ARDS, HumanPROVENCT03525691
Enhanced Lung Protective Ventilation With ECCO2R During ARDS
A study testing Low flow Extracorporeal CO2 removal in people with ARDS, Human and Ventilator-Induced Lung Injury, run by Hôpital Européen Marseille at 1 site in France.
Trial summary
Acute Respiratory Distress Syndrome (ARDS) is associated with a mortality rate of 30 - 45 % and required invasive mechanical ventilation (MV) in almost 85 % of patients[1]. During controlled MV, driving pressure (i.e., the difference between end-inspiratory and end-expiratory airway pressure) depends of both tidal… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS, Human, Ventilator-Induced Lung Injury
- What is being tested?
- Low flow Extracorporeal CO2 removal
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteFrance
- Study dates
- 23 May 2018to 5 Dec 2023
- 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
- ARDS moderate or severe (Berlin criteria)
- Onset < 48 h
- Driving pressure ≥ 11 cmH2O
Who cannot join
- Lack of consent or social protection
- Chronic respiratory failure (requiring Oxygen or NIPPV)
- Severe hypoxemia: PaO2/FIO2 < 80 with PEEP ≥ 18 cmH2O AND FIO2= 1
- Acute Renal Failure requiring RRT
- DNR order or death expected within the next 72 hours
- Planned surgery or transport out-of-ICU expected within the next 72 hours
Show all 9Show fewer
- Heparin allergy
- Contraindication to jugular vein catheterization
- Intracranial Hypertension
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome (ARDS) is associated with a mortality rate of 30 - 45 % and required invasive mechanical ventilation (MV) in almost 85 % of patients[1]. During controlled MV, driving pressure (i.e., the difference between end-inspiratory and end-expiratory airway pressure) depends of both tidal volume and respiratory system compliance. Either excessive tidal volume or reduced lung aeration may increase the driving pressure. ARDS patients receiving tidal volume of 6 ml/kg predicted body weight (PBW) and having a day-1 driving pressure ≥ 14 cmH2O have an increased risk of death in the hospital[2]. Seemly, in the LUNG SAFE observational cohort, ARDS patients having a day-1 driving pressure < 11 cmH2O had the lowest risk of death in the hospital[1]. Hence, driving pressure acts as a major contributor of mortality in ARDS, and probably reflects excessive regional lung distension resulting in pro-inflammatory and fibrotic biological processes. Whether decreasing the driving pressure by an intervention change mortality remains an hypothesis; but one of means is to decrease the tidal volume from 6 to 4 ml/ kg predicted body weight (PBW). However, this strategy promotes hypercarbia, at constant respiratory rate, by decreasing the alveolar ventilation. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy prevents from hypercarbia. A number of low-flow ECCO2R devices are now available and some of those use renal replacement therapy (RRT) platform. The investigators previously reported that combining a membrane oxygenator (0.65 m²) within a hemofiltration circuit provides efficacious low flow ECCO2R and blood purification in patients presenting with both ARDS and Acute Kidney injury[3].
This study aims to investigate the efficacy of an original ECCO2R system combining a 0.67 m² membrane oxygenator (Lilliput 2, SORIN) inserted within a specific circuit (HP-X, BAXTER) and mounted on a RRT monitor (PrismafleX, BAXTER). Such a therapy only aims to provide decarboxylation but not blood purification and has the huge advantage to be potentially implemented in most ICUs without requiring a specific ECCO2R device. The study will consist in three periods:
Read more
- The first period will address the efficacy of this original ECCO2R system at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design.
- The second part will investigate the effect of varying the sweep gas flow (0-2-4-6-8-10 l/min) and the mixture of the sweep gas (Air/O2) on the CO2 removal rate.
- The third part will compare three ventilatory strategies applied in a crossover design:
- Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).
- Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O.
- Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA).
- Conditions
- ARDS, Human, Ventilator-Induced Lung Injury
- Being tested
- Low flow Extracorporeal CO2 removal
- Medical subject headings
- Respiratory Distress Syndrome, Ventilator-Induced Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low flow Extracorporeal CO2 removalDevice
Low flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX)
| Study group | Role | What they receive |
|---|---|---|
| Minimal distension | Experimental | Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) Receives: Device: Low flow Extracorporeal CO2 removal |
| Maximal recruitment | Experimental | Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) Receives: Device: Low flow Extracorporeal CO2 removal |
| Standard | Active comparator | Tidal volume 6 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R (no sweep gas flow, blood flow = 400 mL/min) Receives: Device: Low flow Extracorporeal CO2 removal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PaCO2
20 % decrease in PaCO2 after initiation of ECCO2R at tidal volume of 4 ml/kg PBW (as compared to 4 ml/kg without ECCO2R)
Measured: 15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.
Secondary outcomes (9)
PaCO2
Arterial blood gas analyser (RAPIDPoint 500)
Measured: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
CO2 removal rate
Using measurements from both the blood side and the gas side (two methods)
Measured: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Transpulmonary pressure and work of breathing
Using an oesophageal balloon catheter (NutriVent catheter) and a dedicated monitor (FluxMed, MBMed)
Measured: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Regional tidal ventilation
Using an Electrical Impedance Tomography device (BB², Swisstom)
Measured: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
End-expiratory Lung Volume
Using the nitrogen wash-in wash-out method (Engstrom GE)
Measured: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Plasma Cytokines
Using Elisa custom kit (Qiagen) from plasma samples
Measured: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Pulmonary Cytokines
Using Elisa custom kit (Qiagen) from BAL samples
Measured: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Type III Procollagen
Using both RIA and Elisa methods from plasma and BAL samples
Measured: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Pulmonary Inflammatory and Fibrotic pathway
Using mRNA custom kit RT-PCR analysis (Qiagen) from BAL samples
Measured: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start23 May 2018
- Primary completion5 Dec 2023
- Study completion5 Dec 2023
Why it stopped: insufficient enrollment
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.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hôpital Européen Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jerome Allardet-Servent, MD, Hôpital Européen Marseille
- Investigators
- Jérôme ALLARDET-SERVENT, MD, Principal investigator, Hopital Européen Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525691
- Sponsor's protocol ID
- 2017-A03647-46
- Acronym
- PROVE
- Status last verified
- Dec 2023
- First submitted
- 3 May 2018
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.
PubMed 25693014Allardet-Servent J, Castanier M, Signouret T, Soundaravelou R, Lepidi A, Seghboyan JM. Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study. Crit Care Med. 2015 Dec;43(12):2570-81. doi: 10.1097/CCM.0000000000001296.
PubMed 26488219
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT03525691
- Acronym / sponsor ID
- PROVE / 2017-A03647-46
- Conditions
- ARDS, Human, Ventilator-Induced Lung Injury
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Hôpital Européen MarseilleUniversity, hospital or other
- Study start
- 23 May 2018 (actual)
- Primary completion
- 5 Dec 2023 (actual)
- Study completion
- 5 Dec 2023 (actual)
- First posted
- 16 May 2018 (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 associated with a mortality rate of 30 - 45 % and required invasive mechanical ventilation (MV) in almost 85 % of patients[1]. During controlled MV, driving pressure (i.e., the difference between end-inspiratory and end-expiratory airway pressure) depends of both tidal volume and respiratory system compliance. Either excessive tidal volume or reduced lung aeration may increase the driving pressure. ARDS patients receiving tidal volume of 6 ml/kg predicted body weight (PBW) and having a day-1 driving pressure ≥ 14 cmH2O have an increased risk of death in the hospital[2]. Seemly, in the LUNG SAFE observational cohort, ARDS patients having a day-1 driving pressure < 11 cmH2O had the lowest risk of death in the hospital[1]. Hence, driving pressure acts as a major contributor of mortality in ARDS, and probably reflects excessive regional lung distension resulting in pro-inflammatory and fibrotic biological processes. Whether decreasing the driving pressure by an intervention change mortality remains an hypothesis; but one of means is to decrease the tidal volume from 6 to 4 ml/ kg predicted body weight (PBW). However, this strategy promotes hypercarbia, at constant respiratory rate, by decreasing the alveolar ventilation. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy prevents from hypercarbia. A number of low-flow ECCO2R devices are now available and some of those use renal replacement therapy (RRT) platform. The investigators previously reported that combining a membrane oxygenator (0.65 m²) within a hemofiltration circuit provides efficacious low flow ECCO2R and blood purification in patients presenting with both ARDS and Acute Kidney injury[3].
