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

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

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.

Study Overview

• Status: Unknown
• Conditions: Peripheral Vascular Disease
• Intervention / Treatment: Procedure: RIPC

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kamsila Pillay, MbCHB; Email: kamsilakp@yahoo.co.uk

Study Locations

• Ireland
  • Limerick, Ireland
    • Recruiting
    • HSE Mid Western Regional Hospital
    • Contact: Kamsila Pillay; Email: kamsilakp@yahoo.co.uk
    • Sub-Investigator: Kamsila Pillay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal impairment	Serial assessment of renal biomarkers in serum and urine in 72 hour period post procedure	72 hours post procedural

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-inflammatory effect of RIPC	Assessment of additional postulated benefits of anti-inflammatory effects with RIPC in terms of decreased restenosis rates and lower inflammatory markers	3-6 months post recruitment

Collaborators and Investigators

• Sponsor: Mid Western Regional Hospital, Ireland
• Investigators: Principal Investigator: Stewart Walsh, MCh FRCS, University of Limerick

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): July 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: February 3, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: February 3, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Peripheral Angioplasty; Remote Ischaemic Preconditioning; Contrast Induced Nephropathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: MWRH09644

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No