ARDSPRONECMONCT04607551
PRONing to Facilitate Weaning From ECMO in Patients With Refractory Acute Respiratory Distress Syndrome
A study testing Prone positionning and Supine position in people with ARDS, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
ECMO has emerged as a promising intervention that may provide more efficacious supportive care to patients with refractory severe acute respiratory distress syndrome (ARDS). The largest randomized trial of ECMO for severe forms of ARDS was recently published and demonstrated no significant benefit from early… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ARDS
- What is being tested?
- Prone positionning and Supine position
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteFrance
- Study dates
- 3 Mar 2021to 31 Dec 2022
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Severe ARDS refractory to conventional therapy placed on VV-ECMO support in the preceding 48h.
- Obtain informed consent from a close relative or surrogate. According to the specifications of emergency consent, randomization without the close relative or surrogate consent could be performed.
- Close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.
- Social security registration
Who cannot join
- Age <18 and >75
- Pregnancy and breastfeeding woman
- Initiation of VV-ECMO >48 h
- Resuscitation >10 minutes before ECMO
- Irreversible neurological pathology
- End-stage chronic lung disease
Show all 14Show fewer
- ARDS secondary to an abdominal surgery
- Contraindications for PP
- Irreversible ARDS with no hope for lung function recovery
- Patient moribund on the day of randomization, SAPS II >90
- Liver cirrhosis (Child B or C)
- Chronic renal failure requiring hemodialysis
- Lung transplantation
- Burns on more than 20 % of the body surface
Trial locations and contacts
1 site in 1 country.
About this study
ECMO has emerged as a promising intervention that may provide more efficacious supportive care to patients with refractory severe acute respiratory distress syndrome (ARDS). The largest randomized trial of ECMO for severe forms of ARDS was recently published and demonstrated no significant benefit from early initiation of ECMO with respect to 60-day mortality, when compared with a strategy of conventional mechanical ventilation (MV) (ref EOLIA). However, a rescue ECMO option was used by 28% of the controls, which is likely to have diluted the potential positive effect of ECMO. One may argue that a less restrictive primary endpoint, such as death or rescue ECMO, would have yielded positive findings.
Meanwhile, improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARDS. VV-ECMO can be used as a life-saving rescue therapy in patients with ARDS when MV cannot maintain adequate oxygenation or CO2 elimination. Alternatively, VV-ECMO may be used in patients who remain hypoxemic during MV (i.e., PaO2/FiO2<80 mmHg) despite optimization of MV (including the application of high levels of positive end-expiratory pressure (PEEP), neuromuscular blockers, and prone positioning) and allow "lung rest" by lowering airway pressures and tidal volume to ameliorate ventilator-induced lung injury (VILI).
Read more
Prone positioning (PP) has been used for more than 30 years in patients with acute hypoxemic respiratory failure and in particular with ARDS. Initially, PP in ARDS patients was proposed as an efficient mean to improve oxygenation, sometimes dramatically, in a large number of patients. In addition, it is now clear, and data are still accumulating, that PP is also able to prevent VILI which is as important as maintaining safe gas exchange in mechanical ventilation. Therefore, PP is a strategy that covers the two major goals of ventilator support in ARDS patients, maintaining safe oxygenation and preventing VILI and reducing mortality at the end. This latter objective makes sense on ECMO as one of the main objective of this device is to markedly reduce VILI by resting the lung.
Considering that PP is a valuable and safe therapy to reduce VILI, its combination with ECMO could enhance VILI prevention. In recent preliminary studies, it was reported that the combination of VV-ECMO and PP was associated with a dramatic improvement in oxygenation, in pulmonary and thoracic compliance and in chest X-ray findings. It may thus facilitate the weaning of ECMO and can be performed without compromising the safety of the patients. Lung recruitment and improvement in ventilation/perfusion mismatch on prone position may both contribute to improve oxygenation. PP may therefore be efficient to hasten the weaning of VV-ECMO when atelectasis and ventilation/perfusion mismatch occur under ultra-protective ventilation even in patients in whom pre-ECMO PP failed. In addition, it could also enhance ventilator induced lung injury prevention on ECMO.
