Pirfenidone to Prevent Fibrosis in Ards.

NCT ID: NCT05075161

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2025-12-31

Brief Summary

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury and a major cause of Intensive Care Unit (ICU) admission worldwide. Despite a large number of randomized clinical trials, a specific and effective pharmacological approach for patients with ARDS is still lacking.

Fibroproliferation is a crucial part of the host defence response, and severe fibrotic lung disease affects ARDS patients even years after acute phase resolution.

Pirfenidone is an oral anti-fibrotic drug, approved and largely used for treatment of idiopathic pulmonary fibrosis (IPF). The effect of Pirfenidone in ARDS has been evaluated only in animal models.

This is a randomized controlled study to evaluate for the first time the efficacy of Pirfenidone in ARDS.

Detailed Description

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury, associated with increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue.

ARDS represents 10.4% of total ICU admissions and 23.4% of all patients requiring mechanical ventilation and the hospital mortality rate remains as high as 40%.

Optimal care for patients with ARDS includes PEEP, muscle relaxation, protective ventilation, prone position, conservative fluid strategy.

Pharmacological interventions focused on dampening the pro-inflammatory response in the initial phase of ARDS, on reduction of pulmonary oedema and on improvement of repair mechanisms. Besides treatment with glucocorticosteroids, none of the other pharmacological interventions tested so far in clinical trials showed a significant reduction in morbidity and mortality.

Many ARDS patients survive the acute inflammation phase but develop remarkable pulmonary fibrosis. In hospital mortality is significantly lower (24%) than 1-y mortality after hospital discharge (41%) regardless of the etiology of ARDS. Although a protective ventilation strategy can improve short-term survival in ARDS subjects, there is no difference in pulmonary function compared with standard ventilation treatment up to 2 years after the acute-phase resolution.

Pulmonary fibrosis was observed in 53% of ventilated patients who had ARDS for five days and their mortality rate was 57% compared with 0% in patients without pulmonary fibrosis.

The purpose of this study is to provide a large multicenter RCT with an adequate size to explore the efficacy of Pirfenidone in ARDS patients.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pirfenidone

Patients randomized to Pirfernidone Group will receive tables of 267 mg

Group Type: EXPERIMENTAL

Pirfenidone

Intervention Type: DRUG

From days 1-7: 801mg/day; from days 8-14:1602mg/day, from day 15 to ICU discharge 2403 mg/day. All drugs will be delivered by a nasogastric tube divided in 3 daily doses.

Placebo

Patients randomized to Placebo Group will receive 5 ml of Water

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

All drugs will be delivered by a nasogastric tube divided in 3 daily doses.

Interventions

Pirfenidone

From days 1-7: 801mg/day; from days 8-14:1602mg/day, from day 15 to ICU discharge 2403 mg/day. All drugs will be delivered by a nasogastric tube divided in 3 daily doses.

Intervention Type: DRUG

Placebo

All drugs will be delivered by a nasogastric tube divided in 3 daily doses.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concomitant presence of:

• ARDS (moderate and severe) - Berlin definition

1. Within 1 week of a known clinical insult or new or worsening respiratory symptoms

2. Bilateral opacities on CXR which are not fully explained by effusions, lobar/lung collapse or nodules

3. Respiratory failure not fully explained by cardiac failure or fluid overload

4. PaO2/FiO2<200 mmHg with PEEP<=5 cmH2O (invasive mechanical ventilation)

• Inflammatory ARDS phenotype (28), defined by at least one of the following:

1. High plasma levels of inflammatory biomarkers

2. Vasopressor dependence

3. Lower serum bicarbonate or increased serum lactate

• Informed consent expressed by the patient or by legal representative or on the Ethical Committee indication.
• Age >=18 years

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università Vita-Salute San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Landoni

MD, Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Giovanni Landoni, Professor

Role: STUDY_CHAIR

Vita-Salute San Raffaele University

Locations

IRCCS San Raffaele Scientific Institute

Milan, MI, Italy

Site Status: RECRUITING

Ospedale Cesare Arrigo

Alessandria, Piedmont, Italy

Site Status: RECRUITING

Ospedale Santa Maria

Bari, , Italy

Site Status: RECRUITING

ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status: RECRUITING

Ospedale San Giovanni di Dio - Azienda Ospedaliera Universitaria di Cagliari

Cagliari, , Italy

Site Status: RECRUITING

Ospedale di Merano

Merano, , Italy

Site Status: RECRUITING

Ospedale Uboldo di Cernusco sul Naviglio

Milan, , Italy

Site Status: RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: RECRUITING

AOU Policlinico Paolo Giaccone

Palermo, , Italy

Site Status: RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status: RECRUITING

AOU Pisana

Pisa, , Italy

Site Status: RECRUITING

A.O.R San Carlo

Potenza, , Italy

Site Status: RECRUITING

Fondazione PTV - Policlinico Tor Vergata

Rome, , Italy

Site Status: RECRUITING

Azienda Ospedaliero Universitaria Senese

Siena, , Italy

Site Status: RECRUITING

AOU Città della Salute e della Scienza

Torino, , Italy

Site Status: RECRUITING

Azienda Sanitaria Universitaria Integrata di Udine

Udine, , Italy

Site Status: RECRUITING

Astana Medical University

Astana, , Kazakhstan

Site Status: RECRUITING

Countries

Italy; Kazakhstan

Central Contacts

Nora Di Tomasso, MD

Role: CONTACT

ditomasso.nora@hsr.it

+39022643 ext. 7722

Giacomo Monti, MD

Role: CONTACT

monti.giacomo@hsr.it

+39022643 ext. 2222

Facility Contacts

Nora Di Tomasso, MD

Role: primary

ditomasso.nora@hsr.it

+39022643 ext. 7722

Giulia Maj, MD

Role: primary

Giulia Maj, MD

Role: backup

giulia.maj@ospedale.al.it

Michele Gerardi

Role: primary

Matteo Filippini, MD

Role: primary

matteo.filippini123@gmail.com

Gabriele Finco, MD

Role: primary

gabriele.finco@gmail.com

Simon Rauch, MD

Role: primary

simon.rauch@sabes.it

Massimo Zambon, MD

Role: primary

massimo.zambon@asst-melegnano-martesana.it

Giacomo Grasselli

Role: primary

Alessio Caccioppola

Role: backup

Andrea Cortegiani, MD

Role: primary

Fabio Guarracino, prof

Role: primary

fabioguarracino@gmail.com

Francesco Corradi, MD

Role: primary

Gianluca Paternoster, MD

Role: primary

paternostergianluca@gmail.com

Valentina Ajello, MD

Role: primary

valeajello@gmail.com

Casere Biuzzi, prof

Role: primary

cesare.biuzzi@ao-siena.toscana.it

Gabriele Sales, MD

Role: primary

gabriele.sales86@gmail.com

Tiziana Bove, prof

Role: primary

tiziana.bove@asufc.sanita.fvg.it

Aidos Konkayev, Full Professor

Role: primary

konkaev@mail.ru

+77475339215

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Other Identifiers

2020-005306-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PIONEER

Identifier Type: -

Identifier Source: org_study_id