Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung (PROVAP)

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.

Study Overview

• Status: Terminated
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Device: PrismaLung

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Marseille, France
    • Hôpital Européen Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Minimal Distension; Tidal volume 4 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) + ECCO2R	Device: PrismaLung; Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator
EXPERIMENTAL: Maximal Recruitment; Tidal volume 4 ml/kg PBW and PEEP adjusted to maintain plateau pressure between 23 - 25 cmH2O + ECCO2R	Device: PrismaLung; Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator
ACTIVE_COMPARATOR: Standard; Tidal volume 6 ml/kg PBW and PEEP based on the ARDSNet PEEP/FiO2 table (ARMA) without ECCO2R	Device: PrismaLung; Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PaCO2	20 % decrease in PaCO2 after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW versus 4 ml/kg PBW without ECCO2R.	15 min after initiation of ECCO2R (PrismaLung) at tidal volume of 4 ml/kg PBW (during the first part of the study).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PaCO2	Arterial blood gas	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.
CO2 removal rate	Using both the blood side and the gas side equation	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.
Respiratory mechanics work of breathing	Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)	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.
Transpulmonary pressure	Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)	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.
Work of breathing	Using oesophageal ballon (NutriVent catheter) and FluxMed monitor (MBMed)	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.
EIT	Electrical Impedance Tomography using BB² (Swisstom)	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.
EELV	End expiratory Lung volume using nitrogen wash-in wash-out method (Engstrom GE)	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.
Plasma Cytokines	Elisa using plasma samples	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Pulmonary Cytokines	Elisa using BAL samples	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Pulmonary Type III Procollagen	RIA using plasma and BAL samples	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Pulmonary Inflammatory and Fibrotic pathway	mRNA	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.

Other Outcome Measures

Outcome Measure	Time Frame
Plasma Free Hemoglobin	q24 h, up to 72 h
Haptoglobin	q24 h, up to 72 h
Lacticodéshydrogenase (LDH)	q24 h, up to 72 h
schizocytes	q24 h, up to 72 h
Bilirubin	q24 h, up to 72 h

Collaborators and Investigators

• Sponsor: Hôpital Européen Marseille

Publications and helpful links

General Publications

• 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. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 12, 2017
• Primary Completion (ACTUAL): October 13, 2017
• Study Completion (ACTUAL): December 20, 2017

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (ESTIMATE): December 29, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2018
• Last Update Submitted That Met QC Criteria: March 10, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 2016-A01523-48

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No