Correction by ECCO2-R of Hypercapnia in Patients With DVP in Moderate to Severe ARDS Under Protective Ventilation. (COVAP)

Study of Carbon Dioxide Removal to Alleviate Right Ventricule Dysfunction During Acute Respiratory Distress Syndrome

Pulmonary vascular dysfunction (DVP) is associated with a pejorative prognosis during ARDS. There is no specific therapeutic intervention to thwart it. Extracorporeal CO2 purification (ECCO2-R) is a technique that has been very rapidly diffused and adopted in intensive care since commercialization of the devices but, the formal clinical evaluation is insufficient. It could significantly improve the prognosis of patients with both DVP and refractory hypercapnia.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; Hypercapnia
• Intervention / Treatment: Device: Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)

Detailed Description

This is a prospective, non-comparative, open-label, multicenter regional study, without random drawing or blindfolding.

The primary objective of the study is the correction by ECCO2-R of hypercapnia in patients with DVP in moderate to severe ARDS under protective ventilation.

The primary endpoint is the percentage of patients with hypercapnia correction (defined as a 20% decrease in PaCO2 at H2 of ECCO2-R initiation).

The secondary objectives are:

• Demonstrate that ECCO2-R allows in hypercapnic ARDS and DVP patients to correct hypercapnia with H6 and H24, improve DVP and hemodynamics, reduce alveolar dead space, improvement of respiratory mechanics
• Assess the tolerance of the evaluated technique.

The Secondary endpoints are:

- Relative change of capnia to H6 and H24 in relation to H0; proportion of patients with a decrease of at least 20% of PaCO2 to H6 and H24; changes in echocardiographic indices; hemodynamic parameters; alveolar deadspace and respiratory mechanics to H2, H6 and H24, compared to H0; Complications, Mortality at reanimation discharge (or on D28 if this date occurs before discharge of reanimation).

The intervention is based on the use of ECCO2-R (PrismaLung®, Prismaflex ® Baxter) in eligible patients. ECCO2-R will be initiated as soon as possible after inclusion, for a duration of at least 24 H (possibly prolonged up to 72 H at the decision of reanimator), by jugular or femoral vein-venous.

The size of the catheters, the machine settings, in particular the blood flow and sweep will be standardized according to the state of the art and the recommendations of the manufacturer

The ECO2R venous technique uses devices consisting of a monitor, an exchanger and a pump.

1. The PrismaLung® Kit (Baxter): Single-use EC-marked extracorporeal circuit intended for use for at least 24 hours (maximum 72 hours).

   The PrismaLung® kit is intended for use with the Prismaflex® monitor with software version 8.10 or later and its support in conjunction with Prismaflex® single use treatment sets.

2. The Prismaflex HP-X Set (Baxter): blood line set for extracorporeal blood circulation, EC marked or the HF 1400® set (Baxter) (for extra-corporeal CO2 purification combined with purification).
3. The Prismaflex® monitor (Baxter), EC marked, is used routinely in intensive care (continuous extra-renal purification, therapeutic plasma exchange, haemoperfusion, hemopurification).

So that each center has a dedicated monitor for research, this device will be provided by the Baxter laboratory. The monitor will be equipped with a holder for the Prismalung kit marked CE.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94000
    • Henri Mondor Hospital

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:

• Moderate to severe ARDS according to the Berlin definition;
• Pulmonary vascular dysfunction at echocardiography (pulmonary arterial hypertension, right ventricular dilatation or dyskinesia of the interventricular septum);
• Refractory hypercapnia, defined by a PaCO2 ≥48 mmHg in spite of the reduction of the instrumental dead space and the increase of the respiratory rate.
• Free and informed written consent for persons in a position to consent; consent of the support person/parent/relative in case of incapacity to consent; inclusion in emergency situations (Article L1122-1-2 of the CSP)

Exclusion Criteria:

• Age <18 years;
• Known pregnancy or breastfeeding;
• Contra-indication to curative anticoagulation, thrombocytopenia <50 G / L, heparin-induced thrombocytopenia, known hypersensitivity to heparin or to compounds;
• Femoral or jugular venous access impossible;
• Refractory hypoxemia with indication at ECMO;
• No affiliation to social security or beneficiary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Extracorporeal CO2 removal; Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter)

Device: Extracorporeal CO2 removal (ECCO2-R) (PrismaLung®, Prismaflex ® Baxter); A low-flow CO2 removal device (Prismalung®, Baxter) will be used with a conventional renal replacement therapy (RRT) platform (Prismaflex®, Baxter). In patients already treated with continuous RRT because of renal failure or metabolic acidosis, the HF 1400® (Baxter) set will be used to combine RRT and decarboxylation. Gas flow through the gas exchanger will be set up to 10 L/min, with an oxygen concentration from 0.21 to 1 and a blood flow of 200-400 mL/min. Patients will be ventilated with a target tidal volume of 6 ml/kg (predicted body weight) and a target plateau pressure below 30 cmH2O.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with corrected hypercapnia	20% decrease in PaCO2 two hours after ECCO2-R initiation	at hour 2 (H2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change of capnia at H6 and H24 after ECCO2-R		at hour 6 (H6), at hour 24 (H24)
Proportion of patients with a decrease of at least 20% of PaCO2 to H6 and H24		H6, H24
Changes in echocardiographic indices	Changes in echocardiographic indices at H2, H6 and H24	H2, H6, H24
Changes in hemodynamic parameters	Changes in hemodynamic parameters at H2, H6 and H24	H2, H6, H24
Changes in alveolar deadspace	Changes in alveolar deadspace at H2, H6 and H24	H2, H6, H24
Changes in respiratory mechanics	Changes in respiratory mechanics at H2, H6 and H24	H2, H6, H24
Number of complications related to ECCO2-R technique		ICU Discharge or day 28
Percentage of mortality		ICU discharge or day 28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Armand Mekontso Dessap, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): February 25, 2019
• Study Completion (Actual): March 21, 2019

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: ARDS; Extracorporeal CO2 removal (ECCO2-R)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Hypercapnia
• Other Study ID Numbers: P160701; 2016-A01689-42 (Other Identifier: IDRCB)

Drug and device information, study documents

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