Enhanced Lung Protective Ventilation With ECCO2R During ARDS

ARDS, Human Clinical Trial

— PROVE  

Official title:

Enhanced Lung Protective Ventilation With Extracorporeal CO2 Removal During Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03525691
• Other study ID #: 2017-A03647-46
• Status: Terminated
• Phase: N/A
• Start date: May 23, 2018
• Est. completion date: December 5, 2023

Study information

• Verified date: December 2023
• Source: Hôpital Européen Marseille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 5, 2023
• Est. primary completion date: December 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ARDS, Human
• Lung Injury
• Respiratory Distress Syndrome
• Ventilator-Induced Lung Injury

Intervention

Device:
• 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)

Locations

Country	Name	City	State
France	Service de REANIMATION, HOPITAL EUROPEEN MARSEILLE	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Hôpital Européen Marseille

Country where clinical trial is conducted

France, 

References & Publications (3)

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: T — View 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):74 — View 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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma Free Hemoglobin	serum samples	every 24 hours, up to 72 hours.
Other	Haptoglobin	serum samples	every 24 hours, up to 72 hours.
Other	Lacticodéshydrogenase (LDH)	serum samples	every 24 hours, up to 72 hours.
Other	schizocytes	serum samples	every 24 hours, up to 72 hours.
Other	Bilirubin	serum samples	every 24 hours, up to 72 hours.
Primary	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	PaCO2	Arterial blood gas analyser (RAPIDPoint 500)	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.
Secondary	CO2 removal rate	Using measurements from both the blood side and the gas side (two methods)	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.
Secondary	Transpulmonary pressure and work of breathing	Using an oesophageal balloon catheter (NutriVent catheter) and a dedicated monitor (FluxMed, MBMed)	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.
Secondary	Regional tidal ventilation	Using an Electrical Impedance Tomography device (BB², Swisstom)	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.
Secondary	End-expiratory Lung Volume	Using the nitrogen wash-in wash-out method (Engstrom GE)	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.
Secondary	Plasma Cytokines	Using Elisa custom kit (Qiagen) from plasma samples	Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Secondary	Pulmonary Cytokines	Using Elisa custom kit (Qiagen) from BAL samples	Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Secondary	Type III Procollagen	Using both RIA and Elisa methods from plasma and BAL samples	Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.
Secondary	Pulmonary Inflammatory and Fibrotic pathway	Using mRNA custom kit RT-PCR analysis (Qiagen) from BAL samples	Only in the third part, measurement at baseline and at 1 hour and at 22 hours into each arm.