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

Chronic Obstructive Pulmonary Disease Clinical Trial

— EPHEBE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02586948
• Other study ID #: HAO14044
• Status: Completed
• Phase: N/A
• First received: August 31, 2015
• Last updated: February 26, 2018
• Start date: July 2016
• Est. completion date: February 12, 2018

Study information

• Verified date: February 2018
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 12, 2018
• Est. primary completion date: January 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Device:
• extracorporeal CO2 removal (Hemolung device)
ECCO2R in severe exacerbation of COPD patients, requiring invasive mechanical ventilation with persistent respiratory acidosis and dynamic hyperinflation

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	Hopital de Bicetre, Hopitaux universitaires Paris Sud	Kremlin Bicetre
France	Hopital Europeen Georges Pompidou	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Alung Technologies

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Functional Residual capacity (FRC)	FRC using the nitrogen washout method, expressed in mL	12 hours (between measurements at baseline and under ECCO2R)
Secondary	PaO2	PaO2 expressed in mmHg	12 hours (between measurements at baseline and under ECCO2R)
Secondary	PaCO2	PaCO2 expressed in mmHg	12 hours (between measurements at baseline and under ECCO2R)
Secondary	Arterial O2 saturation	Arterial O2 saturation expressed in %	12 hours (between measurements at baseline and under ECCO2R)
Secondary	pH	pH expressed in absolute value	12 hours (between measurements at baseline and under ECCO2R)
Secondary	amount of sedative drugs	amount of sedative drugs (per day and cumulative)	Average time period of 6 days
Secondary	length of intubation	length of intubation (days)	Average time period of 7 days, up to 28 days
Secondary	length of ICU-stay	length of ICU-stay (days)	Average time period of 8 days, up to 28 days
Secondary	length of hospital stay	length of hospital stay (days)	Average time period of 9 days, up to 28 days
Secondary	ICU mortality	Number of in ICU-deceased participants (expressed in absolute number and %)	Average time period of 9 days, up to 28 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	work of breathing per minute	work of breathing with and without ECCO2R, expressed in Joules per minute	Average time period of 7 days
Secondary	work of breathing per breath	work of breathing with and without ECCO2R, expressed in Joules per breath	Average time period of 7 days
Secondary	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