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

This study has been completed.
Sponsor:
Collaborator:
Instituto de Investigación Hospital Universitario La Paz
Information provided by (Responsible Party):
ZOLL Circulation, Inc., USA
ClinicalTrials.gov Identifier:
NCT02035839
First received: November 27, 2013
Last updated: April 25, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention
Out-Of-Hospital Cardiac Arrest.
Device: Target Temperature Management of 34°C
Device: Target Temperature Management of 32°C
Device: Target Temperature Management of 33°C

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Official Title: A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of Out-of-hospital Cardiac Arrest.

Resource links provided by NLM:


Further study details as provided by ZOLL Circulation, Inc., USA:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Treatment Success: 4. rate of cooling in °C per hour [ Time Frame: Per hour ] [ Designated as safety issue: No ]
  • Treatment Success: 5. rate of rewarming in °C per hour [ Time Frame: Per hour ] [ Designated as safety issue: No ]
  • Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 5. Survival at 90 days measured as proportion [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 7. ICU-free survival within 90 days measured in days [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 8. Hospital-free survival within 90 days measured in days [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Outcomes: 9. Adverse events a. Device related b. Procedure related [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Subgroup analysis [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Subgroups of Special Interest Age of Patients [ Time Frame: Duration of the trial ] [ Designated as safety issue: No ]
    18 to 65 years; or (ii) > 65 years.

  • Timings of initiation of hypothermia [ Time Frame: <4 hours of restoration of spontaneous circulation; or > 4 hours ] [ Designated as safety issue: No ]
    (ii) > 65 years.

  • Patient Gender [ Time Frame: Male or Female ] [ Designated as safety issue: No ]
    Subgroups to assess Consistency of Effect

  • Observational status of arrest [ Time Frame: Witnessed by EMS; Witnessed by bystanders ] [ Designated as safety issue: No ]
  • Location of cardiac arrest [ Time Frame: Public;Home; or Group residence (e.g. nursing home) ] [ Designated as safety issue: No ]
  • Bystander CPR status: [ Time Frame: Performed; or Not performed. ] [ Designated as safety issue: No ]
  • AED status: [ Time Frame: Applied by layperson;Applied by EMS provider;Not applied ] [ Designated as safety issue: No ]
  • Response time interval from call to initiation of CPR by EMS, among witnessed arrests: [ Time Frame: < 10 minutes;> 10 minutes. ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: March 2014
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Target Temperature Management of 34°C
In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Device: Target Temperature Management of 34°C
In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Target Temperature Management of 32°C
In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Device: Target Temperature Management of 32°C
In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Target Temperature Management of 33°C
In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.
Device: Target Temperature Management of 33°C
In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02035839

Locations
Germany
The Charité - Universitätsmedizin Berlin
Berlin, Germany, 13353
Spain
Hospital Universitario La Paz. Planta
Madrid, Pso. de la castellana, Spain, 26128046
H. Principe de Asturias
Alcala de Henares, Spain
Germans Trias i Pujol University Hospital
Badalona, Spain
Hospital de Sant Pau
Barcelona, Spain
Hospital Universitario de Bellvitge
Barcelona, Spain
Hospital Universitari de Girona Doctor Josep Trueta
Girona, Spain
Hospital General Universitario Gregorio Marañón.
Madrid, Spain, 28007
Hospital San Carlos
Madrid, Spain
Hospital Universitario de Salamanca
Salamanca, Spain, 88-182, 37007
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain, 38320
H. University of Santiago de Compostela
Santiago de Compostela, Spain
Hospital Universitarion Virgen de la Macarena
Sevilla, Spain
Hospital Universitario Araba Txagorritxu
Vitoria, Spain, 01009
Sponsors and Collaborators
ZOLL Circulation, Inc., USA
Instituto de Investigación Hospital Universitario La Paz
Investigators
Principal Investigator: Prof. Esteban Lopez-de-Sa, M.D Hospital Universitario La Paz. Planta
  More Information

Additional Information:
Responsible Party: ZOLL Circulation, Inc., USA
ClinicalTrials.gov Identifier: NCT02035839     History of Changes
Other Study ID Numbers: FROST I-Pilot Trial 
Study First Received: November 27, 2013
Last Updated: April 25, 2016
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by ZOLL Circulation, Inc., USA:
Target Temperature Management
Cooling comatose survivors from OHCA
Good neurological outcome at modified Rankin Score (mRS) ≤ 3

Additional relevant MeSH terms:
Heart Arrest
Out-of-Hospital Cardiac Arrest
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on May 23, 2016