Cardiac ArrestOverCoolNCT06798818
Lung-cOnservative Liquid VEntilation for the Induction of Ultra-Rapid COOLing After Cardiac Arrest
A study testing Ultra-rapid therapeutic hypothermia induction by total liquid ventilation in people with Cardiac Arrest and Post Cardiac Arrest Syndrome, run by ORIXHA at 1 site in France.
Trial summary
Out-of-hospital cardiac arrest (OHCA) affects over 356,000 individuals annually in the United States, with fewer than 10% surviving to hospital discharge, mirroring statistics from Europe. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Cardiac Arrest, Post Cardiac Arrest Syndrome
- What is being tested?
- Ultra-rapid therapeutic hypothermia induction by total liquid ventilation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2025to Mar 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient resuscitated after extra- or intra-hospital cardiac arrest, from presumed cardiac or asphyxial origin, regardless of the heart rate initially recorded.
- Age between 18 and 84 years old
- Time between collapse and return of spontaneous circulation (ROSC) < 60 min
- Presumption, at the time of inclusion, of a possibility of starting Vent2Cool within a period of less than 120 min after ROSC.
- Unconscious (GCS <8, not able to obey verbal commands after sustained ROSC)
- Patient affiliated with a social security system (If applicable)
- Consent of the member of patients' family or that of the trusted person if present and able to understand; otherwise certificate of emergency inclusion in compliance with applicable regulations.
- Vent2Cool must be connected to a standard cuffed ETT of 7.0 mm to 9.0 mm internal diameter for the procedure.
Who cannot join
- Conscious patient
- Patient Ideal Body Weight less than 40 kgs or more than 93 kgs
- Traumatic cardiac arrest, drowning, exsanguination, or sepsis
- Temperature at admission < 34.0°C
- Need for veno-arterial extracorporeal circulation (Extracorporeal membrane of oxygenation, ECMO) before return of spontaneous circulation (refractory cardiac arrest)
- One of the following signs at echocardiography at hospital admission:
Show all 23Show fewer
- Acute cor pulmonale, defined by right ventricular enlargement with interventricular septal deviation, associated with a Tricuspid Annular Plane Systolic Excursion (TAPSE) < 12 mm and need for vasopressor agents
- Time-velocity integral of subaortic flow < 10 m/s
- Wrong positioning or damage of the endotracheal tube.
- Women under 50 years old (childbearing age) or for women of >50 years old, a positive pregnancy test (urinary) in case of pregnancy suspicion by the investigator. Possible breastfeeding during the study.
- Suspicion of intracranial bleeding
- History of severe Chronic Obstructive Pulmonary Disease (COPD) with long-term home oxygen therapy
- Acute respiratory pathology (pneumothorax, pleurisy, pneumonia, suspicion of contusion or intra-pulmonary hemorrhage following resuscitation)
- COVID-19 positive test in case of clinical suspicion and/or epidemic context
- Excessive mucus in the upper airways
- Patient presenting at least one of the following criteria in the mechanical ventilation parameters at inclusion:
- PEEP > 8 cm H2O
- Plateau pressure> 25 cmH2O
- Driving pressure> 15cmH2O
- Patient with at least one of the following criteria at inclusion:
- PaO2< 80 mmHg
- PaO2 / FiO2< 150 mmHg
- PaCO2> 48 mmHg
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Hopital Cochin - Service de Medecine intensive et reanimation au 27 rue du Faubourg Saint-Jacques
Paris, 75014
Alain Cariou, M.D.
About this study
Out-of-hospital cardiac arrest (OHCA) affects over 356,000 individuals annually in the United States, with fewer than 10% surviving to hospital discharge, mirroring statistics from Europe. Post-cardiac arrest syndrome (PCAS), a condition causing multi-organ dysfunction, is a leading cause of mortality despite successful resuscitation efforts. Targeted temperature management (TTM) is recommended for comatose patients post-resuscitation to mitigate PCAS, but optimal temperature targets and cooling methods remain unclear. Experimental studies suggest that therapeutic hypothermia (32-34°C), induced rapidly after resuscitation, may provide significant clinical benefits.
Total liquid ventilation (TLV) with breathable liquids has been proposed to achieve ultra-rapid therapeutic hypothermia (URTH). This approach uses the lungs as a heat exchanger to achieve ultra-rapid cooling while maintaining normal gas exchange. It enables a reduction in core body temperature to the hypothermic range (33.0 ± 0.5°C) within 45 minutes in relevant experimental models.
The OverCool study is an open-label, single-arm, multi-centric pilot trial designed to evaluate the performance and safety of Vent2Cool, a medical device intended to induce ultra-rapid therapeutic hypothermia by TLV in resuscitated cardiac arrest patients. The primary objective is to demonstrate Vent2Cool's ability to achieve a target core temperature of 33.0 ± 0.5°C within 60 minutes from start of procedure in resuscitated patients admitted to the Intensive Care Unit following intra- or extra-hospital cardiac arrest. Secondary objectives include assessing procedural safety, cooling performance, feasibility in emergency settings, clinical outcomes, and the impact on biological markers.
Read the detailed description
The "American Heart Association's 2022 Update" estimates that over 356,000 out-of-hospital cardiac arrests (OHCA) occur annually in the United States. These figures are consistant with data from European countries, where fewer than 10% of OHCA patients survive, despite 30% being successfully resuscitated before admission to intensive care units (ICU). The majority of these patients succumb to post-cardiac arrest syndrome (PCAS), a condition characterized by multi-organ failure.
To mitigate the severity of PCAS, current guidelines recommend continuous core temperature monitoring and active fever prevention through targeted temperature management (TTM) in patients who remain comatose following resuscitation from cardiac arrest. While TTM with a target temperature range of 32-36°C has been previously evaluated and applied in specific subpopulations, there is insufficient evidence to universally recommend one target temperature over another within this range. Conversely, experimental studies have demonstrated that the protective effects of therapeutic hypothermia (32-34°C) are strongly influenced by the rate of cooling initiated after resuscitation. These findings suggest that very early application of hypothermia may provide greater benefits compared to simply avoiding fever, emphasizing the importance of timely intervention.
In this context, Total Liquid Ventilation (TLV) with breathable liquids has been investigated in animal studies as a method to achieve ultra-rapid therapeutic hypothermia (URTH) following cardiac arrest. This innovative approach uses the lungs as a potent heat exchanger to achieve ultra-rapid cooling while preserving normal gas exchanges. TLV has demonstrated the capability to lower body core temperature from normothermia to the hypothermic range within 45 minutes, irrespective of body weight, in relevant experimental models. Furthermore, unlike earlier techniques of partial liquid ventilation, this method employs a lung-conservative liquid ventilation approach, which has been shown to be safe. The objective of the present OverCool study is to evaluate the performance and safety of the Vent2Cool device, designed to induce URTH by TLV safely following cardiac arrest.
Accordingly, OverCool is an open-label, single arm, non-comparative, multi-centric pilot study. The study primary objective is to demonstrate the ability of Vent2Cool to achieve a core body temperature of 33.0±0.5°C in less than 60 min after the start of the procedure in resuscitated patients admitted in the ICU after an intra- or extra-hospital cardiac arrest. The main secondary objectives are to demonstrate the safety of the procedure, the cooling performance, the ability to implement the procedure in the emergency setting of post-cardiac arrest management, the clinical outcomes and impact on biological markers.
- Conditions
- Cardiac Arrest, Post Cardiac Arrest Syndrome
- Being tested
- Ultra-rapid therapeutic hypothermia induction by total liquid ventilation
- Keywords
- Cooling, Targeted Temperature Management, ROSC, Resuscitated Cardiac Arrest, Out of Hospital cardiac arrest, Therapeutic Hypothermia, liquid ventilation
- Medical subject headings
- Heart Arrest, Post-Cardiac Arrest Syndrome, Out-of-Hospital Cardiac Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultra-rapid therapeutic hypothermia induction by total liquid ventilationDevice
Vent2Cool System is a targeted temperature management device used to induce ultra-rapid therapeutic hypothermia by total liquid ventilation.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with Vent2Cool device | Experimental | Vent2Cool is to be used to perform induction of Ultra-Rapid Therapeutic Hypothermia for the patients. The hypothermia maintenance and rewarming phases will be performed with an external TTM device as currently used in the investigation centres. Receives: Device: Ultra-rapid therapeutic hypothermia induction by total liquid ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Success rate of the Vent2Cool procedure (safe induction of ultra-rapid therapeutic hypothermia)
The primary end point is the success of the procedure. The success of the procedure is defined as the ability to reach a body core temperature (bladder temperature recommended) of 33.0±0.5°C and a safe return to conventional mechanical ventilation within less than one hour after Vent2Cool start. Start of the Vent2Cool procedure is defined as the opening of the Vent2Cool patient connector valve.
Measured: From start of Vent2Cool procedure to 60min after
Secondary outcomes (7)
modified Rankin Scale (mRS)
mRS will be evaluated at Day 28. The modified Rankin Scale is a scoring system on neurologic function ranging from 0-6, where 0 means no symptoms at all, higher numbers indicating increasing neurologic disabilities and 6 equals death.
Measured: At Day 28
Body Core Temperature
Core temperature (bladder recommended) at start of Vent2Cool procedure and for 36 h after the end of Vent2Cool procedure to include the maintenance and rewarming phases of TTM
Measured: From start of Vent2Cool procedure to 37 hours after
Delay between the start of the Vent2Cool procedure and body core temperature of 33,5°C
Duration in minutes from start of the Vent2Cool procedure (i.e. opening of the Vent2Cool patient connector valve) to Body Core Temperature inferior or equal to 33,5 °C
Measured: During the Vent2Cool procedure
Delay between return of spontaneous circulation (ROSC) and body core temperature of 33.5°C.
Duration in minutes from ROSC to body core temperature inferior or equal to 33,5 °C
Measured: From ROSC to end of Vent2Cool procedure
PaO2 and PaCO2
PaO2 and PaCO2 values from arterial blood gases sampled at inclusion and 10 and 25 minutes into the Vent2Cool procedure
Measured: Inclusion, 10 min and 25 min after start of Vent2Cool procedure
Patient Vital status
Patient Vital status collected at ICU discharge and/or Hospital discharge (if before Day 28) and systematically at Day 28. In case of death : cause of death
Measured: Until Day 28
Glasgow Outcome Score (GOS)
The Glasgow Outcome Scale (GOS) is an ordinal scale used to assess functional outcomes of patients following brain injury.
GOS includes five grades: 5, good recovery; 4, moderate disability; 3, severe disability; 2, persistent vegetative; and 1, death.
Measured: At Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study startMar 2025 (estimated)
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ORIXHA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06798818
- Sponsor's protocol ID
- AR23_0007
- Other IDs
- CIV-24-02-046114
- Acronym
- OverCool
- Status last verified
- Jan 2025
- First submitted
- 22 Jan 2025
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lung-cOnservative Liquid VEntilation for the Induction of Ultra-Rapid COOLing After Cardiac Arrest
- ClinicalTrials.gov ID
- NCT06798818
- Acronym / sponsor ID
- OverCool / AR23_0007
- Conditions
- Cardiac Arrest, Post Cardiac Arrest Syndrome
- Keywords
- Cooling, Targeted Temperature Management, ROSC, Resuscitated Cardiac Arrest, Out of Hospital cardiac arrest, Therapeutic Hypothermia, liquid ventilation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- ORIXHAIndustry (pharma, biotech, devices)
- Study start
- Mar 2025 (estimated)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 29 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Out-of-hospital cardiac arrest (OHCA) affects over 356,000 individuals annually in the United States, with fewer than 10% surviving to hospital discharge, mirroring statistics from Europe. Post-cardiac arrest syndrome (PCAS), a condition causing multi-organ dysfunction, is a leading cause of mortality despite successful resuscitation efforts. Targeted temperature management (TTM) is recommended for comatose patients post-resuscitation to mitigate PCAS, but optimal temperature targets and cooling methods remain unclear. Experimental studies suggest that therapeutic hypothermia (32-34°C), induced rapidly after resuscitation, may provide significant clinical benefits.
Total liquid ventilation (TLV) with breathable liquids has been proposed to achieve ultra-rapid therapeutic hypothermia (URTH). This approach uses the lungs as a heat exchanger to achieve ultra-rapid cooling while maintaining normal gas exchange. It enables a reduction in core body temperature to the hypothermic range (33.0 ± 0.5°C) within 45 minutes in relevant experimental models.
The OverCool study is an open-label, single-arm, multi-centric pilot trial designed to evaluate the performance and safety of Vent2Cool, a medical device intended to induce ultra-rapid therapeutic hypothermia by TLV in resuscitated cardiac arrest patients. The primary objective is to demonstrate Vent2Cool's ability to achieve a target core temperature of 33.0 ± 0.5°C within 60 minutes from start of procedure in resuscitated patients admitted to the Intensive Care Unit following intra- or extra-hospital cardiac arrest. Secondary objectives include assessing procedural safety, cooling performance, feasibility in emergency settings, clinical outcomes, and the impact on biological markers.
Detailed description
The "American Heart Association's 2022 Update" estimates that over 356,000 out-of-hospital cardiac arrests (OHCA) occur annually in the United States. These figures are consistant with data from European countries, where fewer than 10% of OHCA patients survive, despite 30% being successfully resuscitated before admission to intensive care units (ICU). The majority of these patients succumb to post-cardiac arrest syndrome (PCAS), a condition characterized by multi-organ failure.
To mitigate the severity of PCAS, current guidelines recommend continuous core temperature monitoring and active fever prevention through targeted temperature management (TTM) in patients who remain comatose following resuscitation from cardiac arrest. While TTM with a target temperature range of 32-36°C has been previously evaluated and applied in specific subpopulations, there is insufficient evidence to universally recommend one target temperature over another within this range. Conversely, experimental studies have demonstrated that the protective effects of therapeutic hypothermia (32-34°C) are strongly influenced by the rate of cooling initiated after resuscitation. These findings suggest that very early application of hypothermia may provide greater benefits compared to simply avoiding fever, emphasizing the importance of timely intervention.
In this context, Total Liquid Ventilation (TLV) with breathable liquids has been investigated in animal studies as a method to achieve ultra-rapid therapeutic hypothermia (URTH) following cardiac arrest. This innovative approach uses the lungs as a potent heat exchanger to achieve ultra-rapid cooling while preserving normal gas exchanges. TLV has demonstrated the capability to lower body core temperature from normothermia to the hypothermic range within 45 minutes, irrespective of body weight, in relevant experimental models. Furthermore, unlike earlier techniques of partial liquid ventilation, this method employs a lung-conservative liquid ventilation approach, which has been shown to be safe. The objective of the present OverCool study is to evaluate the performance and safety of the Vent2Cool device, designed to induce URTH by TLV safely following cardiac arrest.
Accordingly, OverCool is an open-label, single arm, non-comparative, multi-centric pilot study. The study primary objective is to demonstrate the ability of Vent2Cool to achieve a core body temperature of 33.0±0.5°C in less than 60 min after the start of the procedure in resuscitated patients admitted in the ICU after an intra- or extra-hospital cardiac arrest. The main secondary objectives are to demonstrate the safety of the procedure, the cooling performance, the ability to implement the procedure in the emergency setting of post-cardiac arrest management, the clinical outcomes and impact on biological markers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with Vent2Cool device | Experimental | Device: Ultra-rapid therapeutic hypothermia induction by total liquid ventilationVent2Cool is to be used to perform induction of Ultra-Rapid Therapeutic Hypothermia for the patients. The hypothermia maintenance and rewarming phases will be performed with an external TTM device as currently used in the investigation centres. |
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient resuscitated after extra- or intra-hospital cardiac arrest, from presumed cardiac or asphyxial origin, regardless of the heart rate initially recorded.
- Age between 18 and 84 years old
- Time between collapse and return of spontaneous circulation (ROSC) < 60 min
- Presumption, at the time of inclusion, of a possibility of starting Vent2Cool within a period of less than 120 min after ROSC.
- Unconscious (GCS <8, not able to obey verbal commands after sustained ROSC)
Key exclusion criteria (23 listed)
- Conscious patient
- Patient Ideal Body Weight less than 40 kgs or more than 93 kgs
- Traumatic cardiac arrest, drowning, exsanguination, or sepsis
- Temperature at admission < 34.0°C
- Need for veno-arterial extracorporeal circulation (Extracorporeal membrane of oxygenation, ECMO) before return of spontaneous circulation (refractory cardiac arrest)
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 |
|---|---|---|
| Ultra-rapid therapeutic hypothermia induction by total liquid ventilationVent2Cool System is a targeted temperature management device used to induce ultra-rapid therapeutic hypothermia by total liquid ventilation. | Device | Treatment with Vent2Cool device |
Primary outcome
Success rate of the Vent2Cool procedure (safe induction of ultra-rapid therapeutic hypothermia)
Time frame: From start of Vent2Cool procedure to 60min after
The primary end point is the success of the procedure. The success of the procedure is defined as the ability to reach a body core temperature (bladder temperature recommended) of 33.0±0.5°C and a safe return to conventional mechanical ventilation within less than one hour after Vent2Cool start. Start of the Vent2Cool procedure is defined as the opening of the Vent2Cool patient connector valve.
7 secondary outcomes
modified Rankin Scale (mRS)
Time frame: At Day 28
Body Core Temperature
Time frame: From start of Vent2Cool procedure to 37 hours after
Delay between the start of the Vent2Cool procedure and body core temperature of 33,5°C
Time frame: During the Vent2Cool procedure
Delay between return of spontaneous circulation (ROSC) and body core temperature of 33.5°C.
Time frame: From ROSC to end of Vent2Cool procedure
PaO2 and PaCO2
Time frame: Inclusion, 10 min and 25 min after start of Vent2Cool procedure
Patient Vital status
Time frame: Until Day 28
Glasgow Outcome Score (GOS)
Time frame: At Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultra-rapid therapeutic hypothermia induction by total liquid ventilation in people with Cardiac Arrest and Post Cardiac Arrest Syndrome, run by ORIXHA 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 8 inclusion and 23 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: opening soon, as of the sponsor's last update on 29 Jan 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sandrine Perrotto, PhD (+33187666102, clinical.affairs@orixha.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Success rate of the Vent2Cool procedure (safe induction of ultra-rapid therapeutic hypothermia) (time frame: From start of Vent2Cool procedure to 60min after). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jan 2025.