Clinical trial NCT05306392: Effects of Induced Moderate Hypothermia on ARDS Patients Under Venovenous ExtraCorporeal Membrane Oxygenation
Official title: Evaluation of the Effectiveness of Induced Moderate Hypothermia in the Management of Patients With Severe ARDS Under Venovenous ECMO
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: ARDS, Human
Extracorporeal Membrane Oxygenation Complication
Hypothermia
Keywords: Hypothermia
ECMO
Refractory hypoxemia
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2022-04-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric controlled study, with randomization in two groups (induced hypothermia group and control group), at the Nancy Hospital - Intensive care Unit
Primary purpose: TREATMENT

Brief summary: Acute respiratory distress syndrome (ARDS) is a lesional pulmonary edema that occurs as a result of direct or indirect lung injury. This condition accounts for 10-15% of ICU admissions and 20-25% of patients admitted require invasive ventilation. Its incidence has increased markedly with the Covid-19 epidemic. ARDS is defined as hypoxemia (Pa02/Fi02 \< 300 mmHg) in ventilated patients without heart failure. Currently, the recommendations of the resuscitation societies advocate a management combining invasive ventilation, short duration curarization and prone sessions. In case of failure of these therapies, venovenous ExtraCorporeal Membrane Oxygenation (VV ECMO) is recommended in case of Pa02/Fi02 \< 80 mmHg.

Nevertheless, approximately 40% of patients have refractory and persistent hypoxemia despite optimization of ECMO parameters and invasive ventilation. The refractory hypoxemia is defined as Pa02 \< 55 mmHg and/or Sa02 \< 90% and may be due to a recirculation phenomenon or a significant intra-pulmonary shunt. Currently, there is no official recommendation for the management of these patients, leading to the use of various unvalidated field practices. In addition, hospital mortality of the order of 60% is observed in these patients with high management costs.

Some data in the literature suggest that induced therapeutic hypothermia (HT) at 34°C for 48 hours could improve the prognosis of these patients by improving oxygenation. Nevertheless, the level of evidence of published studies remains low because they are either case reviews or studies whose methodology does not guarantee the absence of potential bias.

The research hypothesis is that HT at 34°C or 33°C for 48 hours is effective on refractory hypoxemia.

Detailed description: The investigators propose a pilot study, monocentric, prospective, controlled, randomized, to apprehend in an objective and reliable way the effects of induced moderate hypothermia at 34°C, or at 33°C in case of persistence of a Sa02 lower than 90%, during 48 hours in patients under ECMO VV for ARDS. The objective of this study is to show the beneficial effect of the treatment on the patient's oxygenation and to understand the physiopathological mechanism of action at work through different parameters at different times. In parallel, the undesirable effects will be recorded and weighed against the positive effects of the treatment in order to understand the benefit/risk ratio of light HT. The effect on survival will also be evaluated as a secondary objective, not to demonstrate efficacy in this small pilot trial, but to determine the size of the effect that can be expected.

Eligibility criteria: Inclusion Criteria:

* Patients 18 years of age and older
* Intubated, ventilated patients with ARDS requiring VV ECMO
* Family member or trusted person who has been informed about the study and signed the informed consent form or inclusion in an immediate life-threatening situation
* Benefiting from a Social Security affiliation scheme

Exclusion Criteria:

* Presence of a recirculation phenomenon (distance between the 2 ECMO cannulas \< 10 cm).
* Patients expected to die within 48 hours of VV ECMO implantation
* Patients on short-acting beta blockers
* Pregnant, parturient or lactating woman,
* Persons deprived of their liberty by a judicial or administrative decision,
* Minors (non emancipated)
* Adults subject to legal protection measures (guardianship, curatorship, safeguard of justice).
* Person undergoing psychiatric care under articles L3212-1 and L3213-1 of the french Public Health Code

Primary outcomes:
measure: Effectiveness of 48 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
timeFrame: between initiation of hypothermia and 48 hours of induced hypothermia
Secondary outcomes:
measure: Effectiveness of 1 hours, 6 hours, 24 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
timeFrame: at 1 hour, 6 hours, 24 hours of the randomization
measure: Evolution of arterial transport of oxygen during therapeutic hypothermia
timeFrame: Evaluation of arterial transport of oxygen by peripheral gas measurement at 1 hour, 6 hours, 24 hours and 48 hours of hypothermia
measure: Evolution of ECMO flow / cardiac output ratio (expressed in %)
timeFrame: Measurement at 1 hour, 6 hours, 24 hours and 48 hours
measure: Survival of patients hospitalized in intensive care
timeFrame: Measurement following inclusion with a time maximal of 28 days
measure: The duration of VV ECMO during hospitalization in the intensive care unit
timeFrame: Measurement following inclusion with a time maximal of 28 days
measure: The number of days without mechanical ventilation during resuscitation hospitalization
timeFrame: Measurement following inclusion with a time maximal of 28 days
measure: Microcirculatory perfusion and flow variables
timeFrame: at 24 and 48 hours
measure: The safety of induced hypothermia treatment during hospitalization in the intensive care unit (infections, coagulation disorders, cardiac risk).
timeFrame: Measurement following inclusion with a time maximal of 28 days
Other outcomes:
Locations:
Study officials:
affiliation: CHRU NANCY, Nancy, France
name: Bruno LEVY, PhD
role: STUDY_DIRECTOR
affiliation: CHRU NANCY, Nancy, France
name: Nathalie THILLY, PhD
role: STUDY_CHAIR
affiliation: CHRU NANCY, Nancy, France
name: Thomas KLEIN, MD
role: STUDY_CHAIR
References:
citation: Montisci A, Maj G, Zangrillo A, Winterton D, Pappalardo F. Management of refractory hypoxemia during venovenous extracorporeal membrane oxygenation for ARDS. ASAIO J. 2015 May-Jun;61(3):227-36. doi: 10.1097/MAT.0000000000000207.
citation: Levy B, Taccone FS, Guarracino F. Recent developments in the management of persistent hypoxemia under veno-venous ECMO. Intensive Care Med. 2015 Mar;41(3):508-10. doi: 10.1007/s00134-014-3579-y. Epub 2014 Dec 2. No abstract available.
citation: Kimmoun A, Vanhuyse F, Levy B. Improving blood oxygenation during venovenous ECMO for ARDS. Intensive Care Med. 2013 Jun;39(6):1161-2. doi: 10.1007/s00134-013-2903-2. Epub 2013 Apr 13. No abstract available.