Efficacy of Helium/Oxygen Compared to Air/Oxygen in Severe Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to evaluate the efficacy of Helium/Oxygen (He/O2) 78%/22% compared to a conventional Air/O2 mixture in reducing endotracheal intubation rate and mortality in patients with severe hypercapnic exacerbations of Chronic Obstructive Pulmonary Disease (COPD) during their index Intensive/Intermediate Care Unit (ICU) stay.

Detailed Description
-----------------
Patients eligible for this study are critically ill patients with COPD admitted in Intensive Care Unit for an exacerbation of their chronic disease with hypercapnic acute respiratory failure. The patients will receive an Helium/Oxygen mixture or an Air/Oxygen mixture for a maximum of 72 hours during Non-Invasive Ventilation (NIV) and NIV-free sessions. During NIV sessions, gas mixtures will be administered using a ventilator suitable for NIV with either He/O2 or Air/O2 and a NIV facemask. Patients will be followed until hospital discharge and then contacted by phone up to the 6th month after randomization.

Official Title
-----------------
An International Phase III Randomised Trial Comparing in Severe Exacerbations of Chronic Obstructive Pulmonary Disease the Efficacy of Helium/Oxygen Versus Air/Oxygen Administered During Spontaneous Breathing and Intermittent Non-Invasive Ventilation.

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Helium/Oxygen 78%/22%
* Drug: Air/Oxygen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with known or suspected COPD Patient presenting current exacerbation of COPD with hypercapnic acute respiratory failure Patient eligible for Non-Invasive Ventilation (NIV) Patient admitted in an ICU Exclusion Criteria: Patient who had lung transplant Patient having a contraindication to NIV Patient with tracheostomy Patient requiring Oxygen flow rate > 6 L/min or Inspired Oxygen Fraction (FIO2) > 0.50 Patient admitted in the ICU for more than 24 hours and/or having received NIV in ICU for more than 6 hours (in total) for the current exacerbation of COPD

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Helium/Oxygen<br>Helium/Oxygen 78%/22% will be administered for a maximum of 72 hours. | Drug: Helium/Oxygen 78%/22%<br>* The Helium/Oxygen mixture will be administered during NIV and NIV-free sessions for a maximum of 72 hours using study dedicated devices. Patients will then receive the Air/Oxygen mixture with usual devices.<br>|
| Active Comparator: Air/Oxygen<br>Air/Oxygen will be administered for a maximum of 72 hours. | Drug: Air/Oxygen<br>* The Helium/Oxygen mixture will be administered during NIV and NIV-free sessions for a maximum of 72 hours using study dedicated devices. Patients will then receive the Air/Oxygen mixture with usual devices.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of NIV failure | Endotracheal intubation and/or death | 10 days (average) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of ICU stay and duration of index hospitalisation |  | 10 days (average) | 
| Duration of invasive ventilation |  | 10 days (average) | 
| Adverse events |  | 6 months (post-randomization) | 
| Medico-economic parameters | Overall costs and cost-effectiveness | 6 months | 
| Physiological and laboratory parameters | Systolic and diastolic blood pressures, heart rate, central body temperature, arterial oxygen saturation, haematology and serum biochemistry | 10 days (average) | 
| Duration of NIV sessions | Cumulative daily duration of NIV sessions and their number during each of the 3-day treatment period and globally | 10 days (average) | 
| Time interval between the discharge of the index ICU stay and the first re-admission in ICU for severe exacerbation of COPD |  | 6 months (post-randomization) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ICU, Exacerbation of COPD, Helium/Oxygen, Non-Invasive Ventilation, Patient with known or suspected COPD, patient Admitted in an ICU, Patient presenting current exacerbation of COPD