Clinical trial NCT06798818: Lung-cOnservative Liquid VEntilation for the Induction of Ultra-Rapid COOLing After Cardiac Arrest
Official title: Lung-cOnservative Liquid VEntilation for the Induction of Ultra-Rapid COOLing After Cardiac Arrest
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: ORIXHA
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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:

  * 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

Primary outcomes:
measure: Success rate of the Vent2Cool procedure (safe induction of ultra-rapid therapeutic hypothermia)
timeFrame: From start of Vent2Cool procedure to 60min after
Secondary outcomes:
measure: modified Rankin Scale (mRS)
timeFrame: At Day 28
measure: Body Core Temperature
timeFrame: From start of Vent2Cool procedure to 37 hours after
measure: Delay between the start of the Vent2Cool procedure and body core temperature of 33,5°C
timeFrame: During the Vent2Cool procedure
measure: Delay between return of spontaneous circulation (ROSC) and body core temperature of 33.5°C.
timeFrame: From ROSC to end of Vent2Cool procedure
measure: PaO2 and PaCO2
timeFrame: Inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Patient Vital status
timeFrame: Until Day 28
measure: Glasgow Outcome Score (GOS)
timeFrame: At Day 28
Other outcomes:
measure: Cooling Rate in body core temperature
timeFrame: During the Vent2Cool procedure
measure: Occurence of cooling overshoot
timeFrame: From start of Vent2Cool procedure to 60min after.
measure: Early termination of the Vent2Cool procedure by the clinician before reaching a core target temperature below 33±0.5°C (failure of cooling induction)
timeFrame: During the Vent2Cool procedure
measure: modified Cardiac Arrest Hospital Prognosis (mCAHP) Score
timeFrame: At inclusion
measure: Prognostication according to the modified Cardiac Arrest Hospital Prognosis (mCAHP) score
timeFrame: At inclusion
measure: Neurofilament light chain (NFL)
timeFrame: At inclusion, Day1 and Day3
measure: Neuron Specific Enolase (NSE)
timeFrame: At inclusion, Day 1 and Day 3
measure: Heart rate measured from the EKG or invasive blood pressure signal
timeFrame: At inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Systemic systolic and diastolic invasive blood pressure
timeFrame: At inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Presence of arrhythmia or unexpected electrocardiographic abnormality on EKG examination during Vent2Cool procedure
timeFrame: During the Vent2Cool procedure
measure: Occurrence of an episode of major systemic hypotension (invasive or non-invasive measurement) with systolic blood pressure < 60 mmHg during Vent2Cool procedure
timeFrame: During the Vent2Cool procedure
measure: Presence or absence of pleural collection of perfluorocarbon in the lungs on thoracic computed tomography examination in patients surviving on Day 28 after cardiac arrest.
timeFrame: Day 28
measure: Glasgow Coma Scale score
timeFrame: At inclusion, at Day 3 and at Day 28.
measure: SOFA score
timeFrame: At Day 1 and Day 3
measure: Percentage of patient with pulmonary infection
timeFrame: At Day 3
measure: Oxygen desaturation based on SpO2
timeFrame: During Vent2Cool procedure.
measure: Number and percentage of patients with severe hypercapnia
timeFrame: At inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Number and Percentage of patients with severe hyperoxemia
timeFrame: At inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Number and Percentage of patients with hypoxemia
timeFrame: At inclusion, 10 min and 25 min after start of Vent2Cool procedure
measure: Pupillometry examination
timeFrame: Day 1 to Day 3
measure: Time of start of Vent2Cool procedure from the time of return of spontaneous circulation (ROSC)
timeFrame: From return of spontaneous circulation to start of Vent2Cool procedure
measure: Time of start of Vent2Cool procedure from the patient's admission to ICU
timeFrame: From patient admission to ICU to start of Vent2Cool procedure
measure: Duration of the Vent2Cool procedure
timeFrame: From the start of the Vent2Cool procedure to the end of the procedure
measure: Vent2Cool performance parameters
timeFrame: During Vent2Cool procedure.
measure: Ventilatory parameters after Vent2Cool procedure
timeFrame: At 1h, 2h, 12h, 24h, 48h and 72h after the start of the Vent2Cool procedure
measure: Hospital Care data
timeFrame: Until Day 28
Locations:
city: Paris
country: France
facility: Hopital Cochin - Service de Medecine intensive et reanimation au 27 rue du Faubourg Saint-Jacques
Study officials:
References: