Treatment With Pirfenidone for COVID-19 Related Severe ARDS

The objective of the trial is to evaluate the safety and efficacy of treatment with Pirfenidone vs SoC in COVID-19 induced severe Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation.

Following initial diagnosis of COVID-19, severe ARDS patient will be admitted to a dedicated intensive care unit (ICU) at Soroka University Medical Center (Day 0). Upon admission, patients will be randomized according to 1:1 ratio to one of the trial arms and receive either Pirfenidone 2,403mg administered through nasogastric tube as 801mg TID (intervention arm) plus SoC or only SoC treatment (control arm).

Patients' vital signs (temperature, blood pressure, pulse rate per minute, breath rate per minute, oxygen saturation) urine output, ventilation settings, and respiratory parameters will be monitored according to SoC. Symptom will be captured daily from patients as well as adverse events (AEs) assessment and recording of the need for any supportive care during the period of ICU admission.

Inclusion criteria

• Men and women between the ages 18-80 years
• Diagnosis of COVID19 with severe ARDS (PaO2/FIO2 <150mmHg)
• Admission to the ICU and in need of mechanical ventilation
• Able to give informed consent according to local regulations. If the patient is unable to give written informed consent, the form will be read to them and their verbal consent will be documented. If the patient is sedated, an impartial ICU physician will approve eligibility.

Exclusion criteria

• Previous use of nintedanib or pirfenidone
• Administration of fluvoxamine 7 days prior to admission to ICU
• Severe hepatic impairment (liver enzymes and bilirubin>2 of normal upper limit, at day 0) or end stage liver disease
• Severe renal impairment (CrCl <30 ml/min) or end stage renal disease requiring dialysis
• Pregnancy
• Participation in any other clinical trial 30 days prior to enrollment