Acute Respiratory Distress Syndrome (ARDS)Phase 3PIONEERNCT05075161
Pirfenidone to Prevent Fibrosis in Ards.
A Phase 3 study testing Pirfenidone in people with Acute Respiratory Distress Syndrome (ARDS), run by Università Vita-Salute San Raffaele at 17 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome (ARDS)
- What is being tested?
- Pirfenidone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 1 Jun 2022to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Concomitant presence of:
- ARDS (moderate and severe) - Berlin definition
- Within 1 week of a known clinical insult or new or worsening respiratory symptoms
- Bilateral opacities on CXR which are not fully explained by effusions, lobar/lung collapse or nodules
- Respiratory failure not fully explained by cardiac failure or fluid overload
- PaO2/FiO2<200 mmHg with PEEP<=5 cmH2O (invasive mechanical ventilation)
Show all 12Show fewer
- Inflammatory ARDS phenotype (28), defined by at least one of the following:
- High plasma levels of inflammatory biomarkers
- Vasopressor dependence
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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)
Trial locations and contacts
17 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
17 sites in 2 countries
Italy16 sites, 16 recruiting
- Recruiting
Ospedale Cesare Arrigo
Alessandria, Piedmont, 15121
Giulia Maj, MD
Giulia Maj, MD, giulia.maj@ospedale.al.it
- Recruiting
Ospedale Santa Maria
Bari
Michele Gerardi
- Recruiting
ASST Spedali Civili di Brescia
Brescia, 25123
Matteo Filippini, MD, matteo.filippini123@gmail.com
- Recruiting
Ospedale San Giovanni di Dio - Azienda Ospedaliera Universitaria di Cagliari
Cagliari, 09123
Gabriele Finco, MD, gabriele.finco@gmail.com
- Recruiting
Ospedale di Merano
Merano
Simon Rauch, MD, simon.rauch@sabes.it
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, MI, 20132
Nora Di Tomasso, MD, +39022643 ext. 7722, ditomasso.nora@hsr.it
- Recruiting
Ospedale Uboldo di Cernusco sul Naviglio
Milan, 20070
Massimo Zambon, MD, massimo.zambon@asst-melegnano-martesana.it
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
Giacomo Grasselli
Alessio Caccioppola
- Recruiting
AOU Policlinico Paolo Giaccone
Palermo
Andrea Cortegiani, MD
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Fabio Guarracino, prof, fabioguarracino@gmail.com
- Recruiting
AOU Pisana
Pisa
Francesco Corradi, MD
- Recruiting
A.O.R San Carlo
Potenza
Gianluca Paternoster, MD, paternostergianluca@gmail.com
- Recruiting
Fondazione PTV - Policlinico Tor Vergata
Rome, 00133
Valentina Ajello, MD, valeajello@gmail.com
- Recruiting
Azienda Ospedaliero Universitaria Senese
Siena, 53100
Casere Biuzzi, prof, cesare.biuzzi@ao-siena.toscana.it
- Recruiting
AOU Città della Salute e della Scienza
Torino, 10126
Gabriele Sales, MD, gabriele.sales86@gmail.com
- Recruiting
Azienda Sanitaria Universitaria Integrata di Udine
Udine, 33100
Tiziana Bove, prof, tiziana.bove@asufc.sanita.fvg.it
Kazakhstan1 site, 1 recruiting
- Recruiting
Astana Medical University
Astana, 010000
Aidos Konkayev, Full Professor, +77475339215, konkaev@mail.ru
About this study
Official title: Pirfenidone to Prevent Fibrosis in ARDS. A Randomized Controlled Trial - PIONEER
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.
Read more
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.
Read the 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.
- Being tested
- Pirfenidone, Placebo
- Keywords
- ARDS, Pulmonary Fibrosis, Mechanical Ventilation, Antifibrotic drug, Intensive Care Unit, ICU discharge, Mortality, Spirometry, Quality of life
- Medical subject headings
- Respiratory Distress Syndrome, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
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.
PlaceboDrug
All drugs will be delivered by a nasogastric tube divided in 3 daily doses.
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone | Experimental | Patients randomized to Pirfernidone Group will receive tables of 267 mg Receives: Drug: Pirfenidone |
| Placebo | Placebo comparator | Patients randomized to Placebo Group will receive 5 ml of Water Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of ventilator free days (VFD) at day 28.
The primary outcome will be calculated following these rules:
- 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.
- study day 1 is the day of enrolment.
- if patients are on mechanical ventilation they will be classified as being on mechanical ventilation for that entire study day.
- to be considered liberated from mechanical ventilation, the patient will need to have at least 48 consecutive hours without mechanical ventilation.
- non-invasive mechanical ventilation will not be considered assistance if it is provided by face or nasal mask.
- 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.
Measured: 28 days
Secondary outcomes (12)
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.
Measured: 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
Measured: 28 days
Hospital length of stay.
The total number of days of hospital stay or until dead
Measured: 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).
Measured: 28 days or until discharge
Mortality at ICU/hospital discharge
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 28 days or until discharge
Adverse event rate
Number of patients who experience at least one adverse event and number of total adverse events
Measured: 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)
Measured: 28 days or until discharge
Broncoalveolar lavage fluid (BAL) speciments
Cell biology of pulmonary sputum or tissue
Measured: 28 days or until discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2021
- Study start1 Jun 2022
- Primary completionJun 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress Syndrome (ARDS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Vita-Salute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Landoni, Università Vita-Salute San Raffaele
- Investigators
- Giovanni Landoni, Professor, Study chair, Università Vita-Salute San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05075161
- Sponsor's protocol ID
- PIONEER
- Other IDs
- 2020-005306-25
- Acronym
- PIONEER
- Status last verified
- May 2026
- First submitted
- 25 May 2021
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
PubMed 22797452Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337Bos LD, Martin-Loeches I, Schultz MJ. ARDS: challenges in patient care and frontiers in research. Eur Respir Rev. 2018 Jan 24;27(147):170107. doi: 10.1183/16000617.0107-2017. Print 2018 Mar 31.
PubMed 29367411Gao Smith F, Perkins GD, Gates S, Young D, McAuley DF, Tunnicliffe W, Khan Z, Lamb SE; BALTI-2 study investigators. Effect of intravenous beta-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet. 2012 Jan 21;379(9812):229-35. doi: 10.1016/S0140-6736(11)61623-1. Epub 2011 Dec 11.
PubMed 22166903Davidson WJ, Dorscheid D, Spragg R, Schulzer M, Mak E, Ayas NT. Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis. Crit Care. 2006;10(2):R41. doi: 10.1186/cc4851.
PubMed 16542488Zhang Y, Ding S, Li C, Wang Y, Chen Z, Wang Z. Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: A meta-analysis. Exp Ther Med. 2017 Oct;14(4):2863-2868. doi: 10.3892/etm.2017.4891. Epub 2017 Aug 7.
PubMed 28928799Iwata K, Doi A, Ohji G, Oka H, Oba Y, Takimoto K, Igarashi W, Gremillion DH, Shimada T. Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis. Intern Med. 2010;49(22):2423-32. doi: 10.2169/internalmedicine.49.4010. Epub 2010 Nov 15.
PubMed 21088343Paine R 3rd, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, Thannickal VJ, Burnham EL, Brown MB, Hyzy RC. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med. 2012 Jan;40(1):90-7. doi: 10.1097/CCM.0b013e31822d7bf0.
PubMed 21926600Agrawal A, Zhuo H, Brady S, Levitt J, Steingrub J, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Matthay MA, Liu KD. Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials. Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15;303(8):L634-9. doi: 10.1152/ajplung.00195.2012. Epub 2012 Aug 3.
PubMed 22865551Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
PubMed 24853585Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
PubMed 27513822Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995 Apr;107(4):1062-73. doi: 10.1378/chest.107.4.1062.
PubMed 7705118Wang CY, Calfee CS, Paul DW, Janz DR, May AK, Zhuo H, Bernard GR, Matthay MA, Ware LB, Kangelaris KN. One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome. Intensive Care Med. 2014 Mar;40(3):388-96. doi: 10.1007/s00134-013-3186-3. Epub 2014 Jan 17.
PubMed 24435201Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
PubMed 10793162Orme J Jr, Romney JS, Hopkins RO, Pope D, Chan KJ, Thomsen G, Crapo RO, Weaver LK. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003 Mar 1;167(5):690-4. doi: 10.1164/rccm.200206-542OC. Epub 2002 Dec 18.
PubMed 12493646
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pirfenidone to Prevent Fibrosis in ARDS. A Randomized Controlled Trial - PIONEER
- ClinicalTrials.gov ID
- NCT05075161
- Acronym / sponsor ID
- PIONEER / PIONEER
- Keywords
- ARDS, Pulmonary Fibrosis, Mechanical Ventilation, Antifibrotic drug, Intensive Care Unit, ICU discharge, Mortality, Spirometry
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Università Vita-Salute San RaffaeleUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 12 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone | Experimental | Drug: PirfenidonePatients randomized to Pirfernidone Group will receive tables of 267 mg |
| Placebo | Placebo comparator | Drug: PlaceboPatients randomized to Placebo Group will receive 5 ml of Water |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ARDS (moderate and severe) - Berlin definition
- Inflammatory ARDS phenotype (28), defined by at least one of the following:
- Informed consent expressed by the patient or by legal representative or on the Ethical Committee indication.
- Age >=18 years
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PirfenidoneFrom 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. | Drug | Pirfenidone |
| PlaceboAll drugs will be delivered by a nasogastric tube divided in 3 daily doses. | Drug | Placebo |
Primary outcome
The number of ventilator free days (VFD) at day 28.
Time frame: 28 days
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.
12 secondary outcomes
ICU-free days at day 28
Time frame: 28 days
Cumulative SOFA-free point at day 28
Time frame: 28 days
Hospital length of stay.
Time frame: 28 days or until discharge
Fibroproliferative changes on high-resolution CT performed at ICU discharge
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 .
Time frame: through study completion, an average of 1 year
Quality of life assessment at follow-up (6 12 months) with EQ-5D score.
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 (%).
Time frame: 28 days or until discharge
Proportion of subjects who develop right and/or left heart dysfunction
Time frame: 28 days or until discharge
Adverse event rate
Time frame: 28 days or until discharge
Use of rescue therapies for severe hypoxaemia
Time frame: 28 days or until discharge
Broncoalveolar lavage fluid (BAL) speciments
Time frame: 28 days or until discharge
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Background: PubMed 22797452ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.
- Background: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Background: PubMed 29367411Bos LD, Martin-Loeches I, Schultz MJ. ARDS: challenges in patient care and frontiers in research. Eur Respir Rev. 2018 Jan 24;27(147):170107. doi: 10.1183/16000617.0107-2017. Print 2018 Mar 31.
- Background: PubMed 22166903Gao Smith F, Perkins GD, Gates S, Young D, McAuley DF, Tunnicliffe W, Khan Z, Lamb SE; BALTI-2 study investigators. Effect of intravenous beta-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet. 2012 Jan 21;379(9812):229-35. doi: 10.1016/S0140-6736(11)61623-1. Epub 2011 Dec 11.
- Background: PubMed 16542488Davidson WJ, Dorscheid D, Spragg R, Schulzer M, Mak E, Ayas NT. Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis. Crit Care. 2006;10(2):R41. doi: 10.1186/cc4851.
- Background: PubMed 28928799Zhang Y, Ding S, Li C, Wang Y, Chen Z, Wang Z. Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: A meta-analysis. Exp Ther Med. 2017 Oct;14(4):2863-2868. doi: 10.3892/etm.2017.4891. Epub 2017 Aug 7.
- Background: PubMed 21088343Iwata K, Doi A, Ohji G, Oka H, Oba Y, Takimoto K, Igarashi W, Gremillion DH, Shimada T. Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis. Intern Med. 2010;49(22):2423-32. doi: 10.2169/internalmedicine.49.4010. Epub 2010 Nov 15.
- Background: PubMed 21926600Paine R 3rd, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, Thannickal VJ, Burnham EL, Brown MB, Hyzy RC. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med. 2012 Jan;40(1):90-7. doi: 10.1097/CCM.0b013e31822d7bf0.
- Background: PubMed 22865551Agrawal A, Zhuo H, Brady S, Levitt J, Steingrub J, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Matthay MA, Liu KD. Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials. Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15;303(8):L634-9. doi: 10.1152/ajplung.00195.2012. Epub 2012 Aug 3.
- Background: PubMed 24853585Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
- Background: PubMed 27513822Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
- Background: PubMed 7705118Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995 Apr;107(4):1062-73. doi: 10.1378/chest.107.4.1062.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giovanni Landoni, Professor study chair
Università Vita-Salute San Raffaele
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pirfenidone in people with Acute Respiratory Distress Syndrome (ARDS), run by Università Vita-Salute San Raffaele at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Italy, Kazakhstan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nora Di Tomasso, MD (+39022643 ext. 7722, ditomasso.nora@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of ventilator free days (VFD) at day 28. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05075161, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.