Physiological Study of Minimally Invasive ECCO2R in Exacerbations of COPD Requiring Invasive Mechanical Ventilation (EPHEBE)

Physiological Study of Minimally Invasive Extracorporeal CO2 Removal in Exacerbations of COPD Requiring Invasive Mechanical Ventilation

Morbidity and mortality in COPD result largely of acute exacerbations.The optimization of the respiratory management represents a fundamental challenge for improving prognosis and reducing mortality. While the hospital mortality of patients treated with NIV has decreased over years, and is currently less than 10 %, mortality in patients treated with invasive ventilation remains higher than 25%. To improve the prognosis of patients with acute exacerbation of COPD requiring invasive mechanical ventilation is therefore a major challenge in terms of morbidity and mortality. Among the means available to achieve this goal, minimally invasive extracorporeal CO2 removal (ECCO2R) seems to be a very promising approach.

The investigators hypothesize that the addition of minimally invasive ECCO2R is likely to limit dynamic hyperinflation in COPD patients requiring invasive mechanical ventilation for an acute exacerbation, while improving gas exchange.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: extracorporeal CO2 removal (Hemolung device)

Detailed Description

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death in the U.S. and is expected to become the third leading cause of death in 2020. Morbidity and mortality in COPD result largely of acute exacerbations, which are responsible for 1.5 million ED visits and 750,000 hospitalizations per year in the U.S. The optimization of the respiratory management of acute exacerbations represents a fundamental challenge for improving prognosis and reducing mortality. The value of non-invasive ventilation (NIV) for severe acute exacerbations of COPD was formally demonstrated by randomized clinical trials. In the setting of severe COPD exacerbations, NIV is actually very largely employed, largely ahead from invasive mechanical ventilation. While the hospital mortality of patients treated with NIV has decreased over years, and is currently less than 10 %, mortality in patients treated with invasive ventilation remains as high than 25%. Mortality in patients treated with invasive ventilation after failure of NIV seems to be growing and is actually close to 30%. To improve the prognosis of patients with acute exacerbation of COPD requiring invasive mechanical ventilation is therefore a major challenge in terms of morbidity and mortality. Among the means available to achieve this goal, minimally invasive extracorporeal CO2 removal (ECCO2R) seems to be a very promising approach.

The investigators hypothesize that the addition of minimally invasive ECCO2R is likely to limit dynamic hyperinflation in COPD patients requiring invasive ventilation for an acute exacerbation, while improving gas exchange. If confirmed, it could imply a more rapid weaning from invasive ventilation in relation to:

• less hemodynamic consequences of positive pressure ventilation
• reduced risk of baro-volo trauma of the lung parenchyma
• reduction in the use of sedative drugs
• a chest configuration minimizing diaphragmatic flattening, therefore favoring the generation of higher trans-diaphragmatic pressures
• a decrease in the work of breathing (WOB), in connection with the previous point and with a decrease in alveolar ventilation required for pulmonary CO2 elimination during the ECCO2R treatment All of these elements are clinically relevant, as a reduction in the duration of invasive ventilation is associated in the literature with a decrease in the incidence of pneumonia associated with mechanical ventilation, as well as with a decrease in the duration of ICU-stay.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49933
    • CHU d'Angers
  • Kremlin Bicetre, France, 94275
    • Hopital de Bicetre, Hopitaux universitaires Paris Sud
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou

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:

• clinical exacerbation of a known or suspected COPD
• intubation and invasive mechanical ventilation since less than 72 hrs.
• ACV or CV mode (VT 8 ml/kg, RR 12/min., PEEP : 0 cmH20)
• pH < 7.30 and PaCO2 > 55 mm Hg and PEEPi (end-expiratory occlusion) > 5 cmH20
• written inform consent (patient, patient's legal surrogate)
• affiliation to a social security regime

Exclusion Criteria:

• Body Mass Index (BMI) > 35 kg/m2
• PaO2/FiO2 < 200 mm Hg
• history of hemorrhagic stroke
• heparin-induced thrombocytopenia
• Severe thrombopenia type II history

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: extracorporeal CO2 removal; extracorporeal CO2 removal initiated shortly after intubation, using the veno-venous Hemolung device	Device: extracorporeal CO2 removal (Hemolung device); ECCO2R in severe exacerbation of COPD patients, requiring invasive mechanical ventilation with persistent respiratory acidosis and dynamic hyperinflation; Other Names: ECCO2R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intrinsic PEEP (PEEPi)	PEEPi at baseline and after ECCO2R by the Hemolung® device and adjustment of ventilator settings, expressed in cmH20	12 hours (between measurements at baseline and under ECCO2R)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Residual capacity (FRC)	FRC using the nitrogen washout method, expressed in mL	12 hours (between measurements at baseline and under ECCO2R)
PaO2	PaO2 expressed in mmHg	12 hours (between measurements at baseline and under ECCO2R)
PaCO2	PaCO2 expressed in mmHg	12 hours (between measurements at baseline and under ECCO2R)
Arterial O2 saturation	Arterial O2 saturation expressed in %	12 hours (between measurements at baseline and under ECCO2R)
pH	pH expressed in absolute value	12 hours (between measurements at baseline and under ECCO2R)
amount of sedative drugs	amount of sedative drugs (per day and cumulative)	Average time period of 6 days
length of intubation	length of intubation (days)	Average time period of 7 days, up to 28 days
length of ICU-stay	length of ICU-stay (days)	Average time period of 8 days, up to 28 days
length of hospital stay	length of hospital stay (days)	Average time period of 9 days, up to 28 days
ICU mortality	Number of in ICU-deceased participants (expressed in absolute number and %)	Average time period of 9 days, up to 28 days
catheter related complications	catheter related complications (thrombosis, bleeding, pneumothorax, infection) expressed in total number of complications, in average number of complications per participant and in number of patients with complications	Average time period of 9 days
Hemolung related complications	Hemolung related complications (thrombosis, bleeding) expressed in total number of complications, in average number of complications per participant and in number of patients with complications	Average time period of 9 days
non catheter-related bleedings	non catheter-related bleedings expressed in total number of bleedings, in average number of bleedings per participant and in number of patients with bleedings	Average time period of 9 days
work of breathing per Liter	work of breathing with and without ECCO2R, expressed in Joules per Liter of ventilation	Average time period of 7 days
work of breathing per minute	work of breathing with and without ECCO2R, expressed in Joules per minute	Average time period of 7 days
work of breathing per breath	work of breathing with and without ECCO2R, expressed in Joules per breath	Average time period of 7 days
Occlusion pressure in 100msec (P0.1)	Occlusion pressure in 100msec in parallel to work breathing measurements with and without ECCO2, expressed in cmH2O	Average time period of 7 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Alung Technologies
• Investigators: Principal Investigator: Jean-Luc Diehl, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Diehl JL, Piquilloud L, Vimpere D, Aissaoui N, Guerot E, Augy JL, Pierrot M, Hourton D, Arnoux A, Richard C, Mancebo J, Mercat A. Physiological effects of adding ECCO2R to invasive mechanical ventilation for COPD exacerbations. Ann Intensive Care. 2020 Sep 29;10(1):126. doi: 10.1186/s13613-020-00743-y.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): January 14, 2018
• Study Completion (Actual): February 12, 2018

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): February 27, 2018
• Last Update Submitted That Met QC Criteria: February 26, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: extracorporeal CO2 removal
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: HAO14044