This study aims to investigate the efficacy of an original ECCO2R system combining a 0.67 m² membrane oxygenator (Lilliput 2, SORIN) inserted within a specific circuit (HP-X, BAXTER) and mounted on a RRT monitor (PrismafleX, BAXTER). Such a therapy only aims to provide decarboxylation but not blood purification and has the huge advantage to be potentially implemented in most ICUs without requiring a specific ECCO2R device. The study will consist in three periods:
- The first period will address the efficacy of this original ECCO2R system at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design.
- The second part will investigate the effect of varying the sweep gas flow (0-2-4-6-8-10 l/min) and the mixture of the sweep gas (Air/O2) on the CO2 removal rate.
- The third part will compare three ventilatory strategies applied in a crossover design:
- Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).
- Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O.
- Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA).
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Minimal distension | Experimental | Device: Low flow Extracorporeal CO2 removalTidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) |
| Maximal recruitment | Experimental | Device: Low flow Extracorporeal CO2 removalTidal volume 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O + ECCO2R (sweep gas = 8 L/min, blood flow = 400 mL/min) |
| Standard | Active comparator | Device: Low flow Extracorporeal CO2 removalTidal volume 6 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R (no sweep gas flow, blood flow = 400 mL/min) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ARDS moderate or severe (Berlin criteria)
- Onset < 48 h
- Driving pressure ≥ 11 cmH2O
Key exclusion criteria (9 listed)
- Lack of consent or social protection
- Chronic respiratory failure (requiring Oxygen or NIPPV)
- Severe hypoxemia: PaO2/FIO2 < 80 with PEEP ≥ 18 cmH2O AND FIO2= 1
- Acute Renal Failure requiring RRT
- DNR order or death expected within the next 72 hours
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 |
|---|---|---|
| Low flow Extracorporeal CO2 removalLow flow Extracorporeal CO2 removal using a 0.67 m² membrane oxygenator (Lilliput 2) and a specific circuit (HP-X) mounted on a RRT monitor (PrismafleX) | Device | Maximal recruitment, Minimal distension, Standard |
Primary outcome
Change in PaCO2
Time frame: 15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.
20 % decrease in PaCO2 after initiation of ECCO2R at tidal volume of 4 ml/kg PBW (as compared to 4 ml/kg without ECCO2R)
9 secondary outcomes
PaCO2
Time frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
CO2 removal rate
Time frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Transpulmonary pressure and work of breathing
Time frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Regional tidal ventilation
Time frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
End-expiratory Lung Volume
Time frame: each 15 minutes up to the third hour (Part I and II of the study). In the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Plasma Cytokines
Time frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Pulmonary Cytokines
Time frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Type III Procollagen
Time frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Pulmonary Inflammatory and Fibrotic pathway
Time frame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Results and safety
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Results publication: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Results publication: PubMed 25693014Amato MB, Meade MO, Slutsky AS, Brochard L, Costa EL, Schoenfeld DA, Stewart TE, Briel M, Talmor D, Mercat A, Richard JC, Carvalho CR, Brower RG. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.
- Results publication: PubMed 26488219Allardet-Servent J, Castanier M, Signouret T, Soundaravelou R, Lepidi A, Seghboyan JM. Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study. Crit Care Med. 2015 Dec;43(12):2570-81. doi: 10.1097/CCM.0000000000001296.
- 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.
Jérôme ALLARDET-SERVENT, MD principal investigator
Hopital Européen Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low flow Extracorporeal CO2 removal in people with ARDS, Human and Ventilator-Induced Lung Injury, run by Hôpital Européen Marseille 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 3 inclusion and 9 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: stopped early, as of the sponsor's last update on 12 Dec 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 was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
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?
Change in PaCO2 (time frame: 15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.). 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 NCT03525691, 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 12 Dec 2023; AzTrials last refreshed its copy on 26 Oct 2026.