Clinical trial NCT02586948: Physiological Study of Minimally Invasive ECCO2R in Exacerbations of COPD Requiring Invasive Mechanical Ventilation
Official title: Physiological Study of Minimally Invasive Extracorporeal CO2 Removal in Exacerbations of COPD Requiring Invasive Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: extracorporeal CO2 removal
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Alung Technologies
First posted: 2015-10-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: intrinsic PEEP (PEEPi)
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
Secondary outcomes:
measure: Functional Residual capacity (FRC)
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
measure: PaO2
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
measure: PaCO2
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
measure: Arterial O2 saturation
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
measure: pH
timeFrame: 12 hours (between measurements at baseline and under ECCO2R)
measure: amount of sedative drugs
timeFrame: Average time period of 6 days
measure: length of intubation
timeFrame: Average time period of 7 days, up to 28 days
measure: length of ICU-stay
timeFrame: Average time period of 8 days, up to 28 days
measure: length of hospital stay
timeFrame: Average time period of 9 days, up to 28 days
measure: ICU mortality
timeFrame: Average time period of 9 days, up to 28 days
measure: catheter related complications
timeFrame: Average time period of 9 days
measure: Hemolung related complications
timeFrame: Average time period of 9 days
measure: non catheter-related bleedings
timeFrame: Average time period of 9 days
measure: work of breathing per Liter
timeFrame: Average time period of 7 days
measure: work of breathing per minute
timeFrame: Average time period of 7 days
measure: work of breathing per breath
timeFrame: Average time period of 7 days
measure: Occlusion pressure in 100msec (P0.1)
timeFrame: Average time period of 7 days
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Kremlin Bicetre
country: France
facility: Hopital de Bicetre, Hopitaux universitaires Paris Sud
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Luc Diehl
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.