Out-Of-Hospital Cardiac ArrestFROSTNCT02035839
Finding the Optimal Cooling tempeRature After Out-of-HoSpiTal Cardiac Arrest
A study testing Target Temperature Management of 34°C, Target Temperature Management of 32°C and Target Temperature Management of 33°C in people with Out-Of-Hospital Cardiac Arrest, run by ZOLL Circulation, Inc., USA at 14 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Out-Of-Hospital Cardiac Arrest
- What is being tested?
- Target Temperature Management of 34°C, Target Temperature Management of 32°C and Target Temperature Management of 33°C
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Mar 2014to Apr 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- Traumatic cardiac arrest
- Toxicological etiology
- Known or suspected pregnancy
- Do Not Attempt to Resuscitate order in force
- Unwitnessed arrest
- In-Hospital arrest
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- 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.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
Spain13 sites
H. Principe de Asturias
Alcalá de Henares
Germans Trias i Pujol University Hospital
Badalona
Hospital de Sant Pau
Barcelona
Hospital Universitario de Bellvitge
Barcelona
Hospital Universitari de Girona Doctor Josep Trueta
Girona
Hospital Universitario La Paz. Planta
Madrid, Pso. de La Castellana, 26128046
Hospital General Universitario Gregorio Marañón.
Madrid, 28007
Hospital San Carlos
Madrid
Hospital Universitario de Salamanca
Salamanca, 88-182, 37007
Hospital Universitario de Canarias
Santa Cruz de Tenerife, 38320
H. University of Santiago de Compostela
Santiago de Compostela
Hospital Universitarion Virgen de la Macarena
Seville
Hospital Universitario Araba Txagorritxu
Vitoria-Gasteiz, 01009
About this study
Official title: A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of 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.
- Conditions
- Out-Of-Hospital Cardiac Arrest
- Being tested
- Target Temperature Management of 34°C, Target Temperature Management of 32°C, Target Temperature Management of 33°C
- Keywords
- Target Temperature Management, Cooling comatose survivors from OHCA, Good neurological outcome at modified Rankin Score (mRS) ≤ 3
- Medical subject headings
- Out-of-Hospital Cardiac Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Target Temperature Management of 34°CDevice
In hospital target temperature management to achieve core body temperature of 34°C for 24 hours.
Target Temperature Management of 32°CDevice
In hospital target temperature management to achieve core body temperature of 32°C for 24 hours.
Target Temperature Management of 33°CDevice
In hospital target temperature management to achieve core body temperature of 33°C for 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Target Temperature Management of 34°C | Other | In hospital target temperature management to achieve core body temperature of 34°C for 24 hours. Receives: Device: Target Temperature Management of 34°C |
| Target Temperature Management of 32°C | Other | In hospital target temperature management to achieve core body temperature of 32°C for 24 hours. Receives: Device: Target Temperature Management of 32°C |
| Target Temperature Management of 33°C | Other | In hospital target temperature management to achieve core body temperature of 33°C for 24 hours. Receives: Device: Target Temperature Management of 33°C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest.
Measured: at 90 days after out-of-hospital cardiac arrest
Secondary outcomes (23)
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)
Measured: 24 hours
Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia
Measured: 24 hours
Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia
Measured: 26 hours
Treatment Success: 4. rate of cooling in °C per hour
Measured: Per hour
Treatment Success: 5. rate of rewarming in °C per hour
Measured: Per hour
Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion
Measured: 90 days
Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)
Measured: 90 days
Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion
Measured: 90 days
Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)
Measured: 90 days
Outcomes: 5. Survival at 90 days measured as proportion
Measured: 90 days
Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)
Measured: 90 days
Outcomes: 7. ICU-free survival within 90 days measured in days
Measured: 90 days
Outcomes: 8. Hospital-free survival within 90 days measured in days
Measured: 90 days
Outcomes: 9. Adverse events a. Device related b. Procedure related
Measured: 90 days
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.
Measured: 1 year
Subgroups of Special Interest Age of Patients
18 to 65 years; or (ii) > 65 years.
Measured: Duration of the trial
Timings of initiation of hypothermia
(ii) > 65 years.
Measured: <4 hours of restoration of spontaneous circulation; or > 4 hours
Patient Gender
Subgroups to assess Consistency of Effect
Measured: Male or Female
Observational status of arrest
Measured: Witnessed by EMS; Witnessed by bystanders
Location of cardiac arrest
Measured: Public;Home; or Group residence (e.g. nursing home)
Bystander CPR status:
Measured: Performed; or Not performed.
AED status:
Measured: Applied by layperson;Applied by EMS provider;Not applied
Response time interval from call to initiation of CPR by EMS, among witnessed arrests:
Measured: < 10 minutes;> 10 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study startMar 2014
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Out-Of-Hospital Cardiac ArrestStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- ZOLL Circulation, Inc., USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Instituto de Investigación Hospital Universitario La Paz
- Responsible party
- Sponsor
- Investigators
- Prof. Esteban Lopez-de-Sa, M.D, Principal investigator, Hospital Universitario La Paz. Planta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02035839
- Sponsor's protocol ID
- FROST Trial
- Acronym
- FROST
- Status last verified
- May 2017
- First submitted
- 27 Nov 2013
- Last updated
- 26 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 30343315
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Multicenter Randomized Trial on the Effectiveness of Different Levels of Cooling in Comatose Survivors of Out-of-hospital Cardiac Arrest.
- ClinicalTrials.gov ID
- NCT02035839
- Acronym / sponsor ID
- FROST / FROST Trial
- Conditions
- Out-Of-Hospital Cardiac Arrest
- Keywords
- Target Temperature Management, Cooling comatose survivors from OHCA, Good neurological outcome at modified Rankin Score (mRS) ≤ 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- ZOLL Circulation, Inc., USAIndustry (pharma, biotech, devices)
- Collaborators
- Instituto de Investigación Hospital Universitario La Paz
- Study start
- Mar 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 14 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Target Temperature Management of 34°C | Other | Device: Target Temperature Management of 34°CIn hospital target temperature management to achieve core body temperature of 34°C for 24 hours. |
| Target Temperature Management of 32°C | Other | Device: Target 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°C | Other | Device: Target Temperature Management of 33°CIn hospital target temperature management to achieve core body temperature of 33°C for 24 hours. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (18 listed)
- Traumatic cardiac arrest
- Toxicological etiology
- Known or suspected pregnancy
- Do Not Attempt to Resuscitate order in force
- Unwitnessed arrest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Target Temperature Management of 34°CIn hospital target temperature management to achieve core body temperature of 34°C for 24 hours. | Device | Target Temperature Management of 34°C |
| Target Temperature Management of 32°CIn hospital target temperature management to achieve core body temperature of 32°C for 24 hours. | Device | Target Temperature Management of 32°C |
| Target Temperature Management of 33°CIn hospital target temperature management to achieve core body temperature of 33°C for 24 hours. | Device | Target Temperature Management of 33°C |
Primary outcome
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
23 secondary outcomes
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
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
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
Treatment Success: 4. rate of cooling in °C per hour
Time frame: Per hour
Treatment Success: 5. rate of rewarming in °C per hour
Time frame: Per hour
Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion
Time frame: 90 days
Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)
Time frame: 90 days
Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion
Time frame: 90 days
Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)
Time frame: 90 days
Outcomes: 5. Survival at 90 days measured as proportion
Time frame: 90 days
Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)
Time frame: 90 days
Outcomes: 7. ICU-free survival within 90 days measured in days
Time frame: 90 days
Outcomes: 8. Hospital-free survival within 90 days measured in days
Time frame: 90 days
Outcomes: 9. Adverse events a. Device related b. Procedure related
Time frame: 90 days
Subgroup analysis
Time frame: 1 year
Subgroups of Special Interest Age of Patients
Time frame: Duration of the trial
Timings of initiation of hypothermia
Time frame: <4 hours of restoration of spontaneous circulation; or > 4 hours
Patient Gender
Time frame: Male or Female
Observational status of arrest
Time frame: Witnessed by EMS; Witnessed by bystanders
Location of cardiac arrest
Time frame: Public;Home; or Group residence (e.g. nursing home)
Bystander CPR status:
Time frame: Performed; or Not performed.
AED status:
Time frame: Applied by layperson;Applied by EMS provider;Not applied
Response time interval from call to initiation of CPR by EMS, among witnessed arrests:
Time frame: < 10 minutes;> 10 minutes.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
- Derived from this study: PubMed 30343315Lopez-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Esteban Lopez-de-Sa, M.D principal investigator
Hospital Universitario La Paz. Planta
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Target Temperature Management of 34°C, Target Temperature Management of 32°C and Target Temperature Management of 33°C in people with Out-Of-Hospital Cardiac Arrest, run by ZOLL Circulation, Inc., USA at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02035839, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2018.