Treatment With Pirfenidone for COVID-19 Related Severe ARDS

May 20, 2023 updated by: Yasmeen Abu Fraiha, Soroka University Medical Center

Treatment With Pirfenidone for COVID-19 Related Severe ARDS An Open Label Pilot Trial

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Be'er Sheva, Israel
        • Soroka Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Standard of Care - Control
Standard of care (Soc) according to current guidelines and the discretion of treating physician.
Other: Standard of care
Treatment with SoC as mentioned in the control arm description.
Other Names:
  • Control Arm
Experimental: Pirfenidone Treatment

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.
Drug: Pirfenidone
Treatment with Pirfenidone as mentioned in the experimental arm description.
Other Names:
  • Intervention Arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilation free days to day 28 (VFD28)
Time Frame: Up to 28 days from admission to ICU
Measured in number of days
Up to 28 days from admission to ICU
Severe adverse events (SAEs) rate
Time Frame: Through study completion, an average of 1 year
Number of SAEs divided to number of patients
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Through study completion, an average of 1 year
Includes all cause mortality, mortality in the ICU, 28 days mortality, 60 days mortality, in-hospital mortality, and ARDS related mortality. Measured in number of days.
Through study completion, an average of 1 year
ICU length of stay
Time Frame: Through study completion, an average of 1 year
Measured in number of days
Through study completion, an average of 1 year
Lung compliance
Time Frame: Through study completion, an average of 1 year
Part of mechanical ventilation parameters, calculated as tidal volume divided by the difference between plateau pressure and PEEP. Daily average will be assessed until extubation. Units are mL/cmH2O.
Through study completion, an average of 1 year
Tidal Volume
Time Frame: Through study completion, an average of 1 year
Part of mechanical ventilation parameters, it is the lung volume representing the volume of air displaced between normal inhalation and exhalation. Measured continuously by the ventilator, calculated and represented as area under the curve after omitting extreme values <5 and >95 percentiles. Measured in mL.
Through study completion, an average of 1 year
Positive End Expiratory Pressure (PEEP)
Time Frame: Through study completion, an average of 1 year
Part of mechanical ventilation parameters, it is the pressure in the lungs above atmospheric pressure that exists at the end of expiration. It is set by the treating physicians according to the clinical situation of the patient, and will be documented daily until extubation. Measured in cmH2O.
Through study completion, an average of 1 year
Driving Pressure
Time Frame: Through study completion, an average of 1 year
Part of mechanical ventilation parameters, it is the difference between plateau pressure and PEEP. Measured continuously by the ventilator, calculated and represented as area under the curve after omitting extreme values <5 and >95 percentiles.
Through study completion, an average of 1 year
Quality of life questionnaire
Time Frame: on admission and 6 months after discharge
Assessed by St George Respiratory Questionnaire (SGRQ). Scoring range from 0 to 100, with higher scored indicating more limitation.
on admission and 6 months after discharge
Vital Capacity (VC)
Time Frame: On admission (if possible) and 6 months after discharge
Part of pulmonary function tests, it is the maximum amount of air a person can expel from the lungs after a maximum inhalation. Measured on a spirometer in mL.
On admission (if possible) and 6 months after discharge
Forced Vital Capacity (FVC)
Time Frame: On admission (if possible) and 6 months after discharge
Part of pulmonary function tests, it is the vital capacity that results from a maximally forced expiratory effort. Measured on a spirometer in mL.
On admission (if possible) and 6 months after discharge
Forced Expiratory Volume at first second (FEV1)
Time Frame: On admission (if possible) and 6 months after discharge
Part of pulmonary function tests, it is the volume of air exhaled at the end of the first second of forced expiration. Measured on a spirometer in mL.
On admission (if possible) and 6 months after discharge
Diffusing Capacity for Carbon Monoxide (DLCO)
Time Frame: On admission (if possible) and 6 months after discharge
Part of pulmonary function tests, it is the extent to which oxygen passes from the air sacs of the lungs into the blood. Measured on a spirometer in mL/min/kPa.
On admission (if possible) and 6 months after discharge
6 minutes walking test
Time Frame: 6 months after discharge from hospital
The distance covered over a time of 6 minutes, measured in meters.
6 months after discharge from hospital

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Soroka University Medical Center

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Ori Galante, MD, ICU physician in SMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 8, 2020

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

October 27, 2020

First Submitted That Met QC Criteria

December 3, 2020

First Posted (Actual)

December 4, 2020

Study Record Updates

Last Update Posted (Actual)

May 23, 2023

Last Update Submitted That Met QC Criteria

May 20, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRC20007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Covid19

Clinical Trials on Standard of care

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Equatorial Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe