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Effects of Induced Moderate Hypothermia on ARDS Patients Under Venovenous ExtraCorporeal Membrane Oxygenation (HypoLungECMO)

Primary Purpose

ARDS, Human, Extracorporeal Membrane Oxygenation Complication, Hypothermia

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Moderate Hypothermia
Normothermia
Sponsored by
Central Hospital, Nancy, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ARDS, Human focused on measuring Hypothermia, ECMO, Refractory hypoxemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Sham Comparator

    Arm Label

    Moderate Hypothermia

    Control - Normothermia

    Arm Description

    Patients with acute respiratory distress syndrome treated with venovenous ECMO to a strategy of moderate hypothermia during 48 hours (Temperature at 33°C≤ T°C ≤34°C) associated with usual care

    Patients with acute respiratory distress syndrome treated with venovenous ECMO to a strategy of normothermia (36°C≤ T°C ≤37°C) associated with usual care

    Outcomes

    Primary Outcome Measures

    Effectiveness of 48 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
    Hypoxemia is measured by arterial saturation of oxygen (expressed in %)

    Secondary Outcome Measures

    Effectiveness of 1 hours, 6 hours, 24 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
    Hypoxemia is measured by arterial saturation of oxygen (expressed in %)
    Evolution of arterial transport of oxygen during therapeutic hypothermia
    Arterial transport of oxygen is measured by blood gas at different hours (expressed in mL · min-1 · m-2)
    Evolution of ECMO flow / cardiac output ratio (expressed in %)
    Evaluation of the impact of induced hypothermia on the evolution of the ratio of ECMO flow (expressed in L/min) to the patient's cardiac output (assessed by cardiac ultrasound and expressed in L/min). The ratio of ECMO output to patient's cardiac output (expressed in percentage) is calculated as the ratio of ECMO output (expressed in L/min) to cardiac output (expressed in L/min)
    Survival of patients hospitalized in intensive care
    The percentage of patients who died during resuscitation hospitalization
    The duration of VV ECMO during hospitalization in the intensive care unit
    The duration of VV ECMO (in days) during resuscitation hospitalization,
    The number of days without mechanical ventilation during resuscitation hospitalization
    The number of days without invasive mechanical ventilation during resuscitation hospitalization
    Microcirculatory perfusion and flow variables
    measurement of sublingual microcirculation by using Sidestream Dark Field (SDF) microscopy SDF will be applied to the sublingual microvascular network with a 5X objective providing a 167X magnification. After the removal of saliva and other secretions using gauze, the device will be gently applied (without any pressure) on the lateral side of the tongue, in an area approximately 1.5-4 cm from the tip of the tongue. Five sequences of 20 secs each from different adjacent areas will be recorded using a computer and a video card and stored under a random number for later analysis. Other Name: SDF ((Microscan; Microvision Medical, Amsterdam, the Netherlands)
    The safety of induced hypothermia treatment during hospitalization in the intensive care unit (infections, coagulation disorders, cardiac risk).
    For infectious risk: % of infections during hospitalization in the intensive care unit (maximum follow-up time of 28 days); For risk on coagulation: (i) plasma free hemoglobinemia (expressed in g per 100 mL), and on (ii) prothrombin level (expressed in %), at 48 hours; (iii) Need for blood transfusion with hemoglobin loss of more than 2 points within 48 hours of hypothermia (expressed in number of blood transfusion) (iv) Bleeding manifestations within 48 hours with or without need for surgical treatment; For cardiac risk: (i) percentage of patients with symptomatic cardiac rhythm disturbance requiring specific treatment between H0 and H24 and between H0 and H48 (expressed in percentage), (ii) total duration of vasopressors administered at H24 and at H48 (expressed in days)

    Full Information

    First Posted
    February 16, 2022
    Last Updated
    March 23, 2022
    Sponsor
    Central Hospital, Nancy, France
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05306392
    Brief Title
    Effects of Induced Moderate Hypothermia on ARDS Patients Under Venovenous ExtraCorporeal Membrane Oxygenation
    Acronym
    HypoLungECMO
    Official Title
    Evaluation of the Effectiveness of Induced Moderate Hypothermia in the Management of Patients With Severe ARDS Under Venovenous ECMO
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2022 (Anticipated)
    Primary Completion Date
    March 2024 (Anticipated)
    Study Completion Date
    September 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Central Hospital, Nancy, France

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    ARDS, Human, Extracorporeal Membrane Oxygenation Complication, Hypothermia
    Keywords
    Hypothermia, ECMO, Refractory hypoxemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Monocentric controlled study, with randomization in two groups (induced hypothermia group and control group), at the Nancy Hospital - Intensive care Unit
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Moderate Hypothermia
    Arm Type
    Experimental
    Arm Description
    Patients with acute respiratory distress syndrome treated with venovenous ECMO to a strategy of moderate hypothermia during 48 hours (Temperature at 33°C≤ T°C ≤34°C) associated with usual care
    Arm Title
    Control - Normothermia
    Arm Type
    Sham Comparator
    Arm Description
    Patients with acute respiratory distress syndrome treated with venovenous ECMO to a strategy of normothermia (36°C≤ T°C ≤37°C) associated with usual care
    Intervention Type
    Device
    Intervention Name(s)
    Moderate Hypothermia
    Intervention Description
    moderate hypothermia will be induced using the heat controller of the VV-ECMO circuit. Temperature will be maintained between 33°C≤ T°C ≤34°C during 48 hours followed by a progressive reheating (0.2±0.1°C/h) to reach 36 °C. Temperature at 36°C will be maintained during 48 hours after having reached 36 °C.
    Intervention Type
    Device
    Intervention Name(s)
    Normothermia
    Intervention Description
    Temperature at 36°C will be maintained during 48 hours after having reached 36 °C
    Primary Outcome Measure Information:
    Title
    Effectiveness of 48 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
    Description
    Hypoxemia is measured by arterial saturation of oxygen (expressed in %)
    Time Frame
    between initiation of hypothermia and 48 hours of induced hypothermia
    Secondary Outcome Measure Information:
    Title
    Effectiveness of 1 hours, 6 hours, 24 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
    Description
    Hypoxemia is measured by arterial saturation of oxygen (expressed in %)
    Time Frame
    at 1 hour, 6 hours, 24 hours of the randomization
    Title
    Evolution of arterial transport of oxygen during therapeutic hypothermia
    Description
    Arterial transport of oxygen is measured by blood gas at different hours (expressed in mL · min-1 · m-2)
    Time Frame
    Evaluation of arterial transport of oxygen by peripheral gas measurement at 1 hour, 6 hours, 24 hours and 48 hours of hypothermia
    Title
    Evolution of ECMO flow / cardiac output ratio (expressed in %)
    Description
    Evaluation of the impact of induced hypothermia on the evolution of the ratio of ECMO flow (expressed in L/min) to the patient's cardiac output (assessed by cardiac ultrasound and expressed in L/min). The ratio of ECMO output to patient's cardiac output (expressed in percentage) is calculated as the ratio of ECMO output (expressed in L/min) to cardiac output (expressed in L/min)
    Time Frame
    Measurement at 1 hour, 6 hours, 24 hours and 48 hours
    Title
    Survival of patients hospitalized in intensive care
    Description
    The percentage of patients who died during resuscitation hospitalization
    Time Frame
    Measurement following inclusion with a time maximal of 28 days
    Title
    The duration of VV ECMO during hospitalization in the intensive care unit
    Description
    The duration of VV ECMO (in days) during resuscitation hospitalization,
    Time Frame
    Measurement following inclusion with a time maximal of 28 days
    Title
    The number of days without mechanical ventilation during resuscitation hospitalization
    Description
    The number of days without invasive mechanical ventilation during resuscitation hospitalization
    Time Frame
    Measurement following inclusion with a time maximal of 28 days
    Title
    Microcirculatory perfusion and flow variables
    Description
    measurement of sublingual microcirculation by using Sidestream Dark Field (SDF) microscopy SDF will be applied to the sublingual microvascular network with a 5X objective providing a 167X magnification. After the removal of saliva and other secretions using gauze, the device will be gently applied (without any pressure) on the lateral side of the tongue, in an area approximately 1.5-4 cm from the tip of the tongue. Five sequences of 20 secs each from different adjacent areas will be recorded using a computer and a video card and stored under a random number for later analysis. Other Name: SDF ((Microscan; Microvision Medical, Amsterdam, the Netherlands)
    Time Frame
    at 24 and 48 hours
    Title
    The safety of induced hypothermia treatment during hospitalization in the intensive care unit (infections, coagulation disorders, cardiac risk).
    Description
    For infectious risk: % of infections during hospitalization in the intensive care unit (maximum follow-up time of 28 days); For risk on coagulation: (i) plasma free hemoglobinemia (expressed in g per 100 mL), and on (ii) prothrombin level (expressed in %), at 48 hours; (iii) Need for blood transfusion with hemoglobin loss of more than 2 points within 48 hours of hypothermia (expressed in number of blood transfusion) (iv) Bleeding manifestations within 48 hours with or without need for surgical treatment; For cardiac risk: (i) percentage of patients with symptomatic cardiac rhythm disturbance requiring specific treatment between H0 and H24 and between H0 and H48 (expressed in percentage), (ii) total duration of vasopressors administered at H24 and at H48 (expressed in days)
    Time Frame
    Measurement following inclusion with a time maximal of 28 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Thomas KLEIN, MD
    Phone
    +33383154045
    Email
    t.klein@chru-nancy.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    ludivine ODOUL, Proj man
    Phone
    +33383155580
    Email
    l.odoul@chru-nancy.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bruno LEVY, PhD
    Organizational Affiliation
    CHRU NANCY, Nancy, France
    Official's Role
    Study Director
    First Name & Middle Initial & Last Name & Degree
    Nathalie THILLY, PhD
    Organizational Affiliation
    CHRU NANCY, Nancy, France
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Thomas KLEIN, MD
    Organizational Affiliation
    CHRU NANCY, Nancy, France
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    25923575
    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.
    Results Reference
    result
    PubMed Identifier
    25447805
    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.
    Results Reference
    result
    PubMed Identifier
    23584469
    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.
    Results Reference
    result

    Learn more about this trial

    Effects of Induced Moderate Hypothermia on ARDS Patients Under Venovenous ExtraCorporeal Membrane Oxygenation

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