Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot

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.

Study Overview

• Status: Unknown
• Conditions: Cardiac Arrest
• Intervention / Treatment: Device: Active Remote Ischemic Conditioning; Device: Sham Remote Ischemic Conditioning

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Graham Nichol, MD, MPH; Phone Number: 206-521-1722; Email: ricstudy@uw.edu
• Study Contact Backup: Name: Emily Bartlett, MD; Phone Number: 206 521 1722; Email: ricstudy@uw.edu

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Graham Nichol
      • Contact: Graham Nichol, MD MPH; Phone Number: 206-521-1722; Email: ricstudy@uw.edu
      • Contact: Emily S Bartlett, MD MS; Email: ricstudy@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Included will be those with:

1. Age 18 years or more;
2. Defibrillation by laypersons or defibrillation and/or chest compressions by EMS providers dispatched to the scene;
3. Non-traumatic etiology of arrest, defined as without concomitant blunt, penetrating, or burn-related injury, or uncontrolled bleeding or exsanguination;
4. Spontaneous circulation upon emergency department arrival;
5. No response to verbal commands; and
6. Ongoing or planned induced hypothermia.

Excluded will be those with:

1. 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;
2. Written do not attempt resuscitation (DNAR) reported to providers before randomization;
3. Drowning or hypothermia as cause of arrest;
4. Known prisoner or pregnant; or
5. Dialysis fistula in either upper extremity; or
6. Pre-existing amputation of upper extremity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intervention Group; 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; 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.
SHAM_COMPARATOR: Control Group; 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; 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.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Failure	device failure will be defined as discontinuation of use of the device prior to the end of allocated treatment interval because of mechanical failure as opposed to provider preference.	30 minutes from initiation of study intervention
Expected Adverse Event Related to Device- Pain	Pain assessed using the Richmond Agitation-Sedation Scale at 30 and 60 minutes after randomization in control and intervention group patients. No gold standard exists for pain assessment in sedated and ventilated patients.	Within 24 hours of Enrollment
Expected Adverse Event Related to Device- Thrombophlebitis	Thrombophlebitis assessed as symptomatic non central nervous system venous or arterial thrombus documented radiographically or ultrasonographically in the upper extremity to which the study intervention was applied.	Within 1 week of Enrollment
Expected Adverse Event Related to Device- Sepsis	Sepsis assessed within one week of index arrest as either i) the presence of microbiologically proven, clinically proven, or suspected infection; or ii) presence of Systemic Inflammatory Response Syndrome (SIRS); and iii) development of at least one organ dysfunction within the preceding 24 hours.	Within 1 week of Enrollment
Expected Adverse Event Related to Cardiac Arrest	Related to Cardiac Arrest The following are commonly observed in patients who experience cardiac arrest, and may or may not be attributable to specific resuscitation therapies. These will be monitored and reported but not classified as serious adverse events. Clinical diagnoses of pneumonia, cerebral bleeding, stroke, seizures, bleeding requiring transfusion or surgical intervention, rearrest, pulmonary edema, serious rib fractures, sternal fractures, internal thoracic or abdominal injuries as noted in the hospital discharge summary.	Discharge or 30 days after index arrest
Unexpected Adverse Event	These will be defined as any serious unexpected adverse effect on health or safety or any unexpected life-threatening problem caused by, or associated with, a device, if that effect or problem was not previously identified in nature, severity, or degree of incidence in the investigation plan or application, or any other unexpected serious problem associated with a device that relates to the rights, safety or welfare of subjects. Death or neurological impairment will not be considered an adverse event in this study, as it is an expected part of the natural history of the illness for a large proportion of the population.	Discharge or 30 days after index arrest

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Kettering Foundation; ZOLL Foundation
• Investigators: Principal Investigator: Emilby S Bartlett, MD MS, University of Washington

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 7, 2020
• Primary Completion (ANTICIPATED): August 7, 2020
• Study Completion (ANTICIPATED): January 7, 2021

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (ACTUAL): February 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; reperfusion injury
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest
• Other Study ID Numbers: STUDY00005176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Available upon request, subject to mutual agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No