ARDS, HumanHypoLungECMONCT05306392
Effects of Induced Moderate Hypothermia on ARDS Patients Under Venovenous ExtraCorporeal Membrane Oxygenation
A study testing Moderate Hypothermia and Normothermia in people with ARDS, Human and Extracorporeal Membrane Oxygenation Complication, run by Central Hospital, Nancy, France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS, Human, Extracorporeal Membrane Oxygenation Complication, Hypothermia
- What is being tested?
- Moderate Hypothermia and Normothermia
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Sep 2022to Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Evaluation of the Effectiveness of Induced Moderate Hypothermia in the Management of Patients With Severe ARDS Under Venovenous ECMO
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.
Read more
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.
Read the 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.
- Being tested
- Moderate Hypothermia, Normothermia
- Keywords
- Hypothermia, ECMO, Refractory hypoxemia
- Medical subject headings
- Respiratory Distress Syndrome, Hypothermia, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moderate HypothermiaDevice
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.
NormothermiaDevice
Temperature at 36°C will be maintained during 48 hours after having reached 36 °C
| Study group | Role | What they receive |
|---|---|---|
| Moderate Hypothermia | Experimental | 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 Receives: Device: Moderate Hypothermia |
| Control - Normothermia | Sham comparator | 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 Receives: Device: Normothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 %)
Measured: between initiation of hypothermia and 48 hours of induced hypothermia
Secondary outcomes (8)
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 %)
Measured: at 1 hour, 6 hours, 24 hours of the randomization
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)
Measured: Evaluation of arterial transport of oxygen by peripheral gas measurement at 1 hour, 6 hours, 24 hours and 48 hours of hypothermia
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)
Measured: Measurement at 1 hour, 6 hours, 24 hours and 48 hours
Survival of patients hospitalized in intensive care
The percentage of patients who died during resuscitation hospitalization
Measured: Measurement following inclusion with a time maximal of 28 days
The duration of VV ECMO during hospitalization in the intensive care unit
The duration of VV ECMO (in days) during resuscitation hospitalization,
Measured: Measurement following inclusion with a time maximal of 28 days
The number of days without mechanical ventilation during resuscitation hospitalization
The number of days without invasive mechanical ventilation during resuscitation hospitalization
Measured: Measurement following inclusion with a time maximal of 28 days
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)
Measured: at 24 and 48 hours
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)
Measured: Measurement following inclusion with a time maximal of 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study startSep 2022 (estimated)
- Primary completionMar 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ARDS, HumanStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Klein Thomas, Central Hospital, Nancy, France
- Investigators
- Bruno LEVY, PhD, Study director, CHRU NANCY, Nancy, FranceNathalie THILLY, PhD, Study chair, CHRU NANCY, Nancy, FranceThomas KLEIN, MD, Study chair, CHRU NANCY, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306392
- Sponsor's protocol ID
- 2022-A00168-35
- Acronym
- HypoLungECMO
- Status last verified
- Feb 2022
- First submitted
- 16 Feb 2022
- Last updated
- 1 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25923575Levy 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.
PubMed 25447805Kimmoun 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.
PubMed 23584469
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effectiveness of Induced Moderate Hypothermia in the Management of Patients With Severe ARDS Under Venovenous ECMO
- ClinicalTrials.gov ID
- NCT05306392
- Acronym / sponsor ID
- HypoLungECMO / 2022-A00168-35
- Keywords
- Hypothermia, ECMO, Refractory hypoxemia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- Sep 2022 (estimated)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 1 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Monocentric controlled study, with randomization in two groups (induced hypothermia group and control group), at the Nancy Hospital - Intensive care Unit
| Arm | Type | Receives |
|---|---|---|
| Moderate Hypothermia | Experimental | Device: Moderate HypothermiaPatients 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 |
| Control - Normothermia | Sham comparator | Device: NormothermiaPatients with acute respiratory distress syndrome treated with venovenous ECMO to a strategy of normothermia (36°C≤ T°C ≤37°C) associated with usual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Moderate Hypothermiamoderate 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. | Device | Moderate Hypothermia |
| NormothermiaTemperature at 36°C will be maintained during 48 hours after having reached 36 °C | Device | Control - Normothermia |
Primary outcome
Effectiveness of 48 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
Time frame: between initiation of hypothermia and 48 hours of induced hypothermia
Hypoxemia is measured by arterial saturation of oxygen (expressed in %)
8 secondary outcomes
Effectiveness of 1 hours, 6 hours, 24 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO
Time frame: at 1 hour, 6 hours, 24 hours of the randomization
Evolution of arterial transport of oxygen during therapeutic hypothermia
Time frame: Evaluation of arterial transport of oxygen by peripheral gas measurement at 1 hour, 6 hours, 24 hours and 48 hours of hypothermia
Evolution of ECMO flow / cardiac output ratio (expressed in %)
Time frame: Measurement at 1 hour, 6 hours, 24 hours and 48 hours
Survival of patients hospitalized in intensive care
Time frame: Measurement following inclusion with a time maximal of 28 days
The duration of VV ECMO during hospitalization in the intensive care unit
Time frame: Measurement following inclusion with a time maximal of 28 days
The number of days without mechanical ventilation during resuscitation hospitalization
Time frame: Measurement following inclusion with a time maximal of 28 days
Microcirculatory perfusion and flow variables
Time frame: at 24 and 48 hours
The safety of induced hypothermia treatment during hospitalization in the intensive care unit (infections, coagulation disorders, cardiac risk).
Time frame: Measurement following inclusion with a time maximal of 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2022.
- Results publication: PubMed 25923575Montisci 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 publication: PubMed 25447805Levy 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 publication: PubMed 23584469Kimmoun 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno LEVY, PhD study director
CHRU NANCY, Nancy, France
Nathalie THILLY, PhD study chair
CHRU NANCY, Nancy, France
Thomas KLEIN, MD study chair
CHRU NANCY, Nancy, France
Questions about this trial
What is this clinical trial studying?
A study testing Moderate Hypothermia and Normothermia in people with ARDS, Human and Extracorporeal Membrane Oxygenation Complication, run by Central Hospital, Nancy, France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Thomas KLEIN, MD (+33383154045, t.klein@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of 48 hours therapeutic hypothermia on the evolution of hypoxemia in patients on VV ECMO (time frame: between initiation of hypothermia and 48 hours of induced hypothermia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05306392, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2022.