Clinical Trials Register

Summary
EudraCT Number:	2015-004959-50
Sponsor's Protocol Code Number:	Heliox-AP
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-03
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2015-004959-50

A.3

Full title of the trial

HELIOX-DRIVEN BETA2-AGONISTS NEBULIZATION FOR CHILDREN WITH MODERATE TO SEVERE ACUTE ASTHMA: A RANDOMIZED CONTROLLED TRIAL

HELIOX COMO VEHÍCULO EN LA NEBULIZACIÓN DE BETA 2-AGONISTAS EN NIÑOS CON ASMA AGUDO MODERADO-SEVERO: ENSAYO CLÍNICO CONTROLADO ALEATORIZADO

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

HELIOX-DRIVEN BETA2-AGONISTS NEBULIZATION FOR CHILDREN WITH MODERATE TO SEVERE ACUTE ASTHMA: A RANDOMIZED CONTROLLED TRIAL

HELIOX COMO VEHÍCULO EN LA NEBULIZACIÓN DE BETA 2-AGONISTAS EN NIÑOS CON ASMA AGUDO MODERADO-SEVERO: ENSAYO CLÍNICO CONTROLADO ALEATORIZADO

A.3.2

Name or abbreviated title of the trial where available

Heliox-AP

A.4.1

Sponsor's protocol code number

Heliox-AP

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	S.E. Carburos Metálicos S.A. grupo Air Products
B.1.3.4	Country	Spain
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	S.E. Carburos Metálicos S.A. grupo Air Products
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	S.E. Carburos Metálicos S.A. grupo Air Products
B.5.2	Functional name of contact point	European Regulatory Affairs Manager
B.5.3	Address:
B.5.3.1	Street Address	C/ Quintanavides 17, edificio 3
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28050
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034916579472NA
B.5.5	Fax number	0034916579536NA
B.5.6	E-mail	hoischv@airproducts.com

D. IMP Identification
D.IMP: 1
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	Heliox (Helium 22% Oxygen 78%)
D.3.4	Pharmaceutical form	Medicinal gas, compressed
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.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	22
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	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	Aire Medicinal Sintético Carburos Metálicos, 22% v/v gas medicinal, comprimido
D.2.1.1.2	Name of the Marketing Authorisation holder	S.E. Carburos Metálicos, S.A.
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Aire Sintético Medicinal
D.3.4	Pharmaceutical form	Medicinal gas, compressed
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	Oxigeno Medicinal Gas Carburos Metálicos
D.3.9.4	EV Substance Code	SUB14733MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	22
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

Moderate to severe exacerbations of asthma

EXACERVACION DE ASMA AGUDO DE MODERADO A GRAVE

E.1.1.1

Medical condition in easily understood language

Moderate to severe exacerbations of asthma

EXACERVACION DE ASMA AGUDO DE MODERADO A GRAVE

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10064823
E.1.2	Term	Asthmatic crisis
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

The main objective of this study is to evaluate the efficacy of the use of heliox (He/O2 = 78%/22%) as a discontinuous nebulizer of rapid-acting beta2-agonists (salbutamol) compared to Air Synthetic Medicinal (O2 22%/N2 78%), in children and adolescents with acute severe asthma, attending to an Emergency Department.
The authors hypothesized that nebulization using heliox (because it reduces the turbulent flow and increases the deposition of aerosolized particles)could show greater clinical improvement than Air Synthetic nebulization, in children and adolescents with acute severe asthma, treated with salbutamol.
The secondary objective of the study is to evaluate the safety of the treatment, especially in the hypoxia events (SaO2 < 90%) suffered by the patients. Patients with very severe crisis can present a desaturation, requiring higher O2 levels than air or heliox mix used.

El objetivo 1º consiste en la evaluación de la eficacia del uso de heliox(He/O2=78%/22%)para nebulizar en forma intermitente broncodilatadores agonistas beta de acción rápida (salbutamol)en comparación con el uso de aire sintético medicinal(O2 22%/N2 78%)en niños y adolescentes con asma aguda grave que consultan en un S.U.La hipótesis planteada en el estudio es que, en el caso de niños y adolescentes con asma aguda grave tratados con salbutamol, la nebulización con heliox(al reducir el flujo turbulento e incrementar el depósito de partículas aerosolizadas)puede traducirse en mejorías clínicas en comparación con la nebulización con aire sintético medicinal.Un 2º objetivo consiste en la evaluación de la seguridad del tratamiento,en especial de los episodios de hipoxia que puedan experimentar los pacientes.Algunos pacientes con crisis muy severas pueden presentar desaturación requiriendo niveles de O2 mayores a los que presenta el aire sintético medicinal o la mezcla de heliox utilizada.

E.2.2

Secondary objectives of the trial

*Percentage of patients that suffered early termination of the study due to SaO2 < 90%.
*Percentage of patients that suffered early termination of the study due to PS = 0.
*Percentage of patients in which hospitalization is required at the end of the treatment.
*Percentage of patients that require ITU hospitalization, orotracheal intubation or exitus during the study.
*Pulmonary function [Change of PEF with respect to basal value, measured by flow meter in patients who can perform forced expiratory manoeuvre (the best of three measures)].*
*Number of hypoxia episodes [SaO2 < 90%] occurred during the treatment and that could require an increase in O2 administration or patient withdrawal.

Como variables secundarias serán consideradas:
• Porcentaje de pacientes con finalización anticipada del ensayo por (SaO2< 90%).
• Porcentaje de pacientes con finalización anticipada del ensayo por (EP = 0).
• Porcentaje de pacientes que requieran hospitalización al final del tratamiento.
• Porcentaje de pacientes que requieran ingreso a UTI, intubación oro-traqueal o que fallezcan durante el protocolo.
• Función pulmonar (cambio del FEM desde el valor basal, medido mediante un flujímetro en aquellos pacientes que puedan realizar la maniobra espiratoria forzada [se tomará la mejor de tres medidas]).*
• Número de episodios de hipoxia [SaO2 < 90%] que ocurran durante el tratamiento y que pueden requerir aumento del nivel de O2 administrado o la salida del paciente del protocolo).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All inclusion criteria are:
(1)All participants or their parents or guardians will give their informed written consent to participate.
(2) Age 6-16 years.
(3) Diagnosis of asthma according to the guidelines.
(4) Patients attending to an ED for an acute exacerbation.
(5) Pulmonary score of ≥ 4

Los criterios de inclusión para los participantes son:
(1) Todos los participantes o sus padres o tutores proporcionarán su consentimiento por escrito para participar.
(2) Edad entre 6 - 16 años.
(3) Diagnóstico de asma, de acuerdo con las directrices reconocidas internacionalmente.
(4) Pacientes que acudan a un servicio de urgencia (S.U.) por una exacerbación aguda.
(5) Puntuación del EP ≥ 4 (Tabla 1 [31]).

E.4

Principal exclusion criteria

(1) Altered consciousness.
(2) Pulse oximetry reading of less than 90%
(3) Systolic blood pressure greater than 180 mm Hg,
(4) Patients requiring non-invasive ventilation, or intubation and/or mechanical ventilation.
(5) Other concomitant diseases than asthma.
(6) Be treated with corticosteroids until 6 hours before

(1) Alteración de la consciencia.
(2) Una saturometría de pulso menor del 90 % al aire.
(3) Una presión arterial sistólica superior a 180 mm Hg.
(4) Requerir ventilación no invasiva, o intubación y/o ventilación mecánica.
(5) Presentar otras enfermedades concomitantes, aparte del asma.
(6) Haber recibido corticosteroides en las 6 horas previas.

E.5 End points

E.5.1

Primary end point(s)

The main objective of this study is to evaluate the efficacy of the use of heliox (He/O2 = 78%/22%) as a discontinuous nebulizer of rapid-acting beta2-agonists (salbutamol) compared to Air Synthetic Medicinal (O2 22%/N2 78%), in children and adolescents with acute severe asthma, attending to an Emergency Department.
The authors hypothesized that nebulization using heliox (because it reduces the turbulent flow and increases the deposition of aerosolized particles) could show greater clinical improvement than Air Synthetic nebulization, in children and adolescents with acute severe asthma, treated with salbutamol.
The secondary objective of the study is to evaluate the safety of the treatment, especially in the hypoxia events (SaO2 < 90%) suffered by the patients. Patients with very severe crisis can present a desaturation, requiring higher O2 levels than air or heliox mix used.

El objetivo principal de este estudio consiste en la evaluación de la eficacia del uso de heliox (He/O2 = 78%/22%) para nebulizar en forma intermitente broncodilatadores agonistas beta de acción rápida (salbutamol) en comparación con el uso de aire sintético medicinal (O2 22%/N2 78%) en niños y adolescentes con asma aguda grave que consultan en un servicio de urgencia. La hipótesis planteada en este estudio es que, en el caso de niños y adolescentes con asma aguda grave tratados con salbutamol, la nebulización con heliox (al reducir el flujo turbulento e incrementar el depósito de partículas aerosolizadas) puede traducirse en mejorías clínicas en comparación con la nebulización con aire sintético medicinal. Un segundo objetivo del estudio consiste en la evaluación de la seguridad del tratamiento, en especial de los episodios de hipoxia que puedan experimentar los pacientes. Algunos pacientes con crisis muy severas pueden presentar desaturación requiriendo niveles de O2 mayores a los que presenta el aire sintético medicinal o la mezcla de heliox utilizada.

E.5.1.1

Timepoint(s) of evaluation of this end point

30, 60, and 90 min.

30, 60, Y 90 min.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

30, 60, and 90 min.

30, 60, Y 90 min.

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

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

30 June 2016

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-12-03.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric population

Población pediatrica

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

F.4.2.2

In the whole clinical trial

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)

Routine clinical practice

Practica clínica habitual

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-18

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials