Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia

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

Sponsors

Lead Sponsor: Centre Hospitalier Departemental Vendee

Collaborator: Institut National de la Santé Et de la Recherche Médicale, France
University Hospital, Tours

Source Centre Hospitalier Departemental Vendee
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.

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.

Overall Status Recruiting
Start Date February 12, 2016
Completion Date November 2019
Primary Completion Date July 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Interleukine 6 Dosage 36 hours
Secondary Outcome
Measure Time Frame
Neurological functional prognosis Day 90
Mortality in the ICU ICU Discharge (expected day 10)
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)
Incidence of aspiration pneumonia Day 2
Incidence of nosocomial bacteremia in ICU ICU Discharge (Expected day 10)
Incidence of nosocomial intravascular catheter infections in ICU ICU Discharge (Expected day 10)
Comparison of Interleukine 2 36 hours
Comparison of Interleukine 4 36 hours
Comparison of Interleukine 8 36 hours
Comparison of Interleukine 10 36 hours
Comparison of GM-CSF 36 hours
Comparison of Interferon Beta 36 hours
Comparison of TNF-Alpha 36 hours
Enrollment 60
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Low Speed of Rewarming

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

Arm Group Label: Low speed of rewarming

Intervention Type: Procedure

Intervention Name: High Speed of Rewarming

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

Arm Group Label: Fast speed of rewarming

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Jean Baptiste Lascarrou, MD Study Chair CHU Nantes
Overall Contact

Last Name: Jean-Baptiste Lascarrou, MD

Phone: +33251446212

Email: [email protected]

Location
Facility: Status: Contact: Colin Gwenhael Gwenhael Colin, M.D. +33251446212 [email protected]
Location Countries

France

Verification Date

January 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Low speed of rewarming

Type: Experimental

Description: 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.

Label: Fast speed of rewarming

Type: Experimental

Description: 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.

Acronym ISOCRATE
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov