Therapeutic Hypothermia After Cardiac Arrest in Non Shockable Rhythm (HYPERION)

Therapeutic Hypothermia After Cardiac Arrest in Non Shockable Rhythm at Rescue Arrival: The HYPERION Study

Cardiac arrest is at present a major cause of mortality as well as a cause of disability for the surviving victims.In Europe, every year counts as 300,000 cardiac arrests responsible for 250,000 deaths. Thus, less than 20 % of patients discharged home with impaired quality of life associated with symptoms of tiredness, stress, anxiety. The prognosis is related to the initial cardiac rhythm present during the initiation of resuscitation. Recent progress in the improvement of mortality and neurological outcome has been achieved over the last decade thanks to the systematic implementation of a period of targeted temperature control between 32 and 34 ° C in patients who benefited from the realization of at least one electrical external shock.

There are theoretical and clinical arguments to think that achieving the same way a period of targeted temperature control between 32 and 34 ° C in patients treated for cardiac arrest with a non- shockable rhythm on arrival can also benefit from this procedure. However other arguments are against this hypothesis including an increase in the risk of infection , worsening of the patient's hemodynamic status with no benefit to him. To answer this question, we conduce a randomized multicenter study testing the potential improvement of neurological outcome through this procedure targeted temperature control between 32.5 and 33.5 ° C in these patients.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest
• Intervention / Treatment: Procedure: Targeted controlled temperature between 32.5 and 33.5°C; Procedure: Targeted controlled temperature between 36.5 and 37.5°C

• Study Type: Interventional
• Enrollment (Actual): 584
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Medical Intensive Care Unit
  • Angouleme, France
    • Medical Surgical Intensive Care Unit
  • Annecy, France, 74374
    • Medical Intensive Care Unit
  • Argenteuil, France
    • Medical Surgical Intensive Care Unit
  • Clermont-Ferrand, France, 63003
    • Medical Intensive Care Unit
  • Dijon, France
    • Medical Intensive Care Unit
  • La Roche Sur Yon, France
    • Medical Surgical Intensive Care Unit
  • Le Mans, France
    • Medical Surgical Intensive Care Unit
  • Lens, France
    • Medical Surgical Intensive Care Unit
  • Lille, France, 59037
    • Medical Intensive Care Unit
  • Limoges, France
    • Medical Surgical Intensive Care Unit
  • Lorient, France, 56322
    • Medical Surgical Intensive Care Unit
  • Montauban, France
    • Medical Surgical Intensive Care Unit
  • Nantes, France
    • Medical Intensive Care Unit
  • Orleans, France
    • Medical Intensive Care Unit
  • Paris, France
    • Cochin University Hospital Center
  • Poitiers, France
    • Medical Intensive Care Unit
  • Roanne, France, 42300
    • Medical Surgical Intensive Care Unit
  • Rodez, France, 12000
    • Medical Surgical Intensive Care Unit
  • Saint Brieuc, France
    • Medical Surgical Intensive Care Unit
  • Saint Malo, France, 35400
    • Medical Surgical Intensive Care Unit
  • Saint Nazaire, France
    • Medical Surgical Intensive Care Unit
  • Strasbourg, France
    • Medical Intensive Care Unit
  • Tours, France
    • Medical Intensive Care Unit
  • Versailles, France
    • Medical Surgical Intensive Care Unit
• Guadeloupe
  • Pointe-à-Pitre, Guadeloupe, 97120
    • CHU Pointe à pitre

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:

• Cardiac arrest in non shockable rhythm
• Glasgow score ≤ 8

Exclusion Criteria:

• No flow > 10 min
• Low flow > 60 min
• Major hemodynamic instability
• Delay between cardiac arrest and inclusion > 300 min
• Cirrhosis Child C
• Age < 18 years
• Pregnant women
• Patient with no liberty
• Lack of informed consent
• Prior inclusion in a research protocol involving cardiac arrest with draw, and whose primary endpoint focuses on the evaluation of a neurological score Day 90

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Targeted controlled temperature between 32.5 and 33.5°C; Patients will be placed in targeted temperature control between 32.5 and 33.5 ° C for 24 hours and then slowly rewarmed for targeted temperature control between 36.5 and 37.5 ° C for 24 hours.	Procedure: Targeted controlled temperature between 32.5 and 33.5°C; Therapeutic hypothermia ie targeted controlled temperature between 32.5° and 33.5°C will be induced in the active group. Usual method of controlled temperature will be use in ICU: internal active method or external active method.; Other Names: Therapeutic hypothermia; Induce hypothermia; Procedure: Targeted controlled temperature between 36.5 and 37.5°C; Temperature was maintain between 36.5° and 37.5°C in the control group. In case of temperature superior to 37.5°C or inferior to 36.5°C, a pharmaceutical treatment and/or active cooling or warming was introduce to maintain temperature between the range of 36.5 - 37.5°C.; Other Names: Normothermia
Placebo Comparator: Targeted controlled temperature between 36.5 and 37.5°C; Patients will be placed in targeted temperature control between 36.5 and 37.5 ° C for 48 hours.	Procedure: Targeted controlled temperature between 36.5 and 37.5°C; Temperature was maintain between 36.5° and 37.5°C in the control group. In case of temperature superior to 37.5°C or inferior to 36.5°C, a pharmaceutical treatment and/or active cooling or warming was introduce to maintain temperature between the range of 36.5 - 37.5°C.; Other Names: Normothermia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Neurological outcome assessed with Cerebral Performance Category scale	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at day 90		Day 90
Intensive Care Unit Mortality	Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days.	Discharge from Intensive Care Unit, an expected average of 7 days
Hospital Mortality	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks	Discharge from hospital, an expected average of 2 weeks
Quality of life Score	Quality of life at day 90 will be assessed by 36-Items Short Form for Health Survey telephonic interview	Day 90
Life autonomy	Life autonomy will be assessed by Index Activity of Daily Living, modified Barthel index, and by two normative question about life autonomy	Day 90
Neurocognitive evaluation	Neurocognitive status will be assessed by telephonic validated version of Mini Mental State Examination	Day 90
Post traumatic stress disorders symptoms	Post traumatic stress disorders symptoms will be assessed by Impact Event Scale Revised	Day 90
Intensive Care Unit length of stay	Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days	Discharge from Intensive Care Unit, an expected average of 7 days
Hospital length of stay	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.	Discharge from hospital, an expected average of 2 weeks
Mechanical ventilation duration	Participants will be followed for the duration of mechanical ventilation, an expected average of 4 days	Time from extubation, an expected average of 4 days
Severe hemorrhage	Severe hemorrhage is define by transfusion of 1 or more blood product requirement and/or intracranial hemorrhage. Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.	Intensive care unit length of stay, an expected average of 7 days
Nosocomial Bloodstream infection	Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.	Intensive care unit length of stay, an expected average of 7 days
Early onset pneumonia		2 days
Ventilated Associated Pneumonia	Participants will be followed for the duration of mechanical ventilation, an expected average of 4 days	Duration of mechanical ventilation, an expected average of 4 days
Central Veinous Catheter infection	Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.	Intensive care unit length of stay, an expected average of 7 days
Total dose of inotropic drugs	Total dose of different inotropic drugs (Epinephrine, Norepinephrine, Dobutamine) will be compare between 2 groups during targetted controlled temperature management period.	48 hours
Extra renal support requirement	Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days	Intensive care unit length of stay, an expected 7 days
Acute pulmonary oedema by left ventricular failure	Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days.	Intensive care length of stay, an expected 7 days
Seizure	Participants will be followed for the duration of Intensive care unit stay, an expected average of 7 days	Intensive care length of stay, an expected 7 days
Severe arrythmia	Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment. Participants will be followed for the duration of Intensive Care Unit stay, an expected average of 7 days.	Intensive care unit length of stay, an expected 7 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Departemental Vendee
• Collaborators: University Hospital, Tours

Publications and helpful links

General Publications

• Ziriat I, Le Thuaut A, Colin G, Merdji H, Grillet G, Girardie P, Souweine B, Dequin PF, Boulain T, Frat JP, Asfar P, Francois B, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Massart N, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Reignier J, Cariou A, Lascarrou JB. Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data. Ann Intensive Care. 2022 Oct 17;12(1):96. doi: 10.1186/s13613-022-01071-z.
• Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J; CRICS-TRIGGERSEP Group. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med. 2019 Dec 12;381(24):2327-2337. doi: 10.1056/NEJMoa1906661. Epub 2019 Oct 2.
• Lascarrou JB, Meziani F, Le Gouge A, Boulain T, Bousser J, Belliard G, Asfar P, Frat JP, Dequin PF, Gouello JP, Delahaye A, Hssain AA, Chakarian JC, Pichon N, Desachy A, Bellec F, Thevenin D, Quenot JP, Sirodot M, Labadie F, Plantefeve G, Vivier D, Girardie P, Giraudeau B, Reignier J; Clinical Research in Intensive Care and Sepsis (CRICS) Group and HYPERION Study Group. Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial. Scand J Trauma Resusc Emerg Med. 2015 Mar 7;23:26. doi: 10.1186/s13049-015-0103-5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2014
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Cardiac arrest; Therapeutic hypothermia; successful resuscitation; Targeted controlled temperature; Non shockable rhythm
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia
• Other Study ID Numbers: RCB 2012-A00405-38