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Completed

NCT Number: NCT02035839

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

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.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Charité - Universitätsmedizin Berlin, Berlin, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Target Temperature Management of 34°C

Device

In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.

Target Temperature Management of 32°C

Device

In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.

Target Temperature Management of 33°C

Device

In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.

Primary outcomes

  1. Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest.

    Time frame: at 90 days after out-of-hospital cardiac arrest

Secondary outcomes

  1. 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)

    Time frame: 24 hours

  2. Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia

    Time frame: 24 hours

  3. Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia

    Time frame: 26 hours

  4. Treatment Success: 4. rate of cooling in °C per hour

    Time frame: Per hour

  5. Treatment Success: 5. rate of rewarming in °C per hour

    Time frame: Per hour

  6. Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion

    Time frame: 90 days

  7. Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)

    Time frame: 90 days

  8. Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion

    Time frame: 90 days

  9. Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)

    Time frame: 90 days

  10. Outcomes: 5. Survival at 90 days measured as proportion

    Time frame: 90 days

  11. Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)

    Time frame: 90 days

  12. Outcomes: 7. ICU-free survival within 90 days measured in days

    Time frame: 90 days

  13. Outcomes: 8. Hospital-free survival within 90 days measured in days

    Time frame: 90 days

  14. Outcomes: 9. Adverse events a. Device related b. Procedure related

    Time frame: 90 days

  15. Subgroup analysis

    Time frame: 1 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.

  16. Subgroups of Special Interest Age of Patients

    Time frame: Duration of the trial

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

  17. Timings of initiation of hypothermia

    Time frame: <4 hours of restoration of spontaneous circulation; or > 4 hours

    (ii) > 65 years.

  18. Patient Gender

    Time frame: Male or Female

    Subgroups to assess Consistency of Effect

  19. Observational status of arrest

    Time frame: Witnessed by EMS; Witnessed by bystanders

  20. Location of cardiac arrest

    Time frame: Public;Home; or Group residence (e.g. nursing home)

  21. Bystander CPR status:

    Time frame: Performed; or Not performed.

  22. AED status:

    Time frame: Applied by layperson;Applied by EMS provider;Not applied

  23. Response time interval from call to initiation of CPR by EMS, among witnessed arrests:

    Time frame: < 10 minutes;> 10 minutes.

Sponsors and collaborators

Lead sponsor

ZOLL Circulation, Inc., USA

Industry

Collaborators

  • Instituto de Investigación Hospital Universitario La Paz

Registry information

Official study title

A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of Out-of-hospital Cardiac Arrest.

Acronym: FROST

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Jan 14, 2014
Registry last updated
Jun 26, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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