ARDS, Covid19
Conditions
Keywords
Covid-19, ARDS, Pirfenidone
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).
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.
Interventions
DRUGPirfenidone
Treatment with Pirfenidone as mentioned in the experimental arm description.
OTHERStandard of care
Treatment with SoC as mentioned in the control arm description.
Sponsors
Roche Pharma AG
Soroka University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ventilation free days to day 28 (VFD28) | Up to 28 days from admission to ICU | Measured in number of days |
| Severe adverse events (SAEs) rate | Through study completion, an average of 1 year | Number of SAEs divided to number of patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU length of stay | Through study completion, an average of 1 year | Measured in number of days |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 6 minutes walking test | 6 months after discharge from hospital | The distance covered over a time of 6 minutes, measured in meters. |
| 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. |
| 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. |
Countries
Israel
Outcome results
None listed