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

Peripheral Vascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02054871
• Other study ID #: MWRH09644
• Status: Recruiting
• Phase: N/A
• First received: February 3, 2014
• Last updated: February 3, 2014
• Start date: September 2013
• Est. completion date: August 2014

Study information

• Verified date: February 2014
• Source: Mid Western Regional Hospital, Ireland
• Contact: Kamsila Pillay, MbCHB
• Email: kamsilakp[@]yahoo.co.uk
• Is FDA regulated: No
• Health authority: Ireland: Health Service Executive
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

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.

Locations

Country	Name	City	State
Ireland	HSE Mid Western Regional Hospital	Limerick

Sponsors (1)

Lead Sponsor	Collaborator
Mid Western Regional Hospital, Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal impairment	Serial assessment of renal biomarkers in serum and urine in 72 hour period post procedure	72 hours post procedural	No
Secondary	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	No