Clinical trial NCT03004885: Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung
Official title: Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Lead sponsor: Hôpital Européen Marseille
Sponsor class: OTHER
First posted: 2016-12-29
Enrollment: 1
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) still remains associated with a mortality rate of 30 - 45 % despite improvement in mechanical ventilation. Driving pressure, defined as the difference between the end-inspiratory and the end-expiratory airway pressure, appears as an important factor contributing to mortality in patients with the ARDS. In patients already receiving a conventional tidal volume of 6 ml/kg predicted body weight (PBW), a driving pressure ≥ 14 cmH2O increases the risk of death in the hospital. One mean to lower the driving pressure is to decrease the tidal volume such that from 6 to 4 ml/kg predicted body weight. However, this strategy promotes hypercarbia by reducing the alveolar ventilation, providing the respiratory rate is constant. In this setting, implementing an extracorporeal CO2 removal (ECCO2R) therapy may offset the associated hypercarbia. The investigators have previously demonstrated that combining a membrane oxygenator within an hemofiltration circuit provides efficacious low flow ECCO2R on a renal replacement therapy monitor. In this study, we thought to investigate the efficacy of the PrismaLung stand-alone therapy. Using a PrismaFlex monitor and a HP-X circuit, a neonatal membrane oxygenator (PrismaLung) is used to provide decarboxylation without renal replacement therapy. The study will consist in three periods:

* The first period will address the efficacy of the PrismaLung device at tidal volume of 6 and 4 ml/kg PBW using an off-on-off design.
* The second part of the study will investigate the effect of varying the sweep gas flow and the mixture of the sweep gas on the CO2 removal rate (random order).
* The third part will compare three ventilatory strategies applied in a cross-over 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).

Each strategies will be apply in a random order for a duration of 22 hours. Pulmonary inflammatory and fibrosis pathway will be assess before and after each period using bronchoalveolar lavage (BAL) samples. Systemic inflammatory cytokines will also be investigate. Main measurements will include respiratory mechanics, transpulmonary pressure, work of breathing, end-expiratory lung volume and tidal ventilation using electrical impedance tomography.


Eligibility criteria: Inclusion Criteria:

* ARDS moderate or severe (Berlin criteria)
* Onset \< 48 h
* Driving pressure ≥ 14 cmH2O

Exclusion Criteria:

* Lack of consent or social protection
* Chronic respiratory failure (requiring Oxygen or NIPPV)
* Severe hypoxemia: PaO2/FIO2 \< 100 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 out-of-ICU transportation expected within the next 72 hours
* Heparin allergy
* Contraindication to jugular vein catheterization
* Intracranial Hypertension

Primary outcomes:
measure: Change in PaCO2
timeFrame: 15 min after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW (during the first part of the study).
Secondary outcomes:
measure: PaCO2
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: CO2 removal rate
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Respiratory mechanics work of breathing
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Transpulmonary pressure
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Work of breathing
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: EIT
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: EELV
timeFrame: q15 min during part 1 and part 2 of the study. In the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Plasma Cytokines
timeFrame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Pulmonary Cytokines
timeFrame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Pulmonary Type III Procollagen
timeFrame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
measure: Pulmonary Inflammatory and Fibrotic pathway
timeFrame: Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Other outcomes:
measure: Plasma Free Hemoglobin
timeFrame: q24 h, up to 72 h
measure: Haptoglobin
timeFrame: q24 h, up to 72 h
measure: Lacticodéshydrogenase (LDH)
timeFrame: q24 h, up to 72 h
measure: schizocytes
timeFrame: q24 h, up to 72 h
measure: Bilirubin
timeFrame: q24 h, up to 72 h
Locations:
city: Marseille
country: France
facility: Hopital Europeen Marseille
Study officials:
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.