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
About this trial
This is an interventional treatment trial for ARDS, Human focused on measuring Hypothermia, ECMO, Refractory hypoxemia
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
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
NCT ID
NCT05306392
First Posted
February 16, 2022
Last Updated
March 23, 2022
Sponsor
Central Hospital, Nancy, France
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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