Pirfenidone to Prevent Fibrosis in Ards.
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversità Vita-Salute San Raffaele
About this trial
Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury and a major cause of Intensive Care Unit (ICU) admission worldwide. Despite a large number of randomized clinical trials, a specific and effective pharmacological approach for patients with ARDS is still lacking.
Fibroproliferation is a crucial part of the host defence response, and severe fibrotic lung disease affects ARDS patients even years after acute phase resolution.
Pirfenidone is an oral anti-fibrotic drug, approved and largely used for treatment of idiopathic pulmonary fibrosis (IPF). The effect of Pirfenidone in ARDS has been evaluated only in animal models.
This is a randomized controlled study to evaluate for the first time the efficacy of Pirfenidone in ARDS.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
ARDS (moderate and severe) - Berlin definition
Within 1 week of a known clinical insult or new or worsening respiratory symptoms
Bilateral opacities on CXR which are not fully explained by effusions, lobar/lung collapse or nodules
Respiratory failure not fully explained by cardiac failure or fluid overload
Disqualifiers
Intubated and mechanically ventilated via an endotracheal or tracheostomy tube (>7 days) up to the time of randomization
ARDS severe or moderate for more than 36 hours
Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of ARF
ARF fully explained by left ventricular failure or fluid overload
Trial design
Design model
Parallel
Treatments tested in this trial
Pirfenidone
DrugFrom days 1-7: 801mg/day; from days 8-14:1602mg/day, from day 15 to ICU discharge 2403 mg/day. All drugs will be delivered by a nasogastric tube divided in 3 daily doses.
Placebo
DrugAll drugs will be delivered by a nasogastric tube divided in 3 daily doses.
Treatment groups
130 Participants
are divided into 2 treatment groupsGroup A: PirfenidoneExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
The number of ventilator free days (VFD) at day 28.
The primary outcome will be calculated following these rules: 1. the total number of days from day 1 to 28 post randomization on which a patient is alive and receives no assistance from mechanical ventilation, if any period of ventilator liberation lasts at least 48 consecutive hours. 2. study day 1 is the day of enrolment. 3. if patients are on mechanical ventilation they will be classified as being on mechanical ventilation for that entire study day. 4. to be considered liberated from mechanical ventilation, the patient will need to have at least 48 consecutive hours without mechanical ventilation. 5. non-invasive mechanical ventilation will not be considered assistance if it is provided by face or nasal mask. 6. patients dead before weaning will be allocated the value of 0 ventilator free days. Any patient who dies after weaning from mechanical ventilation but before day 28 will not have the days after their death until day 28 considered as a VFD.
Time frame
28 daysSecondary outcomes
1
ICU-free days at day 28
Number of days from randomization to day 28 (or death) in which the subject is outside the ICU. For any discharge lasting less than 48h, no ICU-free days will be computed. Re-admission lasting less than 24 hours will not reduce ICU-fd. Patients that will not survive outside ICU for at least 48 hours.
Time frame
28 days2
Cumulative SOFA-free point at day 28
Sequential organ failure assessment score to describe the extent of a patient's organ function and the rate of failure
Time frame
28 days3
Hospital length of stay.
The total number of days of hospital stay or until dead
Time frame
28 days or until discharge4
Fibroproliferative changes on high-resolution CT performed at ICU discharge
High-resolution CT (HRCT) scan will be performed at ICU discharge. HRCT scans will be evaluated by two independent observers - radiologists with experience and will be unaware of patient condition. According to specific interpretation guidelines, the presence and extent of areas of ground-glass attenuation, air-space consolidation, traction bronchiectasis, traction bronchiolectasis and honeycombing will be assessed. (Am J Respir Crit Care Med. 2017 May 1;195(9):1253-1263).
Time frame
28 days or until dischargeSponsors and contacts
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Source ClinicalTrials.gov