Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot

Study Overview
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Brief Summary
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Following resuscitation from out-of-hospital cardiac arrest (OHCA), reperfusion injury can cause cell damage in the heart and brain. Remote ischemic conditioning (RIC) consists of intermittent application of a device such as a blood pressure cuff to a limb to induce non-lethal ischemia. Studies in animals with cardiac arrest as well as in humans with acute myocardial infarction suggest that RIC before or after restoration of blood flow may reduce injury to the heart and improve outcomes but this has not been proven in humans who have had OHCA. The RICE pilot study is a single-center study to assess the feasibility of application of RIC in the emergency department setting for patients transported to the hospital after resuscitation from OHCA.

Official Title
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Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot

Conditions
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Cardiac Arrest

Intervention / Treatment
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* Device: Active Remote Ischemic Conditioning
* Device: Sham Remote Ischemic Conditioning


Participation Criteria
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Eligibility Criteria
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Included will be those with: Age 18 years or more; Defibrillation by laypersons or defibrillation and/or chest compressions by EMS providers dispatched to the scene; Non-traumatic etiology of arrest, defined as without concomitant blunt, penetrating, or burn-related injury, or uncontrolled bleeding or exsanguination; Spontaneous circulation upon emergency department arrival; No response to verbal commands; and Ongoing or planned induced hypothermia. Excluded will be those with: STEMI indicated on first 12-lead ECG obtained after restoration of circulation, defined as ST-elevation of ≥2 mm in two or more contiguous ECG leads; Written do not attempt resuscitation (DNAR) reported to providers before randomization; Drowning or hypothermia as cause of arrest; Known prisoner or pregnant; or Dialysis fistula in either upper extremity; or Pre-existing amputation of upper extremity.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention Group<br>A standard non-invasive blood pressure cuff (e.g., American Diagnostics Corporation, Hauppauge, NY but any one can be used off the shelf) and disposable plastic clamp (e.g.,Medline Industries Incorporated, Mundelein, IL) can be used to apply RIC in patients resuscitated from OHCA via three cycles of 5-mins. inflation to 200 mmHg followed by 5-mins. deflation of a blood pressure cuff on an upper extremity. The cuff occludes the artery; the clamp maintains pressure in the air bladder of the cuff during the inflation periods. | Device: Active Remote Ischemic Conditioning<br>* A standard non-invasive blood pressure cuff (e.g., American Diagnostics Corporation, Hauppauge, NY but any one can be used off the shelf) and disposable plastic clamp (e.g.,Medline Industries Incorporated, Mundelein, IL) can be used to apply RIC in patients resuscitated from OHCA via three cycles of 5-mins. inflation to 200 mmHg followed by 5-mins. deflation of a blood pressure cuff on a upper extremity. The cuff occludes the artery; the clamp maintains pressure in the air bladder of the cuff during the inflation periods.<br>|
| Sham Comparator: Control Group<br>The control group will have a sham package opened at the bedside as soon as feasible after ED arrival. This will be identical in size, weight and appearance as that in the intervention group, but will contain a sham device. Upon identification that the patient has been randomized to the control group, the care team will proceed with all other resuscitative measures as in the the intervention group. | Device: Sham Remote Ischemic Conditioning<br>* The control group will have a sham package opened at the bedside as soon as feasible after ED arrival. This will be identical in size, weight and appearance as that in the intervention group, but will contain a sham device. Upon identification that the patient has been randomized to the control group, the care team will proceed with all other resuscitative measures as in the the intervention group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attrition | Attrition assessed as the proportion of randomized subjects who do not remain on allocated therapy for the intended study duration among subjects randomly allocated. On therapy for the intended study duration consists of completing three cycles of inflation-deflation. | 30 minutes from initiation of study intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Success | Treatment Success assessed as the proportion of intervention group patients who remain alive and on their allocated therapy for the intended study duration. | 30 minutes from initiation of study intervention | 
| Cardiac Function | Cardiac Function assessed as left ventricular ejection fraction (LVEF) using echocardiograms ordered for clinical indications. | Within 48 hours of index arrest | 
| Cardiogenic Shock | Cardiogenic Shock assessed as systolic BP < 80 mmHg during any 6 h period within 48 h of the index arrest not due to a correctable cause, and treated with pressors or inotropes or placement of a mechanical cardiac assist device (e.g. intra-aortic balloon pump). Cardiogenic shock correlates with survival after resuscitation from cardiac arrest. | Within 48 hours of index arrest | 
| STEMI | STEMI assessed as the presence of electrocardiographic (ECG) and biomarker criteria for acute myocardial infarction within 48 h of the index arrest. Note that ST-elevation on the first 12-lead ECG after resuscitation is a poor predictor of acute infarction in this population. These patients often develop infarctions during the subsequent 48 h. | Within 48 hours of index arrest | 
| Myocardial Injury | Myocardial Injury assessed as peak serum troponin in ng/mL at any time point within 24 h of index arrest. | Within 24 hours of index arrest | 
| Renal Dysfunction | Renal Dysfunction assessed using Risk, Injury, Failure, Loss, End Stage criteria. | Within 24 hours of index arrest | 
| Hospital Free Survival | Hospital Free Survival (HFS) assessed as number of days alive and permanently out of hospital up to 30 days post arrest | Within 30 days of index arrest | 
| Withdrawal of Care | assessed as the reduction of support (i.e. reducing pressors, lab draws or medications) or withdrawal of support (i.e. extubation, stopping drips/meds, changing to comfort care only) during hospitalization. | Discharge or 30 days after index arrest | 
| Favourable Neurologic Status at Discharge | Favourable Neurologic Status at Discharge assessed using modified Rankin Score (MRS) < 3 at hospital discharge or 30 days after index arrest. | Discharge or 30 days after index arrest | 
| Survival to Discharge | Survival to Discharge assessed as alive when discharged from hospital to home, nursing facility or rehabilitation. Patients transferred to another acute care facility (e.g. to undergo implantable defibrillator placement) will be considered still hospitalized. | Dicharge or 30 days after index arrest | 
| Clinical Instability at Discharge | Clinical Instability at Discharge assessed using the Kosecoff Index measured at discharge based on the presence of nine symptoms and signs associated with increased risk of rehospitalization. Instability will be the presence of any of these. | Discharge or 30 days after index arrest | 
| Survival to 30 days after arrest | Survival to 30 Days After Cardiac Arrest assessed as alive 30 days after the index cardiac arrest as confirmed by a brief telephone interview. | 30 days after index arrest | 
| Accrual | Accrual is the proportion of eligible subjects who have the study device applied | Through study completion, an average of 6 mos. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reperfusion injury, remote ischemic conditioning