Using Pirfenidone to prevent lung fibrosis in ARDS patients

Pirfenidone to Prevent Fibrosis in ARDS. A Randomized Controlled Trial - PIONEER

This study tests if the drug Pirfenidone can help prevent lung scarring in patients with Acute Respiratory Distress Syndrome (ARDS).

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Università Vita-Salute San Raffaele (Academic / other)
• Locations: 17 sites (Milan, MI and 16 other locations)
• Trial ID: NCT05075161 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of Pirfenidone, an antifibrotic drug, in patients with Acute Respiratory Distress Syndrome (ARDS). The study aims to determine if Pirfenidone can reduce the development of pulmonary fibrosis, a common complication following ARDS. Participants will be randomly assigned to receive either Pirfenidone or a placebo while being monitored for improvements in lung function and overall recovery. The trial focuses on patients who meet specific criteria for ARDS and have inflammatory characteristics.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have been diagnosed with moderate to severe ARDS within one week of a clinical insult.

Not a fit: Patients who have been intubated and mechanically ventilated for more than seven days or those with ARDS lasting longer than 36 hours may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the incidence of pulmonary fibrosis in ARDS patients, improving long-term outcomes.

How similar studies have performed: While other studies have explored treatments for ARDS, the use of Pirfenidone specifically for this condition is novel and has not been extensively tested in clinical settings.

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)

Where this trial is running

Milan, MI and 16 other locations

• IRCCS San Raffaele Scientific Institute — Milan, Mi, Italy (Recruiting)
• Ospedale Cesare Arrigo — Alessandria, Piedmont, Italy (Recruiting)
• Ospedale Santa Maria — Bari, Italy (Recruiting)
• ASST Spedali Civili di Brescia — Brescia, Italy (Recruiting)
• Ospedale San Giovanni di Dio - Azienda Ospedaliera Universitaria di Cagliari — Cagliari, Italy (Recruiting)
• Ospedale di Merano — Merano, Italy (Recruiting)
• Ospedale Uboldo di Cernusco sul Naviglio — Milan, Italy (Recruiting)
• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan, Italy (Recruiting)
• AOU Policlinico Paolo Giaccone — Palermo, Italy (Recruiting)
• Azienda Ospedaliero Universitaria Pisana — Pisa, Italy (Recruiting)
• AOU Pisana — Pisa, Italy (Recruiting)
• A.O.R San Carlo — Potenza, Italy (Recruiting)
• Fondazione PTV - Policlinico Tor Vergata — Rome, Italy (Recruiting)
• Azienda Ospedaliero Universitaria Senese — Siena, Italy (Recruiting)
• AOU Città della Salute e della Scienza — Torino, Italy (Recruiting)
• Azienda Sanitaria Universitaria Integrata di Udine — Udine, Italy (Recruiting)
• Astana Medical University — Astana, Kazakhstan (Recruiting)

Study contacts

• Study coordinator: Nora Di Tomasso, MD

Conditions Acute Respiratory Distress Syndrome; ARDS; Pulmonary Fibrosis; Mechanical Ventilation; Antifibrotic drug; Intensive Care Unit; ICU discharge; Mortality