A Phase 3 interventional study of Pirfenidone and Placebo in Acute Respiratory Distress Syndrome (ARDS), sponsored by Università Vita-Salute San Raffaele. Recruiting at 17 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by Università Vita-Salute San Raffaele · Phase 3, Interventional, and Treatment
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.
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.
1,387 studies on the registry are indexed under Respiratory Distress Syndrome; 283 are open to participants now.
This study's planned enrollment of 130 is above the median of 60 across 822 interventional studies indexed under Respiratory Distress Syndrome.
Browse Respiratory Distress Syndrome studies →Università Vita-Salute San Raffaele is the lead sponsor of 85 studies on the registry; 33 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Concomitant presence of:
ARDS (moderate and severe) - Berlin definition
Inflammatory ARDS phenotype (28), defined by at least one of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients randomized to Pirfernidone Group will receive tables of 267 mg
Drug: Pirfenidone
Patients randomized to Placebo Group will receive 5 ml of Water
Drug: Placebo
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.
All drugs will be delivered by a nasogastric tube divided in 3 daily doses.
The number of ventilator free days (VFD) at day 28.
The primary outcome will be calculated following these rules: 1. the total number of days from day 1 to 28 post randomization on which a patient is alive and receives no assistance from mechanical ventilation, if any period of ventilator liberation lasts at least 48 consecutive hours. 2. study day 1 is the day of enrolment. 3. if patients are on mechanical ventilation they will be classified as being on mechanical ventilation for that entire study day. 4. to be considered liberated from mechanical ventilation, the patient will need to have at least 48 consecutive hours without mechanical ventilation. 5. non-invasive mechanical ventilation will not be considered assistance if it is provided by face or nasal mask. 6. patients dead before weaning will be allocated the value of 0 ventilator free days. Any patient who dies after weaning from mechanical ventilation but before day 28 will not have the days after their death until day 28 considered as a VFD.
Time frame: 28 days
ICU-free days at day 28
Number of days from randomization to day 28 (or death) in which the subject is outside the ICU. For any discharge lasting less than 48h, no ICU-free days will be computed. Re-admission lasting less than 24 hours will not reduce ICU-fd. Patients that will not survive outside ICU for at least 48 hours.
Time frame: 28 days
Cumulative SOFA-free point at day 28
Sequential organ failure assessment score to describe the extent of a patient's organ function and the rate of failure
Time frame: 28 days
Hospital length of stay.
The total number of days of hospital stay or until dead
Time frame: 28 days or until discharge
Fibroproliferative changes on high-resolution CT performed at ICU discharge
High-resolution CT (HRCT) scan will be performed at ICU discharge. HRCT scans will be evaluated by two independent observers - radiologists with experience and will be unaware of patient condition. According to specific interpretation guidelines, the presence and extent of areas of ground-glass attenuation, air-space consolidation, traction bronchiectasis, traction bronchiolectasis and honeycombing will be assessed. (Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263).
Time frame: 28 days or until discharge
Mortality at ICU/hospital discharge
Time frame: 28 days or until discharge
Quality of life assessment at follow-up (6 12 months) with SF-36 .
The SF-36 assesses health across eight dimensions using 36 items, such as physical functioning, social functioning and vitality. The SF-36 produces one reported score on a 0-100 scale from the combination of different measurements.
Time frame: through study completion, an average of 1 year
Quality of life assessment at follow-up (6 12 months) with EQ-5D score.
The EQ-5D is the most widely used generic preference- based measure of health-related quality of life. It is based on five dimension (mobility, self-care, usual activity, pain/discomfort and anxiety/depression) and 3 levels (no problems, some problems, extreme problems)which combined, create 243 potential health states.
Time frame: through study completion, an average of 1 year
Percentage change in the spirometric values, such as FEV1 (% and L/min), FVC (% and L/min) and DLCO (%).
FEV1-Forced expiratory volume in one second; the volume of air exhaled in the first second under force after a maximal inhalation. It will be used as a baseline pulmonary function parameter. It will be performed via standard office spirometry. It will be calculated as an absolute value (in liters) and as a percentage (compared to the normal population data) FVC- Forced Vital Capacity; the total volume of air that can be exhaled during a maximal forced expiration effort. It will be calculated as an absolute value (in liters) and as a percentage (compared to the normal population data) DLCO-Diffusion Lung Carbon monOxide. It describes the lung capacity of gas exchange.
Time frame: 28 days or until discharge
Proportion of subjects who develop right and/or left heart dysfunction
Percentage change in the echocardiographic parameters from the baseline to the discharge. Tricuspid regurgitation (scored from 1 to 4) in the absence of organic tricuspid valve pathology. Tricuspid annular plane systolic excursion (TAPSE), reflects longitudinal shortening of the RV, measured in mm. Tissue doppler Index-S' (TDI) reflects the longitudinal velocity of the tricuspid annulus during systole. Measured in cm/sec. Pulmonary artery systolic pressure (PAPs) has a reasonable accuracy to diagnose exercise-induced pulmonary hypertension. Measured in mmHg. Telediastolic Diameter (TDD) meaning the measurement of the internal diameter of left ventricle in diastole. Measured in mm. Ejection Fraction (EF) calculated by dividing the volume of blood pumped from the left ventricle per beat, by the volume of blood collected in the left ventricle at the end of diastolic filling. Regional Wall Motion Abnormalities (RWMA)
Time frame: 28 days or until discharge
Adverse event rate
Number of patients who experience at least one adverse event and number of total adverse events
Time frame: 28 days or until discharge
Use of rescue therapies for severe hypoxaemia
Inhaled nitric oxide, inhaled prostacyclin, prone position, high frequency oscillatory ventilation and extracorporeal membrane ventilation (ECMO)
Time frame: 28 days or until discharge
Broncoalveolar lavage fluid (BAL) speciments
Cell biology of pulmonary sputum or tissue
Time frame: 28 days or until discharge
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