Heart ArrestISOCRATENCT02555254
Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia
A study testing Low Speed of Rewarming and High Speed of Rewarming in people with Heart Arrest and Cardiac Arrest, run by Centre Hospitalier Departemental Vendee at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Arrest, Cardiac Arrest, Hypothermia
- What is being tested?
- Low Speed of Rewarming and High Speed of Rewarming
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteFrance
- Study dates
- 12 Feb 2016to 8 Jun 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia. A Randomized Controlled Pilot Study
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.
Read the 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.
- Conditions
- Heart Arrest, Cardiac Arrest, Hypothermia
- Being tested
- Low Speed of Rewarming, High Speed of Rewarming
- Keywords
- cardiac arrest, targeted temperature management, hypothermia induced, shockable rhythm
- Medical subject headings
- Heart Arrest, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Speed of RewarmingProcedure or surgery
Speed of rewarming will be at 0.25°C/h with specific temperature controlled external device
High Speed of RewarmingProcedure or surgery
Speed of rewarming will be at 0.50°C/h with specific temperature controlled external device
| Study group | Role | What they receive |
|---|---|---|
| Low speed of rewarming | Experimental | 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. Receives: Procedure: Low Speed of Rewarming |
| Fast speed of rewarming | Experimental | 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. Receives: Procedure: High Speed of Rewarming |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target
Median AUC for serum IL6 levels over time
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2015 (estimated)
- Study start12 Feb 2016
- Primary completion17 May 2020
- Study completion8 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Departemental Vendee
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, University Hospital, Tours
- Responsible party
- Sponsor
- Investigators
- Jean Baptiste Lascarrou, MD, Study chair, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02555254
- Sponsor's protocol ID
- CHD 013-15
- Acronym
- ISOCRATE
- Status last verified
- Nov 2025
- First submitted
- 14 Sep 2015
- Last updated
- 2 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Pouplet C, Colin G, Guichard E, Reignier J, Le Gouge A, Martin S, Lacherade JC, Lascarrou JB; AfterROSC network. The accuracy of various neuro-prognostication algorithms and the added value of neurofilament light chain dosage for patients resuscitated from shockable cardiac arrest: An ancillary analysis of the ISOCRATE study. Resuscitation. 2022 Feb;171:1-7. doi: 10.1016/j.resuscitation.2021.12.009. Epub 2021 Dec 13.
PubMed 34915084Lascarrou JB, Guichard E, Reignier J, Le Gouge A, Pouplet C, Martin S, Lacherade JC, Colin G; AfterROSC network. Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 degrees C: the ISOCRATE pilot randomized controlled trial. Crit Care. 2021 Dec 17;25(1):434. doi: 10.1186/s13054-021-03842-9.
PubMed 34920723
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Speed Of Rewarming After CaRdiac Arrest and ThErapeutic Hypothermia. A Randomized Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT02555254
- Acronym / sponsor ID
- ISOCRATE / CHD 013-15
- Conditions
- Heart Arrest, Cardiac Arrest, Hypothermia
- Keywords
- cardiac arrest, targeted temperature management, hypothermia induced, shockable rhythm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Centre Hospitalier Departemental VendeeUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, University Hospital, Tours
- Study start
- 12 Feb 2016 (actual)
- Primary completion
- 17 May 2020 (actual)
- Study completion
- 8 Jun 2020 (actual)
- First posted
- 21 Sep 2015 (estimated)
- Results
- Posted 22 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low speed of rewarming | Experimental | Procedure: Low Speed of RewarmingPatients 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. |
| Fast speed of rewarming | Experimental | Procedure: High Speed of RewarmingPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (15 listed)
- 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
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 |
|---|---|---|
| Low Speed of RewarmingSpeed of rewarming will be at 0.25°C/h with specific temperature controlled external device | Procedure or surgery | Low speed of rewarming |
| High Speed of RewarmingSpeed of rewarming will be at 0.50°C/h with specific temperature controlled external device | Procedure or surgery | Fast speed of rewarming |
Primary outcome
Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target
Time frame: 48 hours
Median AUC for serum IL6 levels over time
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34915084Pouplet C, Colin G, Guichard E, Reignier J, Le Gouge A, Martin S, Lacherade JC, Lascarrou JB; AfterROSC network. The accuracy of various neuro-prognostication algorithms and the added value of neurofilament light chain dosage for patients resuscitated from shockable cardiac arrest: An ancillary analysis of the ISOCRATE study. Resuscitation. 2022 Feb;171:1-7. doi: 10.1016/j.resuscitation.2021.12.009. Epub 2021 Dec 13.
- Results publication: PubMed 34920723Lascarrou JB, Guichard E, Reignier J, Le Gouge A, Pouplet C, Martin S, Lacherade JC, Colin G; AfterROSC network. Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 degrees C: the ISOCRATE pilot randomized controlled trial. Crit Care. 2021 Dec 17;25(1):434. doi: 10.1186/s13054-021-03842-9.
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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.
Jean Baptiste Lascarrou, MD study chair
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low Speed of Rewarming and High Speed of Rewarming in people with Heart Arrest and Cardiac Arrest, run by Centre Hospitalier Departemental Vendee at 1 site in France.
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 4 inclusion and 15 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 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
Yes. Results are posted in the registry (first posted 22 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Serum Il6 Levels Over the 48 Hours Following Achievement of the Thermal Target (time frame: 48 hours). 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 NCT02555254, which also lists 2 linked publications.
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 2 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.