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

Out-Of-Hospital Cardiac Arrest Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02035839
• Other study ID #: FROST Trial
• Status: Completed
• Phase: N/A
• Start date: March 2014
• Est. completion date: April 2016

Study information

• Verified date: May 2017
• Source: ZOLL Circulation, Inc., USA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Arrest
• Out-of-Hospital Cardiac Arrest

Intervention

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

Locations

Country	Name	City	State
Germany	The Charité - Universitätsmedizin Berlin	Berlin
Spain	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	Hospital San Carlos	Madrid
Spain	Hospital Universitario La Paz. Planta	Madrid	Pso. De La Castellana
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 Universitario Araba Txagorritxu	Vitoria

Sponsors (2)

Lead Sponsor	Collaborator
ZOLL Circulation, Inc., USA	Instituto de Investigación Hospital Universitario La Paz

Countries where clinical trial is conducted

Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia		24 hours
Secondary	Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia		26 hours
Secondary	Treatment Success: 4. rate of cooling in °C per hour		Per hour
Secondary	Treatment Success: 5. rate of rewarming in °C per hour		Per hour
Secondary	Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion		90 days
Secondary	Outcomes: 2.Time to first detected mRS =3 (i.e. Kaplan Meier curve)		90 days
Secondary	Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion		90 days
Secondary	Outcomes: 4. Time to first detected mRS =2 (i.e. Kaplan Meier curve)		90 days
Secondary	Outcomes: 5. Survival at 90 days measured as proportion		90 days
Secondary	Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)		90 days
Secondary	Outcomes: 7. ICU-free survival within 90 days measured in days		90 days
Secondary	Outcomes: 8. Hospital-free survival within 90 days measured in days		90 days
Secondary	Outcomes: 9. Adverse events a. Device related b. Procedure related		90 days
Secondary	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.	1 year
Secondary	Subgroups of Special Interest Age of Patients	18 to 65 years; or (ii) > 65 years.	Duration of the trial
Secondary	Timings of initiation of hypothermia	(ii) > 65 years.	<4 hours of restoration of spontaneous circulation; or > 4 hours
Secondary	Patient Gender	Subgroups to assess Consistency of Effect	Male or Female
Secondary	Observational status of arrest		Witnessed by EMS; Witnessed by bystanders
Secondary	Location of cardiac arrest		Public;Home; or Group residence (e.g. nursing home)
Secondary	Bystander CPR status:		Performed; or Not performed.
Secondary	AED status:		Applied by layperson;Applied by EMS provider;Not applied
Secondary	Response time interval from call to initiation of CPR by EMS, among witnessed arrests:		< 10 minutes;> 10 minutes.

External Links

•   Pilot trial comparing 2 levels of target temperature. Circulation. 2012;126:2826-2833