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Preconditioning Shields Against Vascular Events in Surgery (SAVES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Mid Western Regional Hospital, Ireland
Sponsor:
Information provided by (Responsible Party):
Professor Stewart Walsh, Mid Western Regional Hospital, Ireland
ClinicalTrials.gov Identifier:
NCT01691911
First received: September 13, 2012
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Abdominal Aortic Aneurysm
Carotid Atherosclerosis
Critical Lower Limb Ischaemia
Procedure: Remote preconditioning

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Preconditioning Shields Against Vascular Events in Surgery. A Multi-Centre Trial of Preconditioning Against Adverse Events in Major Vascular Surgery

Resource links provided by NLM:


Further study details as provided by Mid Western Regional Hospital, Ireland:

Primary Outcome Measures:
  • Major Adverse Clinical Events [ Time Frame: 30 day ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of post-operative hospital stay [ Time Frame: 30 day ] [ Designated as safety issue: No ]
    The duration of hospital stay and ITU stay have a major impact on health service resource utilisation, and are factors which can be influenced by surgery.

  • Duration of intensive care unit stay [ Time Frame: 30 day ] [ Designated as safety issue: No ]
    The duration of hospital stay and ITU stay have a major impact on health service resource utilisation, and are factors which can be influenced by surgery.

  • Unplanned critical care unit admission [ Time Frame: 30 day ] [ Designated as safety issue: No ]
    The duration of hospital stay and ITU stay have a major impact on health service resource utilisation, and are factors which can be influenced by surgery.

  • Acute kidney injury score in first three peri-operative days [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    The Acute Kidney Injury Score will be calculated over the first three peri-operative days. Creatinine will be measured daily as part of routine care. Urine volumes will be calculated from the fluid balance charts maintained as part of usual care.

  • Peri-operative myocardial injury [ Time Frame: from operation to 72 hours postoperatively ] [ Designated as safety issue: No ]
    Peri-operative myocardial injury will be assessed by measurement of serum troponin levels. This will be achieved by comparing area under the curve (AUC) for serum troponin concentration over the first three post-operative days.


Estimated Enrollment: 1900
Study Start Date: February 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Remote preconditioning
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
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.
No Intervention: Remote preconditioning control
Patients randomised to this group will receive routine pre-operative, peri-operative and post operative care.

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691911

Contacts
Contact: Stewart R Walsh, MCh FRCS 00353 876632654 stewart.walsh@ul.ie

Locations
Ireland
MidWestern Regional Hospital Recruiting
Limerick, Ireland, 000
Contact: Mary Clarke Moloney, Ph.D    00353 61482736 ext 2736    mary.clarkemoloney@hse.ie   
Contact: Stewart R Walsh, MCh FRCS    00353 876632654    stewart.walsh@ul.ie   
Sub-Investigator: Mary Clarke Moloney, Ph.D.         
Sponsors and Collaborators
Mid Western Regional Hospital, Ireland
Investigators
Principal Investigator: Stewart R Walsh, MCh FRCS Mid Western Regional Hospital and University of Limerick
  More Information

Publications:

Responsible Party: Professor Stewart Walsh, Mid Western Regional Hospital, Ireland
ClinicalTrials.gov Identifier: NCT01691911     History of Changes
Other Study ID Numbers: SAVES-123
Study First Received: September 13, 2012
Last Updated: April 29, 2014
Health Authority: Ireland: Research Ethics Committee

Keywords provided by Mid Western Regional Hospital, Ireland:
Vascular disease
Open aortic aneurysm repair
Endovascular aneurysm repair
Carotid endartrectomy
Lower limb surgical revascularisation
Major lower limb amputation

Additional relevant MeSH terms:
Aneurysm
Aortic Aneurysm
Aortic Aneurysm, Abdominal
Arteriosclerosis
Atherosclerosis
Carotid Artery Diseases
Aortic Diseases
Arterial Occlusive Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014