Long Term Follow-up of Cardiac Arrest Survivors Exposed to Ultra-rapid Cooling

Official title

Long Term Follow-up of Cardiac Arrest Survivors Exposed to Ultra-rapid Cooling, a Prospective Non-interventional Cohort

Overview

Less than 10% of patients eliciting out-of-hospital cardiac arrest (OHCA) survive, although 30% can be resuscitated by Emergency services before admission in Intensive Care Units (ICU). The majority succumb to Post-Cardiac Arrest Syndrome (PCAS). PCAS is associated with high mortality (60-70%) and morbidity. One proposed method of preventing the neurological and cardiac consequences of PCAS is to lower the body temperature to 33°C as quickly as possible. This approach is known as therapeutic hypothermia or Targeted Temperature Management (TTM). The Vent2Cool system, developed by Orixha, is a novel approach that enables the rapid induction of therapeutic hypothermia by using hypothermic Total Liquid Ventilation (TLV) to reach a protective temperature of 33°C within minutes. The OverCool feasibility study, which started in April 2025, is designed to validate the clinical performance and safety of an ultra-rapid cooling approach combining ultra-rapid hypothermia induction using the Vent2Cool system, and maintenance and rewarming using the ArcticSun system. The AfterCool study aims to evaluate long-term outcomes during a five-year follow-up of cardiac arrest survivors who were treated with ultrarapid cooling in the OverCool study.

Detailed description

Fewer than 10% of patients experiencing out-of-hospital cardiac arrest (OHCA) survive, although 30% can be resuscitated by emergency services before being admitted to intensive care units (ICUs). Many cardiac arrest patients who are initially resuscitated by first responders and/or EMS, however, are condemned to a 'second death' in the ICU due to severe neurological and multi-visceral sequelae from post-cardiac arrest syndrome (PCAS).

One proposed method of preventing the neurological and cardiac complications of PCAS is to lower the body temperature to 33°C as quickly as possible. This approach is known as therapeutic hypothermia or Targeted Temperature Management (TTM). However, the cooling power of available technologies is insufficient to induce therapeutic hypothermia, and they do not improve outcomes for most patients. Conversely, experimental reports clearly demonstrate that therapeutic hypothermia can dramatically improve clinical outcomes if applied within two to three hours of resuscitation.

The devices currently available for TTM are mostly external cooling devices, such as blankets, pads and suits. These devices have a cooling performance of less than 1°C per hour in the body's core and in vital organs with high blood flow. Orixha's Vent2Cool is a novel approach that enables the induction of ultra-rapid therapeutic hypothermia (URTH) by using hypothermic total liquid ventilation (TLV) to reach a protective temperature of 33°C within minutes.

The OverCool feasibility study, which has been approved by the French authorities and began enrolment in early 2025, is designed to test the feasibility of ultra-rapid cooling. It aims to validate the clinical performance and safety of an ultra-rapid cooling approach combining ultra-rapid hypothermia induction using the Vent2Cool system, and maintenance and rewarming using the ArcticSun system. OverCool will pave the way for other clinical investigations to demonstrate the superior clinical benefits of this new approach to hypothermic TTM compared to the standard of care.

The AfterCool study will follow cardiac arrest survivors who were treated with ultrarapid cooling in the Overcool study for five years. The AfterCool approach aligns with the need to evaluate long-term outcomes after cardiac arrest, as endorsed by the French AfterROSC network, which supports research into post-cardiac arrest patients.

Eligible subjects, after having received clear, impartial and complete information, and not having objected to participation in the study, will be included. At the inclusion visit, a detailed questionnaire regarding life status, quality of life, putative rehospitalization, cardiovascular, neurological and respiratory status will be administered.

At 6±1 months and 12±1 months after inclusion, and then yearly during a total period of 5 years, the patients or trusted persons or the close relatives or parents will be interviewed by phone, using the same questionnaire regarding life status, quality of life, putative rehospitalization, cardiovascular, neurological and respiratory status.

Interventions

• Other Short Form Health Survey (SF-36)
  Heath-related quality-of-life is assessed using the SF-36 questionnaire, which is administered at the inclusion visite, then at month 6, year 1, year 2, year 3, year 4 and year 5, in the form of a telephone interview.
• Other Modified Rankin Score (mRS)
  The degree of disability/dependence is evaluated using the mRS scale at the inclusion visite, then at month 6, year 1, year 2, year 3, year 4 and year 5, via telephone interview.
• Other Activity of Daily Living (ADL) questionnaire
  Level of independence is evaluated using the ADL questionnaire, which is administered at the inclusion visite, then at month 6, year 1, year 2, year 3, year 4 and year 5, in the form of a telephone interview.
• Other New York Heart Association (NYHA) Classification
  The extent of heart failure is assessed using the NYHA functional classification at the inclusion visite, then at month 6, year 1, year 2, year 3, year 4 and year 5, via telephone interview.
• Other St George's Respiratory Questionnaire (SGRQ)
  Respiratory status is assessed using the SGRQ questionnaire at the inclusion visite, then at month 6, year 1, year 2, year 3, year 4 and year 5, via telephone interview.

Primary outcome measures

• Life status at 5 years [Time frame: 5 years]

Secondary outcome measures (10)

• Suspected cause of death [Time frame: 5 years]
• Rehospitalization [Time frame: 5 years]
• Modified Rankin Scale (mRS) Score [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• 36-Item Short Form Health Survey (SF-36) score [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• Activity of Daily Living (ADL) score [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• Cardiovascular adverse events [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• NewYork Health Association (NYHA) status [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• Respiratory adverse events [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• St-George's Respiratory Questionnaire (SGRQ) Score [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]
• Home oxygen therapy [Time frame: Baseline, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years]

Eligibility criteria

Inclusion criteria

• Age of 18 years and over
• Cardiac arrest patient included in and alive at the end of the OverCool clinical investigation (28 days after the cardiac arrest)
• Non-opposition from the patient or the trusted person or the close relative or parent obtained within 3 months after the end of the OverCool study

Exclusion criteria

• Follow-up refusal from patient of trusted person or the close relative or parent
• Having being included in the OverCool clinical investigation but not submitted to the Vent2Cool procedure
• Impossibility to reach the patient or the trusted person or the close relative or parent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 2 centers

• Angers University Hospital, Medical Intensive Care Unit, Vent'Lab — Angers
• AP-HP Centre, Cochin Hospital, Medical Intensive Care Unit — Paris

Publications

• Tissier R, Taccone FS, Lamhaut L, Vicaut E, Paublant F, Ricard JD, Mercat A, Cariou A. Design of the OverCool study: Lung-conservative liquid ventilation for the induction of Ultra-Rapid Cooling after Cardiac Arrest (OverCool). Resusc Plus. 2025 Mar 10;23:100926. doi: 10.1016/j.resplu.2025.100926. eCollection 2025 May. PMID 40212905
• Dumas F, Paoli A, Paul M, Savary G, Jaubert P, Chocron R, Varenne O, Mira JP, Charpentier J, Bougouin W, Cariou A. Association between previous health condition and outcome after cardiac arrest. Resuscitation. 2021 Oct;167:267-273. doi: 10.1016/j.resuscitation.2021.06.017. Epub 2021 Jul 7. PMID 34245838
• Bougouin W, Lascarrou JB, Chelly J, Benghanem S, Geri G, Maizel J, Fage N, Sboui G, Pichon N, Daubin C, Sauneuf B, Mongardon N, Taccone F, Hermann B, Colin G, Lesieur O, Deye N, Chudeau N, Cour M, Bourenne J, Klouche K, Klein T, Raphalen JH, Muller G, Galbois A, Bruel C, Jacquier S, Paul M, Sandroni C, Cariou A. Performance of the ERC/ESICM-recommendations for neuroprognostication after cardiac ar PMID 39151721
• Flajoliet N, Bourenne J, Marin N, Chelly J, Lascarrou JB, Daubin C, Bougouin W, Cariou A, Geri G. Return to work after out of hospital cardiac arrest, insights from a prospective multicentric French cohort. Resuscitation. 2024 Jun;199:110225. doi: 10.1016/j.resuscitation.2024.110225. Epub 2024 Apr 27. PMID 38685375
• Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J; CRICS-TRIGGERSEP Group. Targeted Temperature Management for Cardiac Arrest wit PMID 31577396
• Arrich J, Herkner H, Mullner D, Behringer W. Targeted temperature management after cardiac arrest. A systematic review and meta-analysis of animal studies. Resuscitation. 2021 May;162:47-55. doi: 10.1016/j.resuscitation.2021.02.002. Epub 2021 Feb 12. PMID 33582259
• Kohlhauer M, Lidouren F, Remy-Jouet I, Mongardon N, Adam C, Bruneval P, Hocini H, Levy Y, Blengio F, Carli P, Vivien B, Ricard JD, Micheau P, Walti H, Nadeau M, Robert R, Richard V, Mulder P, Maresca D, Demene C, Pernot M, Tanter M, Ghaleh B, Berdeaux A, Tissier R. Hypothermic Total Liquid Ventilation Is Highly Protective Through Cerebral Hemodynamic Preservation and Sepsis-Like Mitigation After A PMID 26110489
• Darbera L, Chenoune M, Lidouren F, Kohlhauer M, Adam C, Bruneval P, Ghaleh B, Dubois-Rande JL, Carli P, Vivien B, Ricard JD, Berdeaux A, Tissier R. Hypothermic liquid ventilation prevents early hemodynamic dysfunction and cardiovascular mortality after coronary artery occlusion complicated by cardiac arrest in rabbits. Crit Care Med. 2013 Dec;41(12):e457-65. doi: 10.1097/CCM.0b013e3182a63b5d. PMID 24126441

Identifiers

NCT: NCT07028372 · APHP250360 · 2025-A00442-47

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