ISOCRATE: Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia

Sponsor

Centre Hospitalier Departemental Vendee (Other)

Overall Status

Completed

CT.gov ID

NCT02555254

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other), University Hospital, Tours (Other)

Enrollment

Location

Arms

51.8

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Comparing the production of interleukin 6 (inflammatory cytokine) in two heating speed (slow rewarming rate: 0.25 ° C / h or fast rewarming rate 0.50 ° C / h) at the completion of a period of targeted temperature at 33°C after cardiac arrest supported by shockable rhythm and successfully resuscitated.

Condition or Disease	Intervention/Treatment	Phase
Heart Arrest Cardiac Arrest Hypothermia	Procedure: Low Speed of Rewarming Procedure: High Speed of Rewarming	N/A

Detailed Description

Cardiac arrest (CA) is at present a major cause of mortality as well as a cause of disability for the surviving victims. In France, every year counts as 50,000 cardiac arrests responsible for 40 000 deaths. Thus, less than 20% of patients with heart failure discharged home. Then these patients had impaired quality of life associated with symptoms of fatigue, stress, anxiety hindering the resumption of business activity including. The prognosis is related in part to the initial cardiac rhythm present at the establishment of specialized resuscitation.

Recent progress in improving mortality and neurological outcome has been achieved over the last decade with systematic implementation of a period of targeted temperature management between 32 and 34 ° C (TTM 32-34) in patients with cardiac arrest and who benefited from the completion of at least one external electrical shock when help arrived. The mechanisms underlying this improvement of neurological prognosis are many, but mainly related to an attenuation of post resuscitation syndrome that combines in one hand an inflammatory response (mediated by pro-inflammatory cytokines including interleukin 6) and secondly the formation of reperfusion injury related to the production of radical oxygen species (free radicals).

While some studies have shown the feasibility of induction of this TTM 32-34 in prehospital conditions, no prospective study has evaluated the significant speed of warming in the end. An observational study in which the heating was carried passively, found that patients with an extended heating period (600 minutes) had a worse neurological outcome than patients with a duration of shorter warming (479 minutes) while a second retrospective study concluded the opposite in case of active warming . Besides the fact that these studies were observational, in the two originals randomized studies on TTM 32-34 in CA, the rate of warming was not like:

Objective 6 hours with active warming is 0.5 ° C / h in the Australian study with an OR of 5.25 (1.47 - 18.76) for the neurological prognosis
Objective 8 hours with passive warming of 0.37 ° C / h in the European study with an OR of 1.4 (1.08 - 1.81) for the neurological prognosis Although populations of two studies are obviously not comparable, it is possible that suboptimal speed of rewarming could mitigate some of the gain related to the implementation of TTM 32-34.

In this context, investigators propose to conduct a randomized, single-center pilot study comparing a fast warming in a slow warming when performing a TTM 33 patients presented with a shockable cardiac arrest.

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia. A Randomized Controlled Pilot Study

Actual Study Start Date :

Feb 12, 2016

Actual Primary Completion Date :

May 17, 2020

Actual Study Completion Date :

Jun 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low speed of rewarming Patients will be placed in targeted temperature controlled at 33°C for 24 hours. Then, intervention will be proceeded after randomization: slowly rewarmed (0.25°C/h) to targeted temperature controlled at 37°C for 24 hours.	Procedure: Low Speed of Rewarming Speed of rewarming will be at 0.25°C/h with specific temperature controlled external device
Experimental: Fast speed of rewarming Patients will be placed in targeted temperature controlled at 33°C for 24 hours. hen, intervention will be proceeded after randomization: fastly rewarmed (0.50°C/h) for targeted temperature controlled at 37°C for 24 hours.	Procedure: High Speed of Rewarming Speed of rewarming will be at 0.50°C/h with specific temperature controlled external device

Arm

Intervention/Treatment

Experimental: Low speed of rewarming

Patients will be placed in targeted temperature controlled at 33°C for 24 hours. Then, intervention will be proceeded after randomization: slowly rewarmed (0.25°C/h) to targeted temperature controlled at 37°C for 24 hours.

Procedure: Low Speed of Rewarming

Speed of rewarming will be at 0.25°C/h with specific temperature controlled external device

Experimental: Fast speed of rewarming

Patients will be placed in targeted temperature controlled at 33°C for 24 hours. hen, intervention will be proceeded after randomization: fastly rewarmed (0.50°C/h) for targeted temperature controlled at 37°C for 24 hours.

Procedure: High Speed of Rewarming

Speed of rewarming will be at 0.50°C/h with specific temperature controlled external device

Outcome Measures

Primary Outcome Measures

Interleukine 6 Dosage [48 hours]
Evolution of serum levels of Il6 (inflammation marker) measured 6 times between H0 (time of obtaining the thermal target) and H48

Secondary Outcome Measures

Neurological functional prognosis [Day 90]
Glasgow-Pittsburgh Cerebral Performance Category Score
Quality of Life-SF-36 score [Day 90]
36 items-Short Form for Health Survey telephonic interview
Life Autonomy [Day 90]
Modified Barthel, Index for activities of daily living (ADL) and two normative questions about life autonomy
Neurocognitive evaluation [Day 90]
Telephonic validated version of Mini mental state examination
Post traumatic stress disorders [Day 90]
Impact Event Scale-Revised
Mortality in the ICU [ICU Discharge (expected day 10)]
Mortality at hospital [Hospital Discharge (expected 20 days)]
Mortality at day 90 [Day 90]
Duration of hospitalization in ICU [ICU Discharge (expected day 10)]
Duration of mechanical ventilation [Weaning of mechanical ventilation (expected day 7)]
Comparison of Interleukine 2 [48 hours]
Comparison of Interleukine 4 [48 hours]
Comparison of Interleukine 8 [48 hours]
Comparison of Interleukine 10 [48 hours]
Comparison of GM-CSF [48 hours]
Comparison of TNF-Alpha [48 hours]
Comparison of serum neurofilament [48 hours]
Comparison of CRP serum level [first seven days after admission]
Comparison of procalcitonin serum level [first seven days after admission]
Need for vasopressor treatment [72 first hours after ICU admission]
vasopressor dose (Noradenaline or adrenalin)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient has been supported for a shockable cardiac arrest with successful resuscitation.
Coma persistent at ICU admission (Glasgow score less than or equal to 8) in the absence of sedation. If the patient is sedated in ICU admission, the glasgow score will be held the last evaluated by the doctor who provided the pre-hospital care of the patient score.
Body temperature> 33 ° C
Specific device used to targeted temperature management at 33°C

Exclusion Criteria:

Lack of witness of cardiac arrest.
Duration of no-flow> 10 minutes (time between the onset of cardiac arrest and the start of external cardiac massage).
Duration of low-flow> 60 minutes (the period between the start of external cardiac massage and recovery of an effective cardiac activity).
Major hemodynamic instability (dose norepinephrine and / or epinephrine > 1 µg / kg / min to maintain MAP> 65 mmHg).
Time between cardiac arrest and more than 480 minutes inclusion
Moribund.
Presence of histologically confirmed cirrhosis of Child class C.
Patient treatment in blocking the production of Il6 (Ro-tocilizumab or Actemra ®)
Patient under corticosteroid treatment (dose> 5 mg of prednisolone equivalent)
Pregnant woman, parturient or lactating.
Inpatient without consent and / or deprived of liberty by a court decision.
Patient under guardianship
Inclusion in advance a research protocol with the draw, and whose primary endpoint is on interleukin-6.
Lack of social security.
Refusal of the trusted person or patient.