocardial injury may result from systemic hypotension leading to reduced flow across a tight coronary artery stenosis or, alternatively, it may arise due to acute occlusion when an unstable plaque ruptures. Most strategies aimed at peri-operative risk reduction target a single potential mechanism. For example, beta-blockade may prevent myocardial injury due to overwork, but cannot prevent acute coronary occlusion. There is a requirement for a simple, effective intervention that protects tissues against injury via multiple different mechanisms. Remote ischemic preconditioning (RIPC) may be suitable.

Ischemic preconditioning is a phenomenon whereby a brief period of non-lethal ischemia in a tissue renders it resistant to the effects of a subsequent much longer ischaemic insult. It was first described in the canine heart \[4\]. Subsequent clinical trials showed that ischemic preconditioning reduced heart muscle damage following coronary artery bypass grafting \[5\] and liver dysfunction following hepatic resection \[6\]. Following cardiac surgery, it is associated with a reduction in critical care stay, arrhythmias and inotrope use \[7\]. However, ischemic preconditioning requires direct interference with the target tissues' blood supply, limiting its clinical utility. Further experimental work suggested that brief ischemia in one tissue, such as the kidneys, could confer protection on distant organs such as the heart \[8\]. A similar effect was observed after transient skeletal muscle ischemia \[9-11\]. This effect is referred to as 'preconditioning at a distance' or 'remote ischemic preconditioning' (RIPC).

Conditions

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Abdominal Aortic Aneurysm Carotid Atherosclerosis Critical Lower Limb Ischaemia

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Remote ischaemic preconditioning

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.

Group Type EXPERIMENTAL

Remote ischaemic preconditioning

Intervention Type 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.

Control to remote preconditioning group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Remote ischaemic preconditioning

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.

Intervention Type PROCEDURE

Other Intervention Names

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RIPC

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mid Western Regional Hospital, Ireland

OTHER

Sponsor Role lead

Responsible Party

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Professor Stewart Walsh

Prefessor Stewart Walsh

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stewart R Walsh, Mch FRCS

Role: PRINCIPAL_INVESTIGATOR

Mid Western Regional Hospital and University of Limerick

Locations

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Cork University Hospital

Cork, Cork, Ireland

Site Status NOT_YET_RECRUITING

Beaumont Hospital

Dublin, Dublin, Ireland

Site Status RECRUITING

St James's Hospital

Dublin, Dublin, Ireland

Site Status RECRUITING

University Hospital Limerick (AKA MidWestern Regional Hospital)

Limerick, Limerick, Ireland

Site Status RECRUITING

Waterford Regional Hospital

Waterford, Waterford, Ireland

Site Status RECRUITING

University Hospital Galway

Galway, , Ireland

Site Status RECRUITING

Countries

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Ireland

Central Contacts

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Stewart R Walsh, MCh FRCS

Role: CONTACT

Phone: 00353 876632654

Email: [email protected]

Mary Clarke Moloney, PhD

Role: CONTACT

Phone: 0035361482736

Email: [email protected]

Facility Contacts

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Greg Fulton

Role: primary

Darragh Moneley

Role: primary

Prakash Madhavan

Role: primary

Mary Clarke Moloney, PhD

Role: primary

Simon Cross

Role: primary

Stewart R Walsh

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 15192558 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16235289 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15351191 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3769170 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9155608 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14631221 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18783958 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7680290 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9315559 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12460865 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9362234 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25903752 (View on PubMed)

Other Identifiers

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SAVES-F

Identifier Type: -

Identifier Source: org_study_id