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Treatment With Pirfenidone for COVID-19 Related Severe ARDS

Sponsor
Soroka University Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04653831
Collaborator
Roche Pharma AG (Industry)
26
Enrollment
1
Location
2
Arms
24.7
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
N/A

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 Design

Study Type:
Interventional
Actual Enrollment :
26 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
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 SoC alone (control arm).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 SoC alone (control arm).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Treatment With Pirfenidone for COVID-19 Related Severe ARDS An Open Label Pilot Trial
Actual Study Start Date :
Nov 8, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Ventilation free days to day 28 (VFD28) [Up to 28 days from admission to ICU]

      Measured in number of days

    2. Severe adverse events (SAEs) rate [Through study completion, an average of 1 year]

      Number of SAEs divided to number of patients

    Secondary Outcome Measures

    1. Mortality [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.

    2. ICU length of stay [Through study completion, an average of 1 year]

      Measured in number of days

    3. Lung compliance [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.

    4. Tidal Volume [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.

    5. Positive End Expiratory Pressure (PEEP) [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.

    6. Driving Pressure [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.

    7. Quality of life questionnaire [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.

    8. Vital Capacity (VC) [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.

    9. Forced Vital Capacity (FVC) [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.

    10. Forced Expiratory Volume at first second (FEV1) [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.

    11. Diffusing Capacity for Carbon Monoxide (DLCO) [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.

    12. 6 minutes walking test [6 months after discharge from hospital]

      The distance covered over a time of 6 minutes, measured in meters.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Soroka Medical Center Be'er Sheva Israel

    Sponsors and Collaborators

    • Soroka University Medical Center
    • Roche Pharma AG

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Yasmeen Abu Fraiha, Internal Medicine resident, MD, Soroka University Medical Center
    ClinicalTrials.gov Identifier:
    NCT04653831
    Other Study ID Numbers:
    • SCRC20007
    First Posted:
    Dec 4, 2020
    Last Update Posted:
    Jul 27, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Yasmeen Abu Fraiha, Internal Medicine resident, MD, Soroka University Medical Center
    Covid-19
    ARDS
    Pirfenidone
    Additional relevant MeSH terms:
    COVID-19
    Pirfenidone

    Study Results

    No Results Posted as of Jul 27, 2022