Pirfenidone to Prevent Fibrosis in Ards.

• Status: Not yet recruiting
• Trial end date: 2025-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Università Vita-Salute San Raffaele
• Treatments: Pirfenidone

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)