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Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot

Primary Purpose

Cardiac Arrest

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Active Remote Ischemic Conditioning
Sham Remote Ischemic Conditioning
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Arrest focused on measuring reperfusion injury, remote ischemic conditioning

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Graham NicholRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Intervention Group

Control Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Cardiac Function
Cardiac Function assessed as left ventricular ejection fraction (LVEF) using echocardiograms ordered for clinical indications.
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.
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.
Myocardial Injury
Myocardial Injury assessed as peak serum troponin in ng/mL at any time point within 24 h of index arrest.
Renal Dysfunction
Renal Dysfunction assessed using Risk, Injury, Failure, Loss, End Stage criteria.
Hospital Free Survival
Hospital Free Survival (HFS) assessed as number of days alive and permanently out of hospital up to 30 days post 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.
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.
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.
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.
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.
Accrual
Accrual is the proportion of eligible subjects who have the study device applied

Full Information

First Posted
January 15, 2020
Last Updated
February 7, 2020
Sponsor
University of Washington
Collaborators
Kettering Foundation, ZOLL Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04265807
Brief Title
Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot
Official Title
Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 7, 2020 (Anticipated)
Primary Completion Date
August 7, 2020 (Anticipated)
Study Completion Date
January 7, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Kettering Foundation, ZOLL Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Arrest
Keywords
reperfusion injury, remote ischemic conditioning

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Patients and investigators will be masked to treatment assignment up to the point of randomization.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Control Group
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active Remote Ischemic Conditioning
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham Remote Ischemic Conditioning
Intervention Description
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.
Primary Outcome Measure Information:
Title
Attrition
Description
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.
Time Frame
30 minutes from initiation of study intervention
Secondary Outcome Measure Information:
Title
Treatment Success
Description
Treatment Success assessed as the proportion of intervention group patients who remain alive and on their allocated therapy for the intended study duration.
Time Frame
30 minutes from initiation of study intervention
Title
Cardiac Function
Description
Cardiac Function assessed as left ventricular ejection fraction (LVEF) using echocardiograms ordered for clinical indications.
Time Frame
Within 48 hours of index arrest
Title
Cardiogenic Shock
Description
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.
Time Frame
Within 48 hours of index arrest
Title
STEMI
Description
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.
Time Frame
Within 48 hours of index arrest
Title
Myocardial Injury
Description
Myocardial Injury assessed as peak serum troponin in ng/mL at any time point within 24 h of index arrest.
Time Frame
Within 24 hours of index arrest
Title
Renal Dysfunction
Description
Renal Dysfunction assessed using Risk, Injury, Failure, Loss, End Stage criteria.
Time Frame
Within 24 hours of index arrest
Title
Hospital Free Survival
Description
Hospital Free Survival (HFS) assessed as number of days alive and permanently out of hospital up to 30 days post arrest
Time Frame
Within 30 days of index arrest
Title
Withdrawal of Care
Description
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.
Time Frame
Discharge or 30 days after index arrest
Title
Favourable Neurologic Status at Discharge
Description
Favourable Neurologic Status at Discharge assessed using modified Rankin Score (MRS) < 3 at hospital discharge or 30 days after index arrest.
Time Frame
Discharge or 30 days after index arrest
Title
Survival to Discharge
Description
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.
Time Frame
Dicharge or 30 days after index arrest
Title
Clinical Instability at Discharge
Description
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.
Time Frame
Discharge or 30 days after index arrest
Title
Survival to 30 days after arrest
Description
Survival to 30 Days After Cardiac Arrest assessed as alive 30 days after the index cardiac arrest as confirmed by a brief telephone interview.
Time Frame
30 days after index arrest
Title
Accrual
Description
Accrual is the proportion of eligible subjects who have the study device applied
Time Frame
Through study completion, an average of 6 mos.
Other Pre-specified Outcome Measures:
Title
Device Failure
Description
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.
Time Frame
30 minutes from initiation of study intervention
Title
Expected Adverse Event Related to Device- Pain
Description
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.
Time Frame
Within 24 hours of Enrollment
Title
Expected Adverse Event Related to Device- Thrombophlebitis
Description
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.
Time Frame
Within 1 week of Enrollment
Title
Expected Adverse Event Related to Device- Sepsis
Description
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.
Time Frame
Within 1 week of Enrollment
Title
Expected Adverse Event Related to Cardiac Arrest
Description
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.
Time Frame
Discharge or 30 days after index arrest
Title
Unexpected Adverse Event
Description
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.
Time Frame
Discharge or 30 days after index arrest

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Graham Nichol, MD, MPH
Phone
206-521-1722
Email
ricstudy@uw.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Bartlett, MD
Phone
206 521 1722
Email
ricstudy@uw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Graham Nichol, MD, MPH
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emilby S Bartlett, MD MS
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
Graham Nichol
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Graham Nichol, MD MPH
Phone
206-521-1722
Email
ricstudy@uw.edu
First Name & Middle Initial & Last Name & Degree
Emily S Bartlett, MD MS
Email
ricstudy@uw.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Available upon request, subject to mutual agreement

Learn more about this trial

Remote Ischemic Conditioning to Enhance Resuscitation (RICE) Pilot

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