Treatment With Pirfenidone for COVID-19 Related Severe ARDS

Soroka University Medical Center

Status: Completed

Conditions: Covid19; ARDS

Treatments: Drug: Pirfenidone; Other: Standard of care

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04653831

SCRC20007

Details and patient eligibility

About

A randomized, open label, two arm, pilot trial of Pirfenidone 2,403 mg administered per nasogastric tube or orally as 801mg TID for 4 weeks in addition to Standard of Care (SoC), compared to SoC alone, in a population of COVID-19 induced severe ARDS. Patients will be randomized according to 1:1 ratio to one of the trial arms: Pirfenidone (intervention arm) or SoC (control arm).

Full description

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Standard of Care - Control

Other group

Description:

Standard of care (Soc) according to current guidelines and the discretion of treating physician.

Treatment:

Other: Standard of care

Pirfenidone Treatment

Experimental group

Description:

In addition to SoC, Pirfenidone 2,403 mg administered orally or per nasogastric tube as 801mg TID, for 4 weeks. Pirfenidone dose will be 2,403mg daily, from day one of admission to the ICU, titrated over 3 days: Day 1 - 801mg x 1/d (801mg) Day 2 - 801mg x 2/d (1,602 mg) Day 3 - 801mg x 3/d (2,403 mg) Feeding and medication delivery will be upon the discretion of the treating physician according to tolerability. Powdered 801mg tablets will be administered through the nasogastric tube: Each tablet will be crushed and dissolved in 20cc of water. The nasogastric tube will be flushed afterwards to avoid obstruction.. If the patient is able to swallow and the nasogastric tube is removed, pirfenidone will continue to be delivered orally.

Treatment:

Drug: Pirfenidone