Study of Survivors of Different Types of Cardiac Arrest and Their Neurological Recovery

• ClinicalTrials.gov Identifier: NCT02033720
• Recruitment Status: Unknown
• First Posted: January 13, 2014
• Last Update Posted: January 13, 2014
• Sponsor: Lawson Health Research Institute
• Collaborator: University of Western Ontario, Canada
• Information provided by (Responsible Party): Eyad AlThenayan, University of Western Ontario, Canada

Study Description

Brief Summary:

After successful resuscitation from certain types of cardiac arrest, total body cooling is now a well established treatment that improves the chances of the brain recovering. This however, has only been definitively proven after a certain type of cardiac arrest that is "ventricular fibrillation / ventricular tachycardia". The purpose of this study is to explore if total body cooling is beneficial for patients recovering from another type of cardiac arrest that is "pulseless electrical activity".

HYPOTHESIS:

Patients undergoing post-cardiac arrest therapeutic hypothermia have better neurological outcomes if their initial arrest rhythm is pulseless electrical activity (PEA) in comparison to asystole.

Condition or disease	Intervention/treatment
Postcardiac Arrest; Pulseless Electrical Activity; Asystole	Other: No treatment; Other: Therapeutic hypothermia

Detailed Description:

STUDY RATIONALE AND BACKGROUND INFORMATION:

After successful resuscitation from cardiac arrest the body experiences a period of global reperfusion. During this period, patients may show signs of myocardial stunning, lactic acidosis, neurological injury and reperfusion syndrome. This constellation of findings constitutes what is known as post-cardiac arrest syndrome. The brain appears to be one of the most vulnerable organs to injury during this reperfusion phase and varying degrees of cognitive impairment may be the end result. Inducing mild therapeutic hypothermia has been shown to be protective for the brain in this setting and has been demonstrated to improve neurological recovery. The evidence for this however, is only conclusive in cases where the arrest is in a shockable rhythm i.e. pulseless ventricular tachycardia and ventricular fibrillation.

In 2002, two randomized controlled trials were published showing an improvement in neurological outcomes in patients treated with mild therapeutic hypothermia post resuscitation from shockable cardiac arrest. Therapeutic hypothermia has since been widely adopted by most authorities as part of the comprehensive treatment bundle for post cardiac arrest syndrome. Whether there is any benefit for patients arrested in non-shockable rhythms however, is a matter of controversy. Some have reported improved mortality and better neurological outcomes with therapeutic hypothermia in this patient population. Others have reported no benefit or even a trend towards harm. And although the matter remains controversial, the recommendation still stands for therapeutic hypothermia to be offered for all comatose survivors of cardiac arrest whatever the arrest rhythm.

Most previous reports have examined the differences between shockable and non-shockable rhythms in terms of neurological outcome and mortality rates after therapeutic hypothermia. To our knowledge, no study has examined the differences in outcome between the two types of non-shockable rhythms, that is pulseless electrical activity (PEA) and asystole. We hypothesize that during PEA arrests, patients may retain some degree of cerebral perfusion and hence have better neurological outcomes post-resuscitation. That is in contrast to asystole where patients are likely to have no cerebral perfusion. In this study we attempt to detect any possible differences in neurological recovery (as indicated by the Cerebral Performance Category scale on hospital discharge) after therapeutic hypothermia, between patients arrested in PEA arrest and those arrested in asystole.

Study Design

• Study Type: Observational
• Estimated Enrollment: 400 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Neurological Outcomes After Cardiac Arrest in Pulseless Electrical Activity in Comparison to Asystole. Are All Non-shockable Rhythms the Same?
• Study Start Date: January 2014
• Estimated Primary Completion Date: December 2014
• Estimated Study Completion Date: February 2015

Groups and Cohorts

Group/Cohort	Intervention/treatment
Shockable arrest; Initial arrest rhythm shockable. This is either pulseless ventricular tachycardia (pulseless VT) or ventricular fibrillation (VF).	Other: No treatment; No therapeutic hypothermia was induced.; Other Names: No therapeutic hypothermia.; Control.; Other: Therapeutic hypothermia; Hypothermia was induced after successful resuscitation from cardiac arrest.; Other Names: Hypothermia; Induced hypothermia; Mild therapeutic hypothermia; Cooling; Targeted temperature management
Pulseless electrical activity; Initial arrest rhythm is pulseless electrical activity.	Other: No treatment; No therapeutic hypothermia was induced.; Other Names: No therapeutic hypothermia.; Control.; Other: Therapeutic hypothermia; Hypothermia was induced after successful resuscitation from cardiac arrest.; Other Names: Hypothermia; Induced hypothermia; Mild therapeutic hypothermia; Cooling; Targeted temperature management
Asystole; Initial arrest rhythm is asystole.	Other: No treatment; No therapeutic hypothermia was induced.; Other Names: No therapeutic hypothermia.; Control.; Other: Therapeutic hypothermia; Hypothermia was induced after successful resuscitation from cardiac arrest.; Other Names: Hypothermia; Induced hypothermia; Mild therapeutic hypothermia; Cooling; Targeted temperature management

Outcome Measures

Primary Outcome Measures :

1. Cerebral performance category score on hospital discharge [ Time Frame: Upon discharge from hospital, assessed up to 36 months postcardiac arrest ]

   Neurological outcome on discharge from hospital as defined by the cerebral performance category (CPC) scale. The CPC scale is a 5 point scale. The outcome measure will be dichotomized into good or bad. Good outcome will be equivalent to CPC scores of 1 & 2 (where the patient is independent), and bad outcome will be equivalent to CPC scores of 3, 4 & 5 (where the patient is either dependent or dead).

   CPC Scale:

   1. Functioning normally and independent, possibly with a minor disability.
   2. Moderately disabled, still independent.
   3. Conscious but with a severe disability, dependent.
   4. Unconscious (comatose or in a persistent vegetative state).
   5. Brain dead or dead by traditional criteria.

Secondary Outcome Measures :

1. Hospital length of stay postcardiac arrest [ Time Frame: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest ]
   Hospital length of stay (LOS) post-cardiac arrest will be calculated from the day of the cardiac arrest to the day of hospital discharge. If prior to the arrest the patient was an inpatient, we will only count the days from the arrest to discharge. Days spent in hospital prior to the arrest will not be included.
2. Intensive care unit length of stay postcardiac arrest [ Time Frame: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest ]
   The length of stay (LOS) in the intensive care unit (ICU) in days, after successful resuscitation from cardiac arrest.
3. Neurological status after hospital discharge [ Time Frame: Assessed up to 12 months from hospital discharge ]
   Neurological status as documented on the patient's first outpatient clinic visit, assessed up to 12 months from hospital discharge. This will be analyzed as a secondary outcome only if enough data is generated on chart review.

Other Outcome Measures:

1. Time to obeying commands [ Time Frame: Assessed up to 21 days postcardiac arrest ]
   Total time in days from the cardiac arrest until the patient is able to obey commands, as documented in the patient's chart.
2. Documented negative neurological prognosticators [ Time Frame: Upon withdrawal of life support, assessed up to 3 months postcardiac arrest ]

   For patient's in which the reason for withdrawal of life support is poor neurological outcome, the number of negative neurological prognosticators recorded in the chart will be examined.

   Examples of negative prognosticators include: negative somatosensory evoked potentials on post arrest day 3, post arrest status epilepticus, absent brain stem reflexes beyond post arrest day 2... etc.

3. Post arrest neurological investigations (including imaging studies) [ Time Frame: Performed within 21 days from cardiac arrest ]
   All neurological investigations done within 21 days from cardiac arrest will be examined including electroencephalograms, somatosensory evoked potentials, brain magnetic resonance imaging, brain computerized tomography (CT) scans... etc.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

All patients admitted to the intensive care unit (ICU) with a diagnosis of postcardiac arrest between Jan 2008 and Dec 2012 will be examined.

Criteria

Inclusion Criteria:

• Admission to adult ICU (age ≥18 years) at London Health Sciences Centre
• Primary reason for ICU admission: postcardiac arrest
• Both in-hospital and out-of-hospital cardiac arrest will be included
• ICU admission between Jan 2008 and Dec 2012.

Exclusion Criteria:

- ICU admissions primarily for reasons other than cardiac arrest.

Contacts and Locations

Contacts

Contact: Ahmed F Hegazy, MD, FRCPC; 1(519) 860-4917; ahmed.hegazy@londonhospitals.ca

Contact: Eyad AlThenayan, MD; Eyad.Althenayan@lhsc.on.ca

Locations

Canada, Ontario

University Hospital, London Health Sciences Centre, University of Western Ontario; Not yet recruiting

London, Ontario, Canada, N6A 5A5

Contact: Ahmed F Hegazy, MD, FRCPC 1(519) 860-4917 ahmed.hegazy@londonhospitals.ca

Contact: Eyad Althenayan, MD 1 (519) 685-8500 ext 19119 eyad.althenayan@lhsc.on.ca

Sub-Investigator: Ahmed F Hegazy, MD, FRCPC

Victoria Hospital, London Health Sciences Centre, University of Western Ontario; Not yet recruiting

London, Ontario, Canada, N6A 5W9

Contact: Ahmed F Hegazy, MD, FRCPC 1(519) 860-4917 ahmed.hegazy@londonhospitals.ca

Contact: Eyad Althenayan, MD 1 (519) 685-8500 ext 19119 eyad.althenayan@lhsc.on.ca

Sub-Investigator: Ahmed F Hegazy, MD, FRCPC

Sponsors and Collaborators

Lawson Health Research Institute

University of Western Ontario, Canada

Investigators

• Principal Investigator: Eyad Althenayan, MD; University of Western Ontario, Canada
• Study Director: Philip Jones, MD, FRCPC; University of Western Ontario, Canada
• Study Chair: Bryan Young, MD, FRCPC; University of Western Ontario, Canada
• Study Director: Ahmed F Hegazy, MD, FRCPC; University of Western Ontario, Canada
• Study Director: Ana Igric, MD, FRCSC; University of Western Ontario, Canada
• Study Director: Carolyn Benson, MD; University of Western Ontario, Canada

More Information

Publications:

Holzer M. Targeted temperature management for comatose survivors of cardiac arrest. N Engl J Med. 2010 Sep 23;363(13):1256-64. doi: 10.1056/NEJMct1002402. Review.

Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63.

Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. Erratum in: N Engl J Med 2002 May 30;346(22):1756.

Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, Jacobs I, Kleinman ME, Kloeck W, Koster RW, Lim SH, Mancini ME, Montgomery WH, Morley PT, Morrison LJ, Nadkarni VM, O'Connor RE, Okada K, Perlman JM, Sayre MR, Shuster M, Soar J, Sunde K, Travers AH, Wyllie J, Zideman D. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010 Oct 19;122(16 Suppl 2):S250-75. doi: 10.1161/CIRCULATIONAHA.110.970897.

Arrich J; European Resuscitation Council Hypothermia After Cardiac Arrest Registry Study Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007 Apr;35(4):1041-7.

Testori C, Sterz F, Behringer W, Haugk M, Uray T, Zeiner A, Janata A, Arrich J, Holzer M, Losert H. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011 Sep;82(9):1162-7. doi: 10.1016/j.resuscitation.2011.05.022. Epub 2011 Jun 12.

Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pène F, Vivien B, Varenne O, Carli P, Jouven X, Empana JP, Cariou A. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011 Mar 1;123(8):877-86. doi: 10.1161/CIRCULATIONAHA.110.987347. Epub 2011 Feb 14.

• Responsible Party: Eyad AlThenayan, Dr. Eyad AlThenayan, University of Western Ontario, Canada
• ClinicalTrials.gov Identifier: NCT02033720 History of Changes
• Other Study ID Numbers: 104666
• First Posted: January 13, 2014
• Last Update Posted: January 13, 2014
• Last Verified: January 2014

Keywords provided by Eyad AlThenayan, University of Western Ontario, Canada:

postcardiac arrest; post cardiac arrest syndrome; post cardiac arrest hypothermia; pulseless electrical activity; asystole; therapeutic hypothermia; therapeutic hypothermia after cardiac arrest; therapeutic hypothermia neurologic outcome

Additional relevant MeSH terms:

Heart Arrest; Heart Diseases; Cardiovascular Diseases