Interest of Remote Ischemic Preconditioning for Prevention of Contrast Medium-induced Nephropathy in High Risk Patients

Study Overview
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Brief Summary
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Diagnostic imaging for vascular investigations and endovascular procedures frequently require the use of contrast medium. Besides contrast medium-induced hypersensitivity, an acute kidney injury can appear: the contrast-induced nephropathy (NPCI). NPCI is associated with an increase of patients' morbidity and mortality. One of the conventional methods proposed to limit this NPCI is an oral administration of N-acetylcysteine (NAC) associated with hydration performed 12 hours before and 12 hours after the injection. However, in some patients this method cannot be performed due to a high risk of heart failure although they are generally at high risk of NPCI. Recently, it has been shown, in a randomized trial, that remote ischemic preconditioning (several cycles of upper-arm ischemia-reperfusion with a pressure cuff inflator) associated with hydratation and NAC reduced the occurrence of NPCI after a coronary angiography as compared with NAC and hydration only. . We hypothesized that the use of RIPC in patients at high risk of NPCI and who cannot receive NAC and hydratation (e.g. patients with aortic stenosis and eligible for Transcatheter Aortic Valve Implantation (TAVI)) could be promising.

Detailed Description
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Study design : Prospective, single-center, randomized, controlled, single-blind, with RIPC procedure (Pre-CI) versus SHAM ischemic preconditioning (SHAM Pre -CI) (control). This test will follow the CONSORT Statement (http://www.consort-statement.org/). This is a randomized, controlled, single-blind trial, assessing the incidence of NPCI (after a CTA ) between two group of patients, one receiving RIPC procedure and the other group receiving a SHAM RIPC (control group). RIPC is accomplished by performing 4 cycles of alternating 5-minute inflation and 5-minute deflation of a standard upper-arm blood pressure cuff, to induce transient and repetitive arm ischemia and reperfusion. RIPC will be started just before the CTA, and the time between the last inflation cycle and the beginning of the CTA will be less than 45 minutes. The SHAM RIPC will be carried out with the same number of cycles that the RIPC but cuff will be inflated to the diastolic pressure of the subject and the cuff will be deflated to10 mmHg in order to maintain a non- ischemic compression (blind patient protocol). Main objective : To assess the efficacy of remote ischemic preconditioning (RIPC) in preventing contrast-induced nephropathy (NPCI) after injected CT scanner in patients at high risk of NPCI. Secondary objectives : To assess the effects of RIPC on a second marker of renal failure (Cystatin C ) ; To determine the pathophysiological mechanisms involved in the RIPC (role of oxidative stress ; for the first 40 patients) ; To assess the effect of RIPC on renal function after a second injection of contrast-medium during coronary angiography performed 2 to 4 days after the injected CTA ; To assess the tolerance of RIPC procedure ; To assess the impact on mortality at 6 months.

Official Title
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IPC-Angio Trial : Interest of Remote Ischemic Preconditioning for Prevention of Contrast Medium-induced Nephropathy (Post-diagnostic Imaging) in Patients at High Risk of Contrast-induced Nephropathy

Conditions
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Nephropathy

Intervention / Treatment
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* Other: Remote Ischemic Preconditioning (RIPC)
* Other: SHAM Remote Ischemic Preconditioning (SHAM RIPC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years, no upper age limit ; Patient which may hospitalized for a medical check-up before a percutaneous aortic valve implantation (CTA and coronarography); Patient at risk for NPCI defined by a Mehran risk classification system ≥11 (Annexe 2) ; Willing to provide free and informed written consent Exclusion Criteria: Pathology of the upper-limbs limiting the use of the cuff (bilateral amputation, arteriovenous fistula); Critical renal disease requiring hemodialysis ; Person who is not affiliated to a health care system insurance Inability to understand the instructions of the study; Absolute contraindication to of iodinated contrast medium injection (anaphylactic shock history to contrast media, especially Xenetix, clearance (MDRD) less than 30mL/min/1.73m2) ; Pregnancy Simultaneous participation in other protocol; Person with legal protection, person deprived of liberty.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote ischemic preconditioning<br>Remote Ischemic Preconditioning (RIPC) is accomplished by performing 4 cycles of alternating 5-minute inflation and 5-minute deflation of a standard upper-arm blood pressure cuff, to induce transient and repetitive arm ischemia and reperfusion. RIPC will be started just before the CTA, and the time between the last inflation cycle and the beginning of the CTA will be less than 45 minutes. | Other: Remote Ischemic Preconditioning (RIPC)<br>* RIPC is accomplished by performing 4 cycles of alternating 5-minute inflation and 5-minute deflation of a standard upper-arm blood pressure cuff, to induce transient and repetitive arm ischemia and reperfusion. RIPC will be started just before the CTA, and the time between the last inflation cycle and the beginning of the CTA will be less than 45 minutes.<br>|
| Sham Comparator: SHAM remote ischemic preconditioning<br>The SHAM Remote Ischemic Preconditioning (SHAM RIPC) will be carried out with the same number of cycles that the RIPC but cuff will be inflated to the diastolic pressure of the subject and the cuff will be deflated to10 mmHg in order to maintain a non- ischemic compression (blind patient protocol). | Other: SHAM Remote Ischemic Preconditioning (SHAM RIPC)<br>* The SHAM Remote Ischemic Preconditioning (SHAM RIPC) will be carried out with the same number of cycles that the RIPC but cuff will be inflated to the diastolic pressure of the subject and the cuff will be deflated to10 mmHg in order to maintain a non- ischemic compression (blind patient protocol).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of NPCI | Incidence of NPCI defined as an increase in serum creatinine ≥ 0.5 mg / dL or a relative increase of 25 % above baseline at 48 hours after contrast medium exposure. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cystatin C | Changes of serum Cystatin C between day 0 and day 1, and day 0 and day 2. | 2 days | 
| Oxydative stress | Changes in markers of oxydative stress (in the first 40 patients included) : at day 0, after the RIPC procedure or SHAM-RIPC procedure (+ 5 min) before CTA ; after CTA (+ 30 min) and 24 hours after CTA (day 1). | 24 hours | 
| Renal function | Changes in serum creatinine and Cystatin C between day 0 and measured values after coronarography (day 6 ). | 6 days | 
| Pain | A standardized pain scale (ranged from 0 to 10; 0 : no pain; 10 : maximum of pain). | Day 0 | 
| Mortality | Assessment of mortality at six months. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter Aortic Valve Implantation