Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung

Acute Respiratory Distress Syndrome Clinical Trial

— PROVAP  

Official title:

Enhanced Lung Protective Ventilation for ARDS Patients With PrismaLung

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03004885
• Other study ID #: 2016-A01523-48
• Status: Terminated
• Phase: N/A
• First received: December 14, 2016
• Last updated: March 10, 2018
• Start date: October 12, 2017
• Est. completion date: December 20, 2017

Study information

• Verified date: March 2018
• Source: Hôpital Européen Marseille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 20, 2017
• Est. primary completion date: October 13, 2017
• 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 = 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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Device:
• PrismaLung
Low flow Extracorporeal CO2 removal using a 0.32 m² membrane oxygenator

Locations

Country	Name	City	State
France	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		q24 h, up to 72 h
Other	Haptoglobin		q24 h, up to 72 h
Other	Lacticodéshydrogenase (LDH)		q24 h, up to 72 h
Other	schizocytes		q24 h, up to 72 h
Other	Bilirubin		q24 h, up to 72 h
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Plasma Cytokines	Elisa using plasma samples	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Secondary	Pulmonary Cytokines	Elisa using BAL samples	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.
Secondary	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.
Secondary	Pulmonary Inflammatory and Fibrotic pathway	mRNA	Only in the third part, measurement at baseline, 1 hour and 22 hours in each arm.