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Finding the Optimal Cooling tempeRature After Out-of-HoSpiTal Cardiac Arrest

Not Applicable
Completed
Conditions
Out-Of-Hospital Cardiac Arrest
Interventions
Device: Target Temperature Management of 32°C
Device: Target Temperature Management of 33°C
Device: Target Temperature Management of 34°C
Registration Number
NCT02035839
Lead Sponsor
ZOLL Circulation, Inc., USA
Brief Summary

To assess the fraction of subjects surviving with good neurological outcome at 90 days for 3 different levels of hypothermia, in comatose survivors from out-of-hospital cardiac arrest.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
Inclusion Criteria
  • Signed informed consent (obtained from their legal representative)
  • 18 years of age or older and less than 80 years old.
  • Witnessed OHCA of presumed cardiac cause
  • Sustained ROSC (when chest compressions have not been required for 20 consecutive minutes and signs of circulation persist)
  • Initial shockable cardiac rhythm (documented by ECG or AED)
  • Interval from collapse to advance life support < 20 minutes
  • Interval from collapse to ROSC < 60 minutes
  • Lack of meaningful response to verbal commands upon arrival to hospital after suffering non-traumatic cardiac arrest in an out-of-hospital setting
  • Systolic blood pressure of >90 maintained for a least 30 minutes post-ROSC without pressors, or with a stable dose of pressors
Exclusion Criteria
  • Traumatic cardiac arrest
  • Toxicological etiology
  • Known or suspected pregnancy
  • Do Not Attempt to Resuscitate order in force
  • Unwitnessed arrest
  • In-Hospital arrest
  • Anatomy, previous surgery or disease state contraindicating femoral venous access
  • Received neuromuscular blocking agents prior to assessing level of consciousness following ROSC
  • Neurological evaluation insufficient/incomplete after ROSC but prior to randomization.
  • Body core temperature < 34ºC at randomization
  • Current Inferior Vena Cava (IVC) filter
  • Known history of acute neurological illness or severe functional disabilities prior to arrest (e.g., seizures, traumatic brain injury, increased intracranial pressures, intra-cerebral hemorrhage, etc).
  • Known hypersensitivity to hypothermia including a history of Raynaud's disease
  • Suspected or confirmed acute intracranial bleeding
  • Suspected or confirmed acute stroke
  • Terminal illness or life expectancy of less than 3 months prior to arrest
  • Currently enrolled in another investigational new drug or device trial that has not completed the primary endpoint or that clinically interferes with this Trial's endpoints (For the purpose of this protocol, subjects involved in extended follow-up trials or registries for products that are currently commercially available are not considered enrolled in an investigational trial).
  • Transferred from a non-participating hospital.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Target Temperature Management of 32°CTarget Temperature Management of 32°CIn hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Target Temperature Management of 33°CTarget Temperature Management of 33°CIn hospital target temperature management to achieve core body temperature of 33°C for 24 hours.
Target Temperature Management of 34°CTarget Temperature Management of 34°CIn hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Primary Outcome Measures
NameTimeMethod
Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest.at 90 days after out-of-hospital cardiac arrest
Secondary Outcome Measures
NameTimeMethod
Location of cardiac arrestPublic;Home; or Group residence (e.g. nursing home)
Bystander CPR status:Performed; or Not performed.
AED status:Applied by layperson;Applied by EMS provider;Not applied
Treatment Success: 1. proportion of subjects that can be therapeutically cooled to randomly allocated target temperature ±0.3°C (as measured by the temperature probe)24 hours
Treatment Success: 4. rate of cooling in °C per hourPer hour
Outcomes: 5. Survival at 90 days measured as proportion90 days
Outcomes: 7. ICU-free survival within 90 days measured in days90 days
Outcomes: 9. Adverse events a. Device related b. Procedure related90 days
Subgroup analysis1 year

A priori plan to assess heterogeneity of effect among specific subgroups of special interest as well as to assess the consistency of treatment effect among different subpopulations defined by each of multiple baseline characteristics of the patients. These will be assessed by repeating the primary analysis in the subgroups defined below, using interaction terms.

Timings of initiation of hypothermia<4 hours of restoration of spontaneous circulation; or > 4 hours

(ii) \> 65 years.

Patient GenderMale or Female

Subgroups to assess Consistency of Effect

Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia26 hours
Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)90 days
Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)90 days
Response time interval from call to initiation of CPR by EMS, among witnessed arrests:< 10 minutes;> 10 minutes.
Observational status of arrestWitnessed by EMS; Witnessed by bystanders
Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion90 days
Outcomes: 8. Hospital-free survival within 90 days measured in days90 days
Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia24 hours
Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion90 days
Treatment Success: 5. rate of rewarming in °C per hourPer hour
Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)90 days
Subgroups of Special Interest Age of PatientsDuration of the trial

18 to 65 years; or (ii) \> 65 years.

Trial Locations

Locations (14)

The Charité - Universitätsmedizin Berlin

🇩🇪

Berlin, Germany

Germans Trias i Pujol University Hospital

🇪🇸

Badalona, Spain

Hospital Universitario La Paz. Planta

🇪🇸

Madrid, Pso. De La Castellana, Spain

H. Principe de Asturias

🇪🇸

Alcala de Henares, Spain

Hospital de Sant Pau

🇪🇸

Barcelona, Spain

Hospital Universitario de Bellvitge

🇪🇸

Barcelona, Spain

Hospital Universitari de Girona Doctor Josep Trueta

🇪🇸

Girona, Spain

Hospital San Carlos

🇪🇸

Madrid, Spain

Hospital Universitario de Salamanca

🇪🇸

Salamanca, Spain

Hospital Universitario de Canarias

🇪🇸

Santa Cruz de Tenerife, Spain

H. University of Santiago de Compostela

🇪🇸

Santiago de Compostela, Spain

Hospital Universitarion Virgen de la Macarena

🇪🇸

Sevilla, Spain

Hospital General Universitario Gregorio Marañón.

🇪🇸

Madrid, Spain

Hospital Universitario Araba Txagorritxu

🇪🇸

Vitoria, Spain

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