Enhanced Lung Protective Ventilation With ECCO2R During ARDS

NCT ID: NCT03525691

Last Updated: 2023-12-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-23
• Study Completion Date: 2023-12-05

Brief 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 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:

1. Minimal distension: Tidal volume 4 ml/kg PBW and positive end-expiratory pressure (PEEP) based on the ARDSNet PEEP/FiO2 table (ARMA).

2. Maximal recruitment: 4 ml/kg PBW and PEEP adjusted to maintain a plateau pressure between 23 - 25 cmH2O.

3. Standard: Tidal volume 6 ml/kg and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA).

Conditions

ARDS, Human; Ventilator-Induced Lung Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Minimal distension

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)

Group Type: EXPERIMENTAL

Low flow Extracorporeal CO2 removal

Intervention Type: DEVICE

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)

Maximal recruitment

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)

Group Type: EXPERIMENTAL

Low flow Extracorporeal CO2 removal

Intervention Type: DEVICE

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)

Standard

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)

Group Type: ACTIVE_COMPARATOR

Low flow Extracorporeal CO2 removal

Intervention Type: DEVICE

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)

Interventions

Low flow Extracorporeal CO2 removal

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)

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• ARDS moderate or severe (Berlin criteria)
• Onset < 48 h
• Driving pressure ≥ 11 cmH2O

Exclusion Criteria

• 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
• Heparin allergy
• Contraindication to jugular vein catheterization
• Intracranial Hypertension

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hôpital Européen Marseille

OTHER

Sponsor Role: lead

Responsible Party

Jerome Allardet-Servent, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jérôme ALLARDET-SERVENT, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Européen Marseille

Locations

Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE

Marseille, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 26903337 (View on PubMed)

Amato 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.

Reference Type: RESULT

PMID: 25693014 (View on PubMed)

Allardet-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.

Reference Type: RESULT

PMID: 26488219 (View on PubMed)

Other Identifiers

2017-A03647-46

Identifier Type: -

Identifier Source: org_study_id