Clinical Trials Register

Summary
EudraCT Number:	2020-005306-25
Sponsor's Protocol Code Number:	Pioneer
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-06-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-005306-25

A.3

Full title of the trial

PIrfenidone to prevent fibrOsis in ARDS. A RaNdomizEd controllEd tRial (PIONEER) GR-2019-12371063

A.3.1

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

Use of Pirfenidone in the prevention of fibrosis in patients with acute respiratory distress syndrome (ARDS): clinical trial to prevent the onset of pulmonary fibrosis in patients with ARDS

Utilizzo di Pirfenidone nella prevenzione della fibrosi in pazienti con sindrome da distress respiratorio acuto (ARDS): trial clinico per prevenire l’insorgere di fibrosi polmonare in pazienti con ARDS

A.3.2

Name or abbreviated title of the trial where available

Pioneer

A.4.1

Sponsor's protocol code number

Pioneer

A.5.4

Other Identifiers

Name:

Number:

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	OSPEDALE SAN RAFFAELE
B.1.3.4	Country	Italy
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	grant ministeriale
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS Ospedale San Raffaele
B.5.2	Functional name of contact point	Anestesia e rianimazione Cardio-Tor
B.5.3	Address:
B.5.3.1	Street Address	via Olgettina 60
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226436151
B.5.5	Fax number	0226436152
B.5.6	E-mail	landoni.giovanni@hsr.it

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	Yes
D.2.1.1.1	Trade name	Esbriet
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Esbriet
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PIRFENIDONE
D.3.9.1	CAS number	53179-13-8
D.3.9.2	Current sponsor code	na
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	801 to 2403
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute respiratory distress syndrome (ARDS)

La sindrome da distress respiratorio acuto (ARDS)

E.1.1.1

Medical condition in easily understood language

ARDS is a severe form of acute lung injury and a leading cause of intensive care unit (ICU) admissions worldwide.

L’ARDS è una forma grave di lesione polmonare acuta e una delle principali cause di ricovero in terapia intensiva (ICU) in tutto il mondo.

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	10003083
E.1.2	Term	ARDS
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determine whether administration of Pirfenidone in patients with severe or moderate ARDS is likely to increase the number of ventilator free days a day 28 after randomization

determinare se la somministrazione di Pirfenidone in pazienti affetti da ARDS severa o moderata sia in grado di aumentare il numero dei giorni liberi da ventilazione meccanica a 28 giorni dalla randomizzazione

E.2.2

Secondary objectives of the trial

Evaluate the impact of experimental treatment on survival and improvement in patient quality of life and obtain data on cell biology features of pulmonary fibrosis

valutare l'impatto del trattamento sperimentale sulla sopravvivenza e il miglioramento della qualità della vita del paziente e ottenere dati relativi a caratteristiche di biologia cellulare della fibrosi polmonare

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Concomitant presence of:
1. ARDS (moderate and severe)
2. Inflammatory ARDS phenotype (28), defined by at least one of the following:
- High plasma levels of inflammatory biomarkers
- Vasopressor dependence
- Lower serum bicarbonate or increased serum lactate
-Informed consent expressed by the patient or by legal representative or on the Ethical Committee indication.

Concomitante presenza di:
1. ARDS (moderata e grave)
2. Fenotipo infiammatorio ARDS (28), definito da almeno uno dei seguenti fattori:
- Elevati livelli plasmatici di biomarcatori infiammatori
- Dipendenza da Vasopressori
- Basso siero bicarbonato o lattato di siero aumentato
3. Consenso informato espresso dal paziente o dal rappresentante legale o su indicazione del Comitato Etico

E.4

Principal exclusion criteria

1. Intubated and mechanically ventilated via an endotracheal or tracheostomy tube (>7 days) up to the time of randomization
2. ARDS severe or moderate for more than 36 hours
3. Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of ARF
4. ARF fully explained by left ventricular failure or fluid overload
5. Consent declined
6. Severe chronic respiratory disease requiring domiciliary ventilation
7. Clinical suspicion for significant restrictive lung disease
8. Pregnant women ore women of childbearing potential who are sexually active
9. Known allergy to pirfenidone
10.Concomitant use of fluvoxamine
11. Known severe hepatic failure
12. Known severe renal failure or necessity of dialysis not related to acute disease
13. Little chance of survival (SAPS II score>75)

1. Intubato e ventilato meccanicamente attraverso un tubo endotracheale o tracheostomico (>7 giorni) fino al momento della randomizzazione
2. ARDS grave o moderata per più di 36 ore
3. Embolia polmonare non trattata, versamento pleurico o pneumotoracico come causa primaria della ARF
4. ARF completamente spiegata da insufficienza ventricolare sinistra o sovraccarico di fluido
5. Il consenso è stato rifiutato
6. Grave malattia respiratoria cronica che richiede la ventilazione domiciliare
7. Sospetto clinico per una significativa malattia polmonare restrittiva
8. Donne incinte o donne in gravidanza o donne in età fertile che sono sessualmente attive
9. Allergia nota al pirfenidone
10. Uso concomitante di fluvoxamina
11. Conosciuta grave insufficienza epatica
12. Conosciuta grave insufficienza renale o necessità di dialisi.
13. Scarse possibilità di sopravvivenza (punteggio SAPS II>75)

E.5 End points

E.5.1

Primary end point(s)

To increase the number of ventilator free days at day 28 post randomization

Aumentare il numero dei giorni liberi da ventilazione meccanica a 28 giorni dalla randomizzazione

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 28 days

fino a 28 giorni

E.5.2

Secondary end point(s)

Death due to any cause, ICU-free days, SOFA score at day 28, hospital length of stay, respiratory function, quality of life, fibroproliferative changes, cardiac function. Analysis of profibrotic markers in BAL samples.

Morte dovuta a qualsiasi causa, giorni liberi da TI, punteggio SOFA al giorno 28, durata della degenza, funzionalità respiratoria, qualità della vita, cambiamenti fibroproliferativi, funzionalità cardiaca. Analisi di marcatori profibrotici in campioni di BAL

E.5.2.1

Timepoint(s) of evaluation of this end point

During hospitalization, 28, 60,180,360 days after randomization.

Durante il ricovero ospedaliero, 28, 60,180,360 giorni dalla randomizzazione.

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

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)

E.8.2.2

Placebo

Yes

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

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

Information not present in EudraCT

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

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.1.2.1

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

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 2021-06-07.

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients who are unconscious and unable to give consent

Pazienti incoscienti e incapaci di rilasciare il proprio consenso

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

130

F.4.2

For a multinational trial

F.4.2.1

In the EEA

130

F.4.2.2

In the whole clinical trial

130

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)

Standard clinical practice

Normale pratica clinica.

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

2021-08-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-15

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

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