- Conditions
- ARDS
- Being tested
- Prone positionning, Supine position
- Keywords
- ECMO Weaning, PRONING
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prone positionningProcedure or surgery
4 to 5 persons required for the procedure, one of them being dedicated to the management of the head of the patient, the endotracheal tube, the jugular ECMO cannula and the ventilator lines and another dedicated to the femoral ECMO cannula. The person at the head of the bed will coordinate the steps. The other persons will stand at each side of the bed. The direction of the rotation will be decided giving priority to the side of the central venous lines. The length of vascular and ventilator lines will be checked for appropriateness, the endotracheal tube and gastric tube will be secured, and the patient's knees, forehead, chest, and iliac crests will be protected using adhesive pads. The patient will be then moved along the horizontal plane to the opposite side of the bed selected for the direction of rotation. Patients will be proned at least four times during the first days on ECMO. Each prone session will stand for at least 16 hours
Supine positionProcedure or surgery
Patients assigned to supine will remain in a semi-recumbent position.
| Study group | Role | What they receive |
|---|---|---|
| Prone positionning | Experimental | Not described Receives: Procedure: Prone positionning |
| Supine position | Active comparator | Not described Receives: Procedure: Supine position |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to successful ECMO weaning within the 60 days following randomization
ECMO weaning will be considered successful only if the patient survives without ECMO, or lung transplantation 30 days after ECMO removal. Thus all ECMO weaning from randomization to 60 days after randomization will be considered, and the qualification for successful ECMO weaning will need 30 days of follow-up after ECMO removal (thus until day 90 after randomization for an ECMO weaning performed on day 60 after randomization).
Patients still under ECMO 60 days after randomization will be censored.
A protocolized management regarding weaning of VV-ECMO will be applied to both groups
The planned analysis will model the risk of successful ECMO ablation in the presence of competing risk (death and weaning failure).
Measured: Day 60
Secondary outcomes (18)
Mortality
Measured: Day 7, Day 14, Day 30, Day 60, Day 90
Total duration of ECMO support
Measured: Between inclusion visit (day 1) and day 60, Between inclusion visit and day 90,
Number of ECMO-free days
Measured: Between day 1 and Day 60/Day 90
Duration of ICU stay
Measured: Between day 1 and Day 60/Day 90
Duration of hospitalization
Measured: Between day 1 and Day 60/Day 90
Time to improvement in respiratory respiratory system compliance
Measured: Through study completion
Time to get a respiratory system compliance > 30 mL/cmH2O
Measured: Between day 1 and Day 60/Day 90
Number of days with organ failure
defined by SOFA score
Measured: Between day 1 and Day 60
Number of days alive without organ failure
defined by SOFA score
Measured: Between day 1 and Day 60
Number of ventilator assist pneumonia, bacteriemia, and cannula infection episodes
Measured: Through study completion
Number of days with hemodynamic support with catecholamines
Measured: Between day 1 and Day 60
Number of days alive without hemodynamic support with catecholamines
Measured: Between day 1 and Day 60
Number of days with mechanical ventilation
Measured: Between day 1 and Day 60
Number of days alive without mechanical ventilation
Measured: Between day 1 and Day 60
Acute core pulmonale diagnosis
by echocardiography
Measured: Between day 1 and D60
Need for VA ECMO
Measured: Between day 1 and Day 60/Day 90
Incidence of intervention side effects
(accidental decannulation, non-scheduled extubation during the procedure, hemoptysis, endotracheal tube obstruction, cardiac arrest, pressure sore, and death
Measured: Between day 1 and Day 60
Occurrence of refractory hypoxemia on ECMO
Measured: Through study completion, an average of 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start3 Mar 2021
- Primary completion7 Mar 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ARDSStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04607551
- Sponsor's protocol ID
- APHP180607
- Other IDs
- 2019-A02669-48
- Acronym
- PRONECMO
- Status last verified
- Jun 2022
- First submitted
- 28 Sep 2020
- Last updated
- 1 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Schmidt M, Hajage D, Lebreton G, Dres M, Guervilly C, Richard JC, Sonneville R, Winiszewski H, Muller G, Beduneau G, Mercier E, Roze H, Lesouhaitier M, Terzi N, Thille AW, Laurent I, Kimmoun A, Combes A; PRONECMO Investigators, the REVA Network, and the International ECMO Network (ECMONet). Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial. JAMA. 2023 Dec 26;330(24):2343-2353. doi: 10.1001/jama.2023.24491.
