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

• ClinicalTrials.gov Identifier: NCT01994772
• Recruitment Status: Completed
• First Posted: November 26, 2013
• Last Update Posted: January 16, 2019
• Sponsor: Centre Hospitalier Departemental Vendee
• Collaborator: University Hospital, Tours
• Information provided by (Responsible Party): Centre Hospitalier Departemental Vendee

Tracking Information

• First Submitted Date: November 7, 2013
• First Posted Date: November 26, 2013
• Last Update Posted Date: January 16, 2019
• Actual Study Start Date: January 26, 2014
• Actual Primary Completion Date: April 9, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 21, 2013): Neurological outcome assessed with Cerebral Performance Category scale [ Time Frame: Day 90 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2019)

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

Original Secondary Outcome Measures (submitted: November 21, 2013)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cardiac Arrest

Intervention

• 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 Name: Normothermia

Study Arms

• 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.
  Interventions:

  • Procedure: Targeted controlled temperature between 32.5 and 33.5°C
  • Procedure: Targeted controlled temperature between 36.5 and 37.5°C
• 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.
  Intervention: Procedure: Targeted controlled temperature between 36.5 and 37.5°C

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 21, 2013): 584
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 9, 2018
• Actual Primary Completion Date: April 9, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Guadeloupe

Administrative Information

• NCT Number: NCT01994772
• Other Study ID Numbers: RCB 2012-A00405-38
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Centre Hospitalier Departemental Vendee
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre Hospitalier Departemental Vendee
• Original Study Sponsor: Same as current
• Collaborators: University Hospital, Tours

Investigators

• Study Chair: Jean Baptiste Lascarrou, MD; CHU Nantes

• PRS Account: Centre Hospitalier Departemental Vendee
• Verification Date: January 2019