RCT to Evaluate the Renal Protective Effects of Remote Ischaemic Preconditioning in Peripheral Angioplasty

Sponsor

Mid Western Regional Hospital, Ireland (Other)

Overall Status

Unknown status

CT.gov ID

NCT02054871

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aims to demonstrate if remote ischaemic preconditioning (RIPC) may confer renal protection in patients undergoing peripheral angioplasty. Patients will be randomised to receive RIPC and biomarkers for renal injury will be analysed post procedure to determine if any protective benefit was obtained.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Vascular Disease	Procedure: RIPC	N/A

Detailed Description

Ischaemic preconditioning is an endogenous mammalian mechanism whereby a brief period of ischaemia and reperfusion confers resistance to subsequent prolonged ischaemic insults. First observed in the canine heart, subsequent investigators noted that brief ischaemia in remote organs e.g. skeletal muscle, induced protection in key central organs e.g. the heart. This remote ischaemic preconditioning (RIPC) does not require direct interference with the target organs' blood supply. It can be induced using blood pressure cuffs to produce brief episodes of upper limb ischaemia and reperfusion and confers protection upon numerous organs simultaneously. RIPC reduces myocardial injury following aortic aneurysm repair, cardiac surgery and angioplasty. It also reduces adverse ischaemic events up to six months following percutaneous coronary intervention, implying some medium-term effect.

To date ischaemic conditioning has been applied primarily to the heart however animal studies have shown pre conditioning to offer renal protection.

Fikret et al in 2012 in the Renal Protection Trial demonstrated a protective benefit with RIPC from the development of CIN in high risk patients undergoing elective coronary angiography.Whittaker and Przyklenk in 2011 explored this concept retrospectively using data from patients who had undergone emergency angioplasty for ST elevation myocardial infarction. The original trial was a RCT which examined the protective effect of postconditioning on myocardial ischemia. The authors retrospectively examined if study patients treated with multiple coronary balloon inflations had better renal function than patients not exposed to this remote conditioning. They concluded that patients in the conditioning group received 25% more contrast volume than the control group and showed no decline in renal function as demonstrated by examination of glomular filtration rate at day 3 post procedure in comparison to the control group which saw a significant decline in renal function. The need for contrast-based procedures is rising, with increasing numbers of patients undergoing endovascular procedures, as is the incidence of postcontrast renal failure, which has a reported mortality of 34%. The potential use of RIPC therefore to reduce the risk of kidney damage needs further investigation in a prospective study and the PAD patient group who are routinely exposed to contrast administration in angiography are an ideal study group.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomised Controlled Trial to Evaluate the Reno-protective Benefits of Remote Ischaemic Preconditioning in Patients Undergoing Infrainguinal Peripheral Angioplasty

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Jul 1, 2014

Anticipated Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EGFR 30-60 Experimental: RIPC Remote preconditioning Calculated EGFR based on MDRD. Patients receive intravenous fluids preprocedure as additional renal protection. Preconditioning will be performed in the same manner as several previous trials. Immediately prior to angiography a 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.	Procedure: RIPC 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 3 ischaemia-reperfusion cycles. Additional, blood and urine samples will be collected on Day 1, Day 2 and Day 3 post procedure.
Experimental: EGFR 60-90 Experimental: RIPC Remote preconditioning. EGFR calculated using MDRD equation. Oral hydration pre-procedural as reno-protective measure. Preconditioning will be performed in the same manner as several previous trials. Immediately prior to angiography a 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.	Procedure: RIPC 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 3 ischaemia-reperfusion cycles. Additional, blood and urine samples will be collected on Day 1, Day 2 and Day 3 post procedure.
No Intervention: EGRF 30-60 No Intervention: Remote preconditioning control Calculated EGFR based on MDRD. Patients receive intravenous fluids preprocedure as additional renal protection. Patients randomised to this group will receive routine care.
No Intervention: EGRF 60-90 No Intervention: Remote preconditioning control EGFR calculated using MDRD equation. Oral hydration pre-procedural as reno-protective measure. Patients randomised to this group will receive routine care.

Outcome Measures

Primary Outcome Measures

Renal impairment [72 hours post procedural]
Serial assessment of renal biomarkers in serum and urine in 72 hour period post procedure

Secondary Outcome Measures

Anti-inflammatory effect of RIPC [3-6 months post recruitment]
Assessment of additional postulated benefits of anti-inflammatory effects with RIPC in terms of decreased restenosis rates and lower inflammatory markers

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Elective intra-arterial, infrainguinal peripheral angiography/angioplasty
Written informed consent
Patients >18yrs of age
Patients with CKD (Stage2/3) as evidenced by eGFR <90ml/min/1.73m2

Exclusion Criteria:

Severe renal impairment eGFR <30ml/min
Evidence of acute renal failure or patients on dialysis
History of previous CIN
Contraindication to intravenous volume replacement therapy
Pregnancy
Patients on glibenclamide or nicorandil (these medications may interfere with RIPC)