Clinical trial NCT03525691: Enhanced Lung Protective Ventilation With ECCO2R During ARDS
Official title: Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: ARDS, Human
Ventilator-Induced Lung Injury
Lead sponsor: Hôpital Européen Marseille
Sponsor class: OTHER
First posted: 2018-05-16
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

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).


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

Primary outcomes:
measure: Change in PaCO2
timeFrame: 15 minutes after initiation of ECCO2R at tidal volume of 4 ml/kg PBW.
Secondary outcomes:
measure: PaCO2
timeFrame: 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.
measure: CO2 removal rate
timeFrame: 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.
measure: Transpulmonary pressure and work of breathing
timeFrame: 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.
measure: Regional tidal ventilation
timeFrame: 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.
measure: End-expiratory Lung Volume
timeFrame: 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.
measure: Plasma Cytokines
timeFrame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
measure: Pulmonary Cytokines
timeFrame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
measure: Type III Procollagen
timeFrame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
measure: Pulmonary Inflammatory and Fibrotic pathway
timeFrame: Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Other outcomes:
measure: Plasma Free Hemoglobin
timeFrame: every 24 hours, up to 72 hours.
measure: Haptoglobin
timeFrame: every 24 hours, up to 72 hours.
measure: Lacticodéshydrogenase (LDH)
timeFrame: every 24 hours, up to 72 hours.
measure: schizocytes
timeFrame: every 24 hours, up to 72 hours.
measure: Bilirubin
timeFrame: every 24 hours, up to 72 hours.
Locations:
city: Marseille
country: France
facility: Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE
Study officials:
affiliation: Hopital Européen Marseille
name: Jérôme ALLARDET-SERVENT, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.