Clinical Trials Register

Summary
EudraCT Number:	2008-006173-33
Sponsor's Protocol Code Number:	ALMED-07-C3-009
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-09-07
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2008-006173-33

A.3

Full title of the trial

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. The E.C.H.O.ICU trial.

Etude internationale de Phase III, randomisée, comparant dans les
exacerbations sévères de Broncho-Pneumopathie Chronique Obstructive l’efficacité de l’Hélium/Oxygène avec celle de l’Air/Oxygène administrés en ventilation spontanée et en ventilation non invasive intermittente. Etude E.C.H.O.ICU

A.3.2

Name or abbreviated title of the trial where available

E.C.H.O. ICU Trial

A.4.1

Sponsor's protocol code number

ALMED-07-C3-009

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Air Liquide Santé International
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Air Liquide Santé International
B.5.2	Functional name of contact point	Dr Joelle TEXEREAU
B.5.3	Address:
B.5.3.1	Street Address	CRCD - 1 chemin de la Porte des Loges - B.P 126
B.5.3.2	Town/ city	Les Loges en Josas
B.5.3.3	Post code	78354
B.5.3.4	Country	France
B.5.4	Telephone number	33139 07 65 18
B.5.5	Fax number	33139 07 61 99
B.5.6	E-mail	joelle.texereau@airliquide.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Oxygène Médical Air Liquide Santé France
D.2.1.1.2	Name of the Marketing Authorisation holder	Air Liquide Santé International
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Medical Oxygen
D.3.4	Pharmaceutical form	Inhalation gas
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxygen
D.3.9.1	CAS number	7782-44-7
D.3.9.3	Other descriptive name	Medical Oxygen, BOC, LINDE, CARBAGAS, ALM BELGIQUE, ALSF, AL Gmbh, RIVOLTRA
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	range
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Helium/Oxygen 78%/22%
D.3.2	Product code	Helium Oxygen
D.3.4	Pharmaceutical form	Inhalation gas
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Oxygen
D.3.9.1	CAS number	7782-44-7
D.3.9.3	Other descriptive name	OXYGEN
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	20 to 24
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Helium
D.3.9.1	CAS number	7440-59-7
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	76 to 80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients eligible for this study are critically ill patients with COPD admitted in ICU for an exacerbation of their chronic disease with hypercapnic acute respiratory failure.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10009033
E.1.2	Term	Chronic obstructive pulmonary disease
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of Helium/Oxygen 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

E.2.2

Secondary objectives of the trial

- To assess short term and long term efficacy criteria
- To assess the safety of the administration of the He/O2 78%/22% in ICU
- To evaluate medico-economic data

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Male or female patient, aged ≥ 35 years,
2)Patient with known or suspected COPD,
3)Patient presenting current exacerbation of COPD with hypercapnic acute respiratory failure,
4)Patient presenting the following criteria for starting Non-Invasive
Ventilation (NIV) sessions:
4.a) PaCO2 ≥ 45 mmHg (6.0 kPa), AND arterial pH ≤ 7.35,
And at least 1 of the following:
4.b) Respiration rate ≥ 25 breaths per minute,
or
4.c) PaO2 ≤ 50 mmHg (6.7 kPa) or SaO2 ≤ 90% or SpO2 ≤ 90%,
5)Patient admitted in an ICU,
6)Written informed consent signed and dated by the patient or next of kin after full explanation of the study by the investigator prior to participation,

E.4

Principal exclusion criteria

7) Patient previously randomised in the study,
8) Patient admitted in the ICU for more than 24 hours and/or having received Non-Invasive Ventilation (NIV) in ICU for more than 6 hours (in total) for the current exacerbation of COPD,
9) Patient with tracheostomy,
10) Patient who had lung transplant,
11) Patient having a contraindication to NIV:
11.a) Respiratory arrest, severe acute respiratory failure with high probability of imminent intubation,
11.b) Sustained haemodynamic instability (hypotension with systolic blood pressure < 90 mmHg despite volume loading and/or administration of vasopressor treatment),
11.c) Coma, impaired consciousness, uncooperative patient, neurologic instability not due to acute hypercapnia (e.g., stroke, substance abuse or withdrawal, …),
11.d) Shock or multiple organ failure syndrome,
11.e) Severe ventricular rhythm disorders,
11.f) Uncontrollable vomiting,
11.g) Recent facial or gastro-oesophageal surgery, severe craniofacial trauma,
12) Patient requiring oxygen flow rate > 6 L/min or FIO2 > 0.50,
13) Patient with acute respiratory failure believed to be attributable to a current significant chronic disease other than COPD (asthma, significant bronchiectasis, cystic fibrosis, sarcoidosis, lung fibrosis, kyphoskoliosis, neuromuscular disease, …), or to severe pulmonary embolism, extensive pneumonia or pneumothorax (either currently documented and not drained at selection or recent episode < 1 month),
14) Patient with severe concomitant chronic systemic disease with a limited probability of survival (< 6 months),
15) Pregnant or lactating woman,
16) Patient with known or suspected allergy to facemask compounds,
17) Patient who has received another investigational drug within 30 days prior to selection.

E.5 End points

E.5.1

Primary end point(s)

NIV failure (i.e., endotracheal intubation and/or death) during the index ICU stay for each randomised patient

E.5.2

Secondary end point(s)

Duration of index ICU stay and duration of index hospitalisation
Time interval between the discharge of the index ICU stay and the first re-admission in ICU for severe exacerbation of COPD
Duration of NIV sessions during the index ICU stay
Duration of invasive ventilation
Physiological and laboratory parameters
Adverse events
Medico-economic parameters

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Switzerland

Tunisia

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Emergency because severe hypercapnic exacerbations of Chronic Obstructive Pulmonary Disease (COPD).

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

370

F.4.2.2

In the whole clinical trial

670

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-10-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-09-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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