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

Primary Purpose

Out-Of-Hospital Cardiac Arrest

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Target Temperature Management of 34°C
Target Temperature Management of 32°C
Target Temperature Management of 33°C
Sponsored by
ZOLL Circulation, Inc., USA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Out-Of-Hospital Cardiac Arrest focused on measuring Target Temperature Management, Cooling comatose survivors from OHCA, Good neurological outcome at modified Rankin Score (mRS) ≤ 3

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Charité - Universitätsmedizin Berlin
  • Hospital Universitario La Paz. Planta
  • H. Principe de Asturias
  • Germans Trias i Pujol University Hospital
  • Hospital de Sant Pau
  • Hospital Universitario de Bellvitge
  • Hospital Universitari de Girona Doctor Josep Trueta
  • Hospital General Universitario Gregorio Marañón.
  • Hospital San Carlos
  • Hospital Universitario de Salamanca
  • Hospital Universitario de Canarias
  • H. University of Santiago de Compostela
  • Hospital Universitarion Virgen de la Macarena
  • Hospital Universitario Araba Txagorritxu

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Target Temperature Management of 34°C

Target Temperature Management of 32°C

Target Temperature Management of 33°C

Arm Description

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

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

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

Outcomes

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.

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)
Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia
Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia
Treatment Success: 4. rate of cooling in °C per hour
Treatment Success: 5. rate of rewarming in °C per hour
Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion
Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)
Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion
Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)
Outcomes: 5. Survival at 90 days measured as proportion
Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)
Outcomes: 7. ICU-free survival within 90 days measured in days
Outcomes: 8. Hospital-free survival within 90 days measured in days
Outcomes: 9. Adverse events a. Device related b. Procedure related
Subgroup analysis
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
18 to 65 years; or (ii) > 65 years.
Timings of initiation of hypothermia
(ii) > 65 years.
Patient Gender
Subgroups to assess Consistency of Effect
Observational status of arrest
Location of cardiac arrest
Bystander CPR status:
AED status:
Response time interval from call to initiation of CPR by EMS, among witnessed arrests:

Full Information

First Posted
November 27, 2013
Last Updated
June 25, 2018
Sponsor
ZOLL Circulation, Inc., USA
Collaborators
Instituto de Investigación Hospital Universitario La Paz
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1. Study Identification

Unique Protocol Identification Number
NCT02035839
Brief Title
Finding the Optimal Cooling tempeRature After Out-of-HoSpiTal Cardiac Arrest
Acronym
FROST
Official Title
A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of Out-of-hospital Cardiac Arrest.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ZOLL Circulation, Inc., USA
Collaborators
Instituto de Investigación Hospital Universitario La Paz

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Out-Of-Hospital Cardiac Arrest
Keywords
Target Temperature Management, Cooling comatose survivors from OHCA, Good neurological outcome at modified Rankin Score (mRS) ≤ 3

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Target Temperature Management of 34°C
Arm Type
Other
Arm Description
In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Arm Title
Target Temperature Management of 32°C
Arm Type
Other
Arm Description
In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Arm Title
Target Temperature Management of 33°C
Arm Type
Other
Arm Description
In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.
Intervention Type
Device
Intervention Name(s)
Target Temperature Management of 34°C
Intervention Description
In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Intervention Type
Device
Intervention Name(s)
Target Temperature Management of 32°C
Intervention Description
In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Intervention Type
Device
Intervention Name(s)
Target Temperature Management of 33°C
Intervention Description
In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
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
Title
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
Title
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
Title
Treatment Success: 4. rate of cooling in °C per hour
Time Frame
Per hour
Title
Treatment Success: 5. rate of rewarming in °C per hour
Time Frame
Per hour
Title
Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion
Time Frame
90 days
Title
Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)
Time Frame
90 days
Title
Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion
Time Frame
90 days
Title
Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)
Time Frame
90 days
Title
Outcomes: 5. Survival at 90 days measured as proportion
Time Frame
90 days
Title
Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)
Time Frame
90 days
Title
Outcomes: 7. ICU-free survival within 90 days measured in days
Time Frame
90 days
Title
Outcomes: 8. Hospital-free survival within 90 days measured in days
Time Frame
90 days
Title
Outcomes: 9. Adverse events a. Device related b. Procedure related
Time Frame
90 days
Title
Subgroup analysis
Description
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.
Time Frame
1 year
Title
Subgroups of Special Interest Age of Patients
Description
18 to 65 years; or (ii) > 65 years.
Time Frame
Duration of the trial
Title
Timings of initiation of hypothermia
Description
(ii) > 65 years.
Time Frame
<4 hours of restoration of spontaneous circulation; or > 4 hours
Title
Patient Gender
Description
Subgroups to assess Consistency of Effect
Time Frame
Male or Female
Title
Observational status of arrest
Time Frame
Witnessed by EMS; Witnessed by bystanders
Title
Location of cardiac arrest
Time Frame
Public;Home; or Group residence (e.g. nursing home)
Title
Bystander CPR status:
Time Frame
Performed; or Not performed.
Title
AED status:
Time Frame
Applied by layperson;Applied by EMS provider;Not applied
Title
Response time interval from call to initiation of CPR by EMS, among witnessed arrests:
Time Frame
< 10 minutes;> 10 minutes.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. Esteban Lopez-de-Sa, M.D
Organizational Affiliation
Hospital Universitario La Paz. Planta
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Hospital Universitario La Paz. Planta
City
Madrid
State/Province
Pso. De La Castellana
ZIP/Postal Code
26128046
Country
Spain
Facility Name
H. Principe de Asturias
City
Alcala de Henares
Country
Spain
Facility Name
Germans Trias i Pujol University Hospital
City
Badalona
Country
Spain
Facility Name
Hospital de Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Bellvitge
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Girona
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañón.
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
88-182, 37007
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
Santa Cruz de Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
H. University of Santiago de Compostela
City
Santiago de Compostela
Country
Spain
Facility Name
Hospital Universitarion Virgen de la Macarena
City
Sevilla
Country
Spain
Facility Name
Hospital Universitario Araba Txagorritxu
City
Vitoria
ZIP/Postal Code
01009
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30343315
Citation
Lopez-de-Sa E, Juarez M, Armada E, Sanchez-Salado JC, Sanchez PL, Loma-Osorio P, Sionis A, Monedero MC, Martinez-Selles M, Martin-Benitez JC, Ariza A, Uribarri A, Garcia-Acuna JM, Villa P, Perez PJ, Storm C, Dee A, Lopez-Sendon JL. A multicentre randomized pilot trial on the effectiveness of different levels of cooling in comatose survivors of out-of-hospital cardiac arrest: the FROST-I trial. Intensive Care Med. 2018 Nov;44(11):1807-1815. doi: 10.1007/s00134-018-5256-z. Epub 2018 Oct 21.
Results Reference
derived

Learn more about this trial

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

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