Early Coronary Angiography Versus Delayed Coronary Angiography (PEARL)

A Pilot Randomized Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography for Post-Cardiac Arrest Patients Without ECG ST Segment Elevation

This study is a pilot, multi-centered, randomized, clinical trial to evaluate the safety and efficacy of performing early Coronary Angiography (CAG) versus no early CAG in post-cardiac arrest patients without ST segment elevation. Safety will be assessed by evaluating the association of major adverse events (re-arrest, bleeding, pulmonary edema, hypotension, acute renal insufficiency, and pneumonia) with early coronary angiogram. Efficacy will be assessed by a composite endpoint of improved left ventricular regional and global function (both regional wall motion analysis and left ventricular ejection fraction) as measured by echocardiography prior to hospital discharge and favourable neurological function (Cerebral Performance Categories 1 or 2) at discharge.

Study Overview

• Status: Terminated
• Conditions: Cardiac Arrest; Hypothermia; Out-of-Hospital Cardiac Arrest
• Intervention / Treatment: Procedure: Early Angiography

Detailed Description

Cardiac arrest is a major public health issue. Arizona has been a leader in improving long-term survival by introducing new and innovative resuscitation approaches including "Chest Compression-Only CPR" and "Cardiocerebral Resuscitation". Post-resuscitation care is the next great opportunity for further improvements. Early coronary angiography (CAG) combined with therapeutic hypothermia has become the recommended standard of care for post-cardiac arrest patients manifesting ST segment elevation on their electrocardiogram (ECG). However, the majority of cardiac arrest victims do not have ST segment elevation. There is clinical equipoise as to whether these patients will benefit from early CAG.

Subjects who are qualified for the study will be randomized 1:1 to one of two groups.

° Intervention Group-Early coronary angiography (door-to-angiography) within 120 minutes of admission to Emergency Department.

or

° Control Group-No early coronary angiography (within the first six hours from admission)

All enrolled patients, will be treated with therapeutic hypothermia which is standard of care, beginning simultaneously with both groups or within at least 2 hours of hospital arrival.

Subject will be followed for 180 days for safety and long-term survival.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Center Ljubljana
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Center-Tucson Campus
    • Tucson, Arizona, United States, 85724
      • Banner University Medical Center-South Campus
  • Maine
    • Portland, Maine, United States, 04103
      • Tufts University School of Medicine, Maine Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cardiovascular Research Unit

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

Inclusion Criteria:

1. All successfully resuscitated out-of-hospital cardiac arrest patients with a suspected cardiac etiology for their non-traumatic arrest
2. Age greater than 18 years
3. The post resuscitation ECG shows no evidence of ST segment elevation

Exclusion Criteria:

1. Non-resuscitated (no sustained pulse and BP)
2. Presence ST segment elevation or new left bundle branch block present on the post-resuscitation ECG
3. Suspected non-cardiac etiology for their arrest such as respiratory failure, asphyxia, pulmonary embolus, shock, trauma, drug overdose, or CNS bleed as likely cause of the cardiac arrest
4. Known "Do Not Resuscitate" status
5. Minors (<18 years old)
6. Prisoners
7. Significant bleeding or blunt trauma
8. Known or confirmed pregnancy test by urinalysis
9. Patients who are known to have received any other investigational therapies within the 30 days prior to enrollment or during study duration will be excluded unless these studies have been reviewed and approved by the Study Steering Committee.
10. Known "opt out" choice; wearing Opt-out band for any EFIC approved study or on an "Opt-out" list

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; Early Angiography with purpose of coronary revascularization within 120 minutes of admission to ED, post out-of-hospital cardiac arrest, suspicious for cardiac etiology and no ST segment elevation on ECG	Procedure: Early Angiography; Coronary Angiography within 120 minutes of admission for out-of-hospital cardiac arrest with ROSC
No Intervention: Control Group; Standard of care treatment including therapeutic hypothermia in subjects post resuscitation, out-of-hospital cardiac arrest, suspicious for cardiac etiology and no ST segment elevation on ECG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Efficacy of early coronary angiography in the out-of-hospital cardiac arrest (OHCA) patient population.	Safety will be assessed by evaluating any association of major adverse events (re-arrest, bleeding, pulmonary edema, hypotension, acute renal insufficiency, and pneumonia) with early coronary angiography.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival from hospital at: 30 days post discharge and 180 days post discharge	Composite endpoint of improved left ventricular regional and global function (both regional wall motion analysis and left ventricular ejection fraction) as measured by echocardiography prior to hospital discharge, survival to discharge and favourable. Left ventricular regional function and left ventricular ejection fraction as measured by echocardiography will be measured prior to discharge or up to 180 days post hospital discharge.	30 days and 180 days
Cognitive functional status	As measured by Modified Rankin Score (mRS) and Cerebral Performance Category (CPC) at multiple points up to 180 days post hospital discharge	180 days
Neurocognitive Testing	Neurocognitive function will be assessed at various time points utilizing a variety of tests from ICU discharge to 180 days post hospital discharge such as MMSE, MOCA, HADS, and IQCODE	180 days

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: Mayo Clinic; The Alfred; University Medical Centre Ljubljana; MaineHealth
• Investigators: Principal Investigator: Karl B Kern, MD, University of Arizona

Publications and helpful links

General Publications

• Kern KB, Radsel P, Jentzer JC, Seder DB, Lee KS, Lotun K, Janardhanan R, Stub D, Hsu CH, Noc M. Randomized Pilot Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography After Cardiac Arrest Without ST-Segment Elevation: The PEARL Study. Circulation. 2020 Nov 24;142(21):2002-2012. doi: 10.1161/CIRCULATIONAHA.120.049569. Epub 2020 Sep 28. Erratum In: Circulation. 2020 Nov 24;142(21):e374.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: February 26, 2015
• First Submitted That Met QC Criteria: March 12, 2015
• First Posted (Estimate): March 13, 2015

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: December 29, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia; Out-of-Hospital Cardiac Arrest
• Other Study ID Numbers: NCT02387398

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES