Clinical Trials Register

Summary
EudraCT Number:	2021-001429-34
Sponsor's Protocol Code Number:	TRITEX_COPD
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-10-06
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

Spain - AEMPS

A.2

EudraCT number

2021-001429-34

A.3

Full title of the trial

Utility of inhaled extrafine triple therapy with glycopyrronium bromide, formoterol fumarate dihydrate and beclometasone dipropionate to improve expiratory flow limitation in severe COPD exacerbations. An double-blind randomized controlled trial.

A.3.1

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

Utility of inhaled triple therapy to improve expiratory flow limitation in severe COPD exacerbations.

A.3.2

Name or abbreviated title of the trial where available

TRITEX_COPD

A.4.1

Sponsor's protocol code number

TRITEX_COPD

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	University Hospital Mutua de Terrassa
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Mutua Terrassa
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	University Hospital Mutua of Terrassa
B.5.2	Functional name of contact point	Complex chronic patient care unit
B.5.3	Address:
B.5.3.1	Street Address	Pza. Dr Robert, 5,
B.5.3.2	Town/ city	Terrassa
B.5.3.3	Post code	08226
B.5.3.4	Country	Spain
B.5.6	E-mail	palmagro@mutuaterrassa.es

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	TRIMBOW 87 micrograms/5 micrograms/9 micrograms
D.2.1.1.2	Name of the Marketing Authorisation holder	CHIESI FARMACEUTICI, S.P.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.3.4	Pharmaceutical form	Inhalation solution
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	FORMOTEROL
D.3.9.1	CAS number	73573-87-2
D.3.9.4	EV Substance Code	SUB07788MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534-09-8
D.3.9.4	EV Substance Code	SUB00681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	348
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Glycopyrronium bromide
D.3.9.1	CAS number	596-51-0
D.3.9.4	EV Substance Code	SUB07951MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	36
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation vapour, solution
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe exacerbation of chronic obstructive pulmonary disease (COPD)

E.1.1.1

Medical condition in easily understood language

Exacerbations of a lung disease called chronic obstructive pulmonary disease (COPD)

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10010953
E.1.2	Term	COPD exacerbation
E.1.2	System Organ Class	100000004855

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 compare the usual treatment for severe exacerbations vs inhaled extrafine triple therapy with formoterol, glycopyrronium, and beclomethasone in a single device (TRIMBOW) in addition to the usual treatment, during the first three days of hospitalization in patients previously treated with LABA + LAMA, LABA + ICs, or LABA + LAMA + ICs.
The primary endpoint is changes in expiratory flow limitation evaluated with the difference between inspiratory and expiratory reactance measured by impulse oscillometry, between the first and the third day of hospitalization, before the first daily administration of SABA and SAMA (with or without triple therapy according to randomization)

E.2.2

Secondary objectives of the trial

1. Changes in expiratory flow limitation, between the first and the third day of hospitalization, 30 minutes after the first daily administration of SABA and SAMA (with or without triple therapy according to randomization).
2. Changes in dyspnea measured with the validated Spanish version of the Dyspnea-12 questionnaire and a 10 cm. visual analogue dyspnea scale, before the first daily administration of bronchodilators, between the first and the third day of hospitalization.
3. Length of hospital stay.
4. Required rescue doses of SABA and SAMA.
5. Readmissions 1 month after hospital discharge.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients 40 years and older.
2. Accepting participation in the study and signing informed consent.
3. Previous diagnosis of COPD confirmed by spirometry.
4. Currently requiring hospitalization for COPD exacerbation.
5. Domiciliary treatment in stable phase with triple therapy (LABA + LAMA + ICs), combined bronchodilation (LABA + LAMA) or (LABA + ICs) at least two months before current exacerbation.

E.4

Principal exclusion criteria

1. Myocardial infarction or unstable angina event in the last month or at time of admission.
2. Uncontrolled arrhythmias (flutter, atrial fibrillation, or ventricular arrhythmias) that, in the opinion of the investigators, contraindicate administration of β-mimetics or anticholinergics.
3. COPD exacerbation requiring invasive or non-invasive mechanical ventilation or intensive care unit admission on the first day of hospitalization.
5. Inability to perform the inhaled treatment (SABA and SAMA with or without TRIMBOW) correctly with the Aerochamber Plus Flow chamber with a facial mask (cognitive impairment, delirium, altered level of consciousness).
6. Inability to perform respiratory function tests with the impulse oscillometer device (Resmon ProFull) or inability to complete dyspnea questionnaires.
7. Pregnancy or being of fertile age.
8. Severe renal impairment (CKD-EPI <15 mL/min/1.73m2) or dialysis.
9. Pneumonia, acute pulmonary edema, pneumothorax as the main causes of hospital admission.
10. Bronchiectasis or asthma as a predominant disease.
11. Hospitalization for severe exacerbation of COPD in the previous month.
12. History of lung reduction or lung transplant surgery.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is a change in expiratory flow limitation, before first morning treatment with bronchodilators, and a minimal washout period of 12 hours without long-acting bronchodilators, between the first and third days after randomisation. Expiratory flow limitation will be measured with an impulse oscillometer device (Resmon Pro Full) and calculated as the difference between inspiratory reactance (Xrsinsp) and expiratory reactance (Xrsexp) (∆Xrs =Xrsinsp - Xrsexp).

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year

E.5.2

Secondary end point(s)

1. Changes in expiratory flow limitation between the first and third days of hospitalizations measured 30 minutes after the first daily administration of bronchodilators.
2. Changes in dyspnea questionnaires completed by patient before first morning bronchodilator treatment between the first and third days after randomisation.
3. Days of hospitalization number of short-acting bronchodilator rescue doses.
4. Readmissions 1 month after hospital discharge.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year

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

E.6.5

Efficacy

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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

LVLS

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

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.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

None

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

2021-10-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-28

P. End of Trial
P.	End of Trial Status	Ongoing

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