Preconditioning Shields Against Vascular Events in Surgery (SAVES-F)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Mid Western Regional Hospital, Ireland
Sponsor:
Information provided by (Responsible Party):
Professor Stewart Walsh, Mid Western Regional Hospital, Ireland
ClinicalTrials.gov Identifier:
NCT02097186
First received: March 24, 2014
Last updated: March 25, 2014
Last verified: March 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 ischaemic 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 Feasibility Trial of Preconditioning Against Adverse Events in Major Vascular Surgery (Preconditioning-SAVES)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Serum troponin levels [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Composite 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.

  • 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.

  • Post-operative complications [ Time Frame: 30 day ] [ Designated as safety issue: No ]
    Postoperative complications will be recorded and results from both groups compared.

  • Mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Death within one year of surgery will be determined by contacting the patient's general practitioner.

  • Cardiac or cerebral event [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Major adverse cardiac or cerebral event (myocardial infarction, cardiac death, cerebrovascular accident) within 1 year of surgery will be determined by contacting the patient's general practitioner for details.

  • Acute upper limb ischaemia [ Time Frame: 24 hours post-operatively ] [ Designated as safety issue: Yes ]
    Acute upper limb ischaemia - This is defined as the development of ischaemia in the arm used for the preconditioning stimulus requiring systemic anti-coagulation, radiological intervention or surgical intervention. The arm will be assessed at the end of surgery to identify if ischaemia is present.

  • Acute upper limb deep vein thrombosis [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
    Acute upper limb deep vein thrombosis - This is defined as the development of thrombus within the subclavian, axillary or brachial vein, which may develop up to 10 days post procedure, confirmed in duplex ultrasound and in the same arm as used for the RIPC stimulus.

  • Serial troponin I results [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    A comparison of the area under the curve of serial troponin I


Other Outcome Measures:
  • Acceptability of RIPC to patients [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    For patients, particularly those undergoing regional anaesthesia rather than general, the intervention may be burdensome and uncomfortable which may negatively impact upon likely adoption of this intervention into routine practice.In order to explore these potential issues, this feasibility trial will include a qualitative evaluation of acceptability to patients together with a qualitative evaluation of any perceived barriers to implementation. This evaluation will take the form of a semi-structured phone interview.

  • Acceptability and barriers to implementation among healthcare professionals. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Healthcare professionals at participating practices will be asked to complete a self-administered electronic questionnaire at the end of the study period. The questionnaire will elicit data on profession and practice details, their perceived experience of trial involvement, and open-ended questions to elicit information regarding attitudes to trial involvement, willingness to recruit participants, difficulties that arose during the trial and potential barriers to further research or routine clinical use of the trial intervention.


Estimated Enrollment: 400
Study Start Date: April 2014
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Procedure: 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.
Other Name: RIPC
No Intervention: Control to remote preconditioning group
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:

  • 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
  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: NCT02097186

Contacts
Contact: Stewart R Walsh, MCh FRCS 00353 876632654 stewart.walsh@ul.ie
Contact: Mary Clarke Moloney, PhD 0035361482736 mary.clarkemoloney@hse.ie

Locations
Ireland
Cork University Hospital Not yet recruiting
Cork, Ireland, 000
Contact: Greg Fulton       greg.fulton@hse.ie   
Principal Investigator: Greg Fulton         
Sub-Investigator: Brian Manning         
Beaumont Hospital Not yet recruiting
Dublin, Ireland, 000
Contact: Darragh Moneley    0035301809 3092      
Principal Investigator: Darragh Moneley         
Sub-Investigator: Austin Leahy         
St James's Hospital Not yet recruiting
Dublin, Ireland, 000
Contact: Prakash Madhavan       pmadhavan@stjames.ie   
Principal Investigator: Prakash Madhavan         
Sub-Investigator: Zenia Martin         
Sub-Investigator: Dermot Moore         
Sub-Investigator: Sean O'Neill         
University Hospital Limerick (AKA MidWestern Regional Hospital) Not yet recruiting
Limerick, Ireland, 000
Contact: Mary Clarke Moloney, PhD    0035361482736    mary.clarkemoloney@hse.ie   
Sub-Investigator: Mary Clarke Moloney, PhD.         
Principal Investigator: Eamon Kavanagh         
Sub-Investigator: Paul Burke         
Waterford Regional Hospital Not yet recruiting
Waterford, Ireland, 000
Contact: Simon Cross         
Principal Investigator: Simon Cross         
Sub-Investigator: Joseph Dowdall         
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, Prefessor Stewart Walsh, Mid Western Regional Hospital, Ireland
ClinicalTrials.gov Identifier: NCT02097186     History of Changes
Other Study ID Numbers: SAVES-F
Study First Received: March 24, 2014
Last Updated: March 25, 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 October 21, 2014