Clinical trial NCT02035839: Finding the Optimal Cooling tempeRature After Out-of-HoSpiTal Cardiac Arrest
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
Overall status: COMPLETED
Phase: NA
Conditions: Out-Of-Hospital Cardiac Arrest
Keywords: Target Temperature Management
Cooling comatose survivors from OHCA
Good neurological outcome at modified Rankin Score (mRS) ≤ 3
Lead sponsor: ZOLL Circulation, Inc., USA
Sponsor class: INDUSTRY
Collaborators: name: Instituto de Investigación Hospital Universitario La Paz
First posted: 2014-01-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Fraction of subjects surviving with good neurologic outcome(modified Rankin Score (mRS) ≤ 3) at 90 days after out-of-hospital cardiac arrest.
timeFrame: at 90 days after out-of-hospital cardiac arrest
Secondary outcomes:
measure: 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)
timeFrame: 24 hours
measure: Treatment Success: 2. proportion of time at randomly allocated target temperature ±0.3°C during first 24 hours after initiation of induction of hypothermia
timeFrame: 24 hours
measure: Treatment Success: 3. time to randomly allocated target temperature, from call to 911, sustained restoration of circulation and initiation of induction of hypothermia
timeFrame: 26 hours
measure: Treatment Success: 4. rate of cooling in °C per hour
timeFrame: Per hour
measure: Treatment Success: 5. rate of rewarming in °C per hour
timeFrame: Per hour
measure: Outcomes: 1.Favorable neurologic status at 90 days (i.e. mRS < 3) measured as proportion
timeFrame: 90 days
measure: Outcomes: 2.Time to first detected mRS ≤3 (i.e. Kaplan Meier curve)
timeFrame: 90 days
measure: Outcomes: 3.Robust neurologic status at 90 days (i.e. mRS < 2) measured as proportion
timeFrame: 90 days
measure: Outcomes: 4. Time to first detected mRS ≤2 (i.e. Kaplan Meier curve)
timeFrame: 90 days
measure: Outcomes: 5. Survival at 90 days measured as proportion
timeFrame: 90 days
measure: Outcomes: 6. Cumulative incidence of survival at 90 days (i.e. Kaplan Meier curve)
timeFrame: 90 days
measure: Outcomes: 7. ICU-free survival within 90 days measured in days
timeFrame: 90 days
measure: Outcomes: 8. Hospital-free survival within 90 days measured in days
timeFrame: 90 days
measure: Outcomes: 9. Adverse events a. Device related b. Procedure related
timeFrame: 90 days
measure: Subgroup analysis
timeFrame: 1 year
measure: Subgroups of Special Interest Age of Patients
timeFrame: Duration of the trial
measure: Timings of initiation of hypothermia
timeFrame: <4 hours of restoration of spontaneous circulation; or > 4 hours
measure: Patient Gender
timeFrame: Male or Female
measure: Observational status of arrest
timeFrame: Witnessed by EMS; Witnessed by bystanders
measure: Location of cardiac arrest
timeFrame: Public;Home; or Group residence (e.g. nursing home)
measure: Bystander CPR status:
timeFrame: Performed; or Not performed.
measure: AED status:
timeFrame: Applied by layperson;Applied by EMS provider;Not applied
measure: Response time interval from call to initiation of CPR by EMS, among witnessed arrests:
timeFrame: < 10 minutes;> 10 minutes.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: The Charité - Universitätsmedizin Berlin
city: Madrid
country: Spain
facility: Hospital Universitario La Paz. Planta
state: Pso. De La Castellana
city: Alcala de Henares
country: Spain
facility: H. Principe de Asturias
city: Badalona
country: Spain
facility: Germans Trias i Pujol University Hospital
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón.
city: Madrid
country: Spain
facility: Hospital San Carlos
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Santiago de Compostela
country: Spain
facility: H. University of Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitarion Virgen de la Macarena
city: Vitoria
country: Spain
facility: Hospital Universitario Araba Txagorritxu
Study officials:
affiliation: Hospital Universitario La Paz. Planta
name: Prof. Esteban Lopez-de-Sa, M.D
role: PRINCIPAL_INVESTIGATOR
References:
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.