PubMed 38038395
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRONing to Facilitate Weaning From ECMO in Patients With Refractory Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT04607551
- Acronym / sponsor ID
- PRONECMO / APHP180607
- Conditions
- ARDS
- Keywords
- ECMO Weaning, PRONING
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 3 Mar 2021 (actual)
- Primary completion
- 7 Mar 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 29 Oct 2020 (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.
ECMO has emerged as a promising intervention that may provide more efficacious supportive care to patients with refractory severe acute respiratory distress syndrome (ARDS). The largest randomized trial of ECMO for severe forms of ARDS was recently published and demonstrated no significant benefit from early initiation of ECMO with respect to 60-day mortality, when compared with a strategy of conventional mechanical ventilation (MV) (ref EOLIA). However, a rescue ECMO option was used by 28% of the controls, which is likely to have diluted the potential positive effect of ECMO. One may argue that a less restrictive primary endpoint, such as death or rescue ECMO, would have yielded positive findings.
Meanwhile, improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARDS. VV-ECMO can be used as a life-saving rescue therapy in patients with ARDS when MV cannot maintain adequate oxygenation or CO2 elimination. Alternatively, VV-ECMO may be used in patients who remain hypoxemic during MV (i.e., PaO2/FiO2<80 mmHg) despite optimization of MV (including the application of high levels of positive end-expiratory pressure (PEEP), neuromuscular blockers, and prone positioning) and allow "lung rest" by lowering airway pressures and tidal volume to ameliorate ventilator-induced lung injury (VILI).
Prone positioning (PP) has been used for more than 30 years in patients with acute hypoxemic respiratory failure and in particular with ARDS. Initially, PP in ARDS patients was proposed as an efficient mean to improve oxygenation, sometimes dramatically, in a large number of patients. In addition, it is now clear, and data are still accumulating, that PP is also able to prevent VILI which is as important as maintaining safe gas exchange in mechanical ventilation. Therefore, PP is a strategy that covers the two major goals of ventilator support in ARDS patients, maintaining safe oxygenation and preventing VILI and reducing mortality at the end. This latter objective makes sense on ECMO as one of the main objective of this device is to markedly reduce VILI by resting the lung.
Considering that PP is a valuable and safe therapy to reduce VILI, its combination with ECMO could enhance VILI prevention. In recent preliminary studies, it was reported that the combination of VV-ECMO and PP was associated with a dramatic improvement in oxygenation, in pulmonary and thoracic compliance and in chest X-ray findings. It may thus facilitate the weaning of ECMO and can be performed without compromising the safety of the patients. Lung recruitment and improvement in ventilation/perfusion mismatch on prone position may both contribute to improve oxygenation. PP may therefore be efficient to hasten the weaning of VV-ECMO when atelectasis and ventilation/perfusion mismatch occur under ultra-protective ventilation even in patients in whom pre-ECMO PP failed. In addition, it could also enhance ventilator induced lung injury prevention on ECMO.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prone positionning | Experimental | Procedure: Prone positionning |
| Supine position | Active comparator | Procedure: Supine position |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Severe ARDS refractory to conventional therapy placed on VV-ECMO support in the preceding 48h.
- Obtain informed consent from a close relative or surrogate. According to the specifications of emergency consent, randomization without the close relative or surrogate consent could be performed.
- Close relative/surrogate/family consent will be asked as soon as possible. The patient will be asked to give his/her consent for the continuation of the trial when his/her condition will allow.
- Social security registration
Key exclusion criteria (14 listed)
- Age <18 and >75
- Pregnancy and breastfeeding woman
- Initiation of VV-ECMO >48 h
- Resuscitation >10 minutes before ECMO
- Irreversible neurological pathology
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 |
|---|---|---|
| Prone positionning4 to 5 persons required for the procedure, one of them being dedicated to the management of the head of the patient, the endotracheal tube, the jugular ECMO cannula and the ventilator lines and another dedicated to the femoral ECMO cannula. The person at the head of the bed will coordinate the steps. The other persons will stand at each side of the bed. The direction of the rotation will be decided giving priority to the side of the central venous lines. The length of vascular and ventilator lines will be checked for appropriateness, the endotracheal tube and gastric tube will be secured, and the patient's knees, forehead, chest, and iliac crests will be protected using adhesive pads. The patient will be then moved along the horizontal plane to the opposite side of the bed selected for the direction of rotation. Patients will be proned at least four times during the first days on ECMO. Each prone session will stand for at least 16 hours | Procedure or surgery | Prone positionning |
| Supine positionPatients assigned to supine will remain in a semi-recumbent position. | Procedure or surgery | Supine position |
Primary outcome
Time to successful ECMO weaning within the 60 days following randomization
Time frame: Day 60
ECMO weaning will be considered successful only if the patient survives without ECMO, or lung transplantation 30 days after ECMO removal. Thus all ECMO weaning from randomization to 60 days after randomization will be considered, and the qualification for successful ECMO weaning will need 30 days of follow-up after ECMO removal (thus until day 90 after randomization for an ECMO weaning performed on day 60 after randomization). Patients still under ECMO 60 days after randomization will be censored. A protocolized management regarding weaning of VV-ECMO will be applied to both groups The planned analysis will model the risk of successful ECMO ablation in the presence of competing risk (death and weaning failure).
18 secondary outcomes
Mortality
Time frame: Day 7, Day 14, Day 30, Day 60, Day 90
Total duration of ECMO support
Time frame: Between inclusion visit (day 1) and day 60, Between inclusion visit and day 90,
Number of ECMO-free days
Time frame: Between day 1 and Day 60/Day 90
Duration of ICU stay
Time frame: Between day 1 and Day 60/Day 90
Duration of hospitalization
Time frame: Between day 1 and Day 60/Day 90
Time to improvement in respiratory respiratory system compliance
Time frame: Through study completion
Time to get a respiratory system compliance > 30 mL/cmH2O
Time frame: Between day 1 and Day 60/Day 90
Number of days with organ failure
Time frame: Between day 1 and Day 60
Number of days alive without organ failure
Time frame: Between day 1 and Day 60
Number of ventilator assist pneumonia, bacteriemia, and cannula infection episodes
Time frame: Through study completion
Number of days with hemodynamic support with catecholamines
Time frame: Between day 1 and Day 60
Number of days alive without hemodynamic support with catecholamines
Time frame: Between day 1 and Day 60
Number of days with mechanical ventilation
Time frame: Between day 1 and Day 60
Number of days alive without mechanical ventilation
Time frame: Between day 1 and Day 60
Acute core pulmonale diagnosis
Time frame: Between day 1 and D60
Need for VA ECMO
Time frame: Between day 1 and Day 60/Day 90
Incidence of intervention side effects
Time frame: Between day 1 and Day 60
Occurrence of refractory hypoxemia on ECMO
Time frame: Through study completion, an average of 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Derived from this study: PubMed 38038395Schmidt M, Hajage D, Lebreton G, Dres M, Guervilly C, Richard JC, Sonneville R, Winiszewski H, Muller G, Beduneau G, Mercier E, Roze H, Lesouhaitier M, Terzi N, Thille AW, Laurent I, Kimmoun A, Combes A; PRONECMO Investigators, the REVA Network, and the International ECMO Network (ECMONet). Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial. JAMA. 2023 Dec 26;330(24):2343-2353. doi: 10.1001/jama.2023.24491.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prone positionning and Supine position in people with ARDS, run by Assistance Publique - Hôpitaux de Paris at 1 site in 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 14 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: finished, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to successful ECMO weaning within the 60 days following randomization (time frame: Day 60). 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 NCT04607551, which also lists 1 linked publication.
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 Mar 2023.