pirfenidone for Acute Respiratory Distress Syndrome (ARDS)

Inclusion criteria

• {"criterion_text":"- ARDS (moderate and severe) based on the Berlin definition"}
• {"criterion_text":"- Inflammatory ARDS phenotype as defined by at least one of the following: 1) High plasma levels of inflammatory biomarkers (e.g. IL-6 > 80 pg/ml, PCR > 250 mg/l); 2) Vasopressor dependence (any vasoconstrictor at any dosage for at least 1 hour); 3) Low serum bicarbonate (< 18 mmol/l) or increased serum lactate (>4 mmol/l)"}
• {"criterion_text":"- Informed consent expressed by the patient or by his/her legal representative or on Ethical Committee indication"}

Exclusion criteria

• {"criterion_text":"- Age < 18 years"}
• {"criterion_text":"- Intubated and mechanically ventilated via an endotracheal or tracheostomy tube (>7 days) up to the time of randomization"}
• {"criterion_text":"- ARDS severe or moderate for more than 36 hours"}
• {"criterion_text":"- Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure (ARF)"}
• {"criterion_text":"- ARF fully explained by left ventricular failure or fluid overload (determined by clinical assessment or echocardiography/cardiac output monitoring)"}
• {"criterion_text":"- Consent declined"}
• {"criterion_text":"- Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)"}
• {"criterion_text":"- Clinical suspicion for significant restrictive lung disease (history of pulmonary fibrosis or suggestive pulmonary function tests)"}
• {"criterion_text":"- Women of childbearing potential who are sexually active and in whom a pregnancy test is either not available or positive at the time of enrolment. Women who are surgically sterile or sterile for any other reason are eligible, after providing medical evidence and maintaining it in the study file. Women who are post-menopausal as evidenced by the absence of menstruation for at least 1 year are eligible; the date of the last menstruation is to be recorded in the study file unless postmenopausal status is obvious due to age"}
• {"criterion_text":"- Known allergy to Pirfenidone"}
• {"criterion_text":"- Concomitant use of Fluvoxamine"}
• {"criterion_text":"- Known severe hepatic failure either chronic (defined as a Child Plug class C) or acute, defined as: AST/ALT elevation >3 and ≤5 x ULN and bilirubin > 2 mg/dl or clinical signs and symptoms of hepatic damage; or AST/ALT elevation >5 x ULN"}
• {"criterion_text":"- Known severe renal failure (Cl-Creatinine less than 30 ml/min) either chronic or at the time of assessment; or necessity of dialysis either chronic or at the time of assessment"}
• {"criterion_text":"- Little chance of survival, as defined by a SAPS II score more than 75 points"}

Primary endpoints

• {"endpoint_text":"- The primary outcome of this clinical trial is to document an increase in the number of ventilator free days (VFD) at day 28 in the Pirfenidone group when compared to the placebo group.","definition_or_measurement_approach":"Number of ventilator-free days (VFD) measured at day 28 post-randomization; comparison of VFD between pirfenidone arm and placebo arm."}

Secondary endpoints

• {"endpoint_text":"- Increase in ICU-free days at day 28","definition_or_measurement_approach":"ICU-free days measured at day 28."}
• {"endpoint_text":"- Increase in cumulative SOFA-free score at day 28","definition_or_measurement_approach":"Cumulative SOFA-free score assessed up to day 28."}
• {"endpoint_text":"- Reduction in hospital length of stay","definition_or_measurement_approach":"Hospital length of stay measured (days) and compared between arms."}
• {"endpoint_text":"- Reduction in fibroproliferative changes on high-resolution CT performed at ICU discharge, according to specific interpretation guidelines","definition_or_measurement_approach":"High-resolution CT at ICU discharge evaluated according to predefined interpretation guidelines to assess fibroproliferative changes."}
• {"endpoint_text":"- Mortality at ICU/hospital discharge","definition_or_measurement_approach":"Mortality status at ICU and hospital discharge."}
• {"endpoint_text":"- Better pulmonary function test (spirometry) at hospital discharge","definition_or_measurement_approach":"Spirometry measurements at hospital discharge."}
• {"endpoint_text":"- Greater distance at the 6 minute walk test (at 6-12 months)","definition_or_measurement_approach":"6-minute walk test distance measured at 6–12 months post-randomization."}
• {"endpoint_text":"- Better Quality of life as measured by EQ-5D Health Questionnaire and SF-36 questionnaire","definition_or_measurement_approach":"Quality of life assessed using EQ-5D and SF-36 questionnaires."}
• {"endpoint_text":"- Right and left heart dysfunction as determined by echocardiography at ICU discharge","definition_or_measurement_approach":"Echocardiographic assessment of right and left heart function at ICU discharge."}
• {"endpoint_text":"- Adverse event rate","definition_or_measurement_approach":"Rate and incidence of adverse events collected during study period."}
• {"endpoint_text":"- Use of rescue therapies for severe hypoxaemia","definition_or_measurement_approach":"Use of specified rescue therapies for severe hypoxaemia recorded during ICU stay."}

Italy

Earliest CTIS Part Ii Submission Date

06-12-2024

Latest Decision Or Authorization Date

08-01-2025

Processing Time Days

33

Number Of Sites

30

Number Of Participants

100

Primary sponsor

Full Name

Ospedale San Raffaele S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy