Enhanced Lung Protective Ventilation With ECCO2R During ARDS

NCT03525691 | Terminated

• 1 other identifier: 2017-A03647-46
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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:
• 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

Outcome Measures

Primary Outcomes (1)

• 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)

  15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.

Secondary Outcomes (9)

• PaCO2

  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

  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

  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

  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

  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.

Other Outcomes (5)

• Plasma Free Hemoglobin

  every 24 hours, up to 72 hours.

• Haptoglobin

  every 24 hours, up to 72 hours.

• Lacticodéshydrogenase (LDH)

  every 24 hours, up to 72 hours.

Study Arms (3)

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)

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)

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)

Device: Low flow Extracorporeal CO2 removal

Interventions

Low flow Extracorporeal CO2 removal 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; Minimal distension; Standard

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hôpital Européen Marseille: lead

Study Sites (1)

Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE

Marseille, France

Location

Related Publications (3)

• 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.

  PMID: 26903337 RESULT

• 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.

  PMID: 25693014 RESULT

• 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.

  PMID: 26488219 RESULT

MeSH Terms

Conditions

Respiratory Distress Syndrome; Ventilator-Induced Lung Injury

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury

Study Officials

• Jérôme ALLARDET-SERVENT, MD

  Hopital Européen Marseille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 16, 2018
• Study Start: May 23, 2018
• Primary Completion: December 5, 2023
• Study Completion: December 5, 2023
• Last Updated: December 12, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)