Pirfenidone to Prevent Fibrosis in Ards.

Last updated: August 5, 2025
Sponsor: Università Vita-Salute San Raffaele
Overall Status: Active - Recruiting

Phase

3

Condition

Lung Injury

Respiratory Failure

Acute Respiratory Distress Syndrome (Ards)

Treatment

Pirfenidone

Placebo

Clinical Study ID

NCT05075161
PIONEER
2020-005306-25
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Concomitant presence of:

  • ARDS (moderate and severe) - Berlin definition

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

  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 theEthical Committee indication.

  • Age >=18 years

Exclusion

Exclusion Criteria:

  • Intubated and mechanically ventilated via an endotracheal or tracheostomy tube (>7days) 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 causeof 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)

Study Design

Total Participants: 130
Treatment Group(s): 2
Primary Treatment: Pirfenidone
Phase: 3
Study Start date:
June 01, 2022
Estimated Completion Date:
December 31, 2025

Study 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.

Connect with a study center

  • IRCCS San Raffaele Scientific Institute

    Milan, MI 20132
    Italy

    Active - Recruiting

  • Ospedale Cesare Arrigo

    Alessandria, Piemonte 15121
    Italy

    Active - Recruiting

  • Ospedale Santa Maria

    Bari,
    Italy

    Active - Recruiting

  • ASST Spedali Civili di Brescia

    Brescia, 25123
    Italy

    Active - Recruiting

  • Ospedale San Giovanni di Dio - Azienda Ospedaliera Universitaria di Cagliari

    Cagliari, 09123
    Italy

    Active - Recruiting

  • Ospedale di Merano

    Merano,
    Italy

    Active - Recruiting

  • Ospedale Uboldo di Cernusco sul Naviglio

    Milan, 20070
    Italy

    Active - Recruiting

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milano,
    Italy

    Active - Recruiting

  • AOU Policlinico Paolo Giaccone

    Palermo,
    Italy

    Active - Recruiting

  • AOU Pisana

    Pisa,
    Italy

    Active - Recruiting

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, 56126
    Italy

    Active - Recruiting

  • A.O.R San Carlo

    Potenza,
    Italy

    Active - Recruiting

  • Fondazione PTV - Policlinico Tor Vergata

    Rome, 00133
    Italy

    Active - Recruiting

  • Azienda Ospedaliero Universitaria Senese

    Siena, 53100
    Italy

    Active - Recruiting

  • AOU Città della Salute e della Scienza

    Torino, 10126
    Italy

    Active - Recruiting

  • Azienda Sanitaria Universitaria Integrata di Udine

    Udine, 33100
    Italy

    Active - Recruiting

  • Astana Medical University

    Astana, 010000
    Kazakhstan

    Active - Recruiting

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