PIrfenidone to prevent fibrOsis in ARDS. A RaNdomizEd controllEd tRial - PIONEER

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-01-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514355-16-01

EudraCT number

2020-005306-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary outcome of this clinical trial is to document an increase in the number of ventilator free days (VFD) at day 28 in the Pirfenidone group when compared to the placebo group.

Secondary objectives 1

1. To reduce the duration of mechanical ventilation, the length of ICU stay and the rate of mechanical ventilation-related complications such as pneumonia.

Conditions and MedDRA coding

Acute Respiratory Distress Syndrome (ARDS)

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. ARDS (moderate and severe) based on the Berlin definition
2. Inflammatory ARDS phenotype as defined by at least one of the following: 1) High plasma levels of inflammatory biomarkers (e.g. IL-6 > 80 pg/ml, PCR > 250 mg/l); 2) Vasopressor dependence (any vasoconstrictor at any dosage for at least 1 hour); 3) Low serum bicarbonate (< 18 mmol/l) or increased serum lactate (>4 mmol/l)
3. Informed consent expressed by the patient or by his/her legal representative or on Ethical Committee indication

Exclusion criteria 14

1. Age < 18 years
2. Intubated and mechanically ventilated via an endotracheal or tracheostomy tube (>7 days) up to the time of randomization
3. ARDS severe or moderate for more than 36 hours
4. Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure (ARF)
5. ARF fully explained by left ventricular failure or fluid overload (determined by clinical assessment or echocardiography/cardiac output monitoring)
6. Consent declined
7. Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)
8. Clinical suspicion for significant restrictive lung disease (history of pulmonary fibrosis or suggestive pulmonary function tests)
9. Women of childbearing potential who are sexually active and in whom a pregnancy test is either not available or positive at the time of enrolment. Women who are surgically sterile or sterile for any other reason are eligible, after providing medical evidence and maintaining it in the study file. Women who are post-menopausal as evidenced by the absence of menstruation for at least 1 year are eligible; the date of the last menstruation is to be recorded in the study file unless postmenopausal status is obvious due to age
10. Known allergy to Pirfenidone
11. Concomitant use of Fluvoxamine
12. Known severe hepatic failure either chronic (defined as a Child Plug class C) or acute, defined as: AST/ALT elevation >3 and ≤5 x ULN and bilirubin > 2 mg/dl or clinical signs and symptoms of hepatic damage; or AST/ALT elevation >5 x ULN
13. Known severe renal failure (Cl-Creatinine less than 30 ml/min) either chronic or at the time of assessment; or necessity of dialysis either chronic or at the time of assessment
14. Little chance of survival, as defined by a SAPS II score more than 75 points

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome of this clinical trial is to document an increase in the number of ventilator free days (VFD) at day 28 in the Pirfenidone group when compared to the placebo group.

Secondary endpoints 11

1. Increase in ICU-free days at day 28
2. Increase in cumulative SOFA-free score at day 28
3. Reduction in hospital length of stay
4. Reduction in fibroproliferative changes on high-resolution CT performed at ICU discharge, according to specific interpretation guidelines
5. Mortality at ICU/hospital discharge
6. Better pulmonary function test (spirometry) at hospital discharge
7. Greater distance at the 6 minute walk test (at 6-12 months)
8. Better Quality of life as measured by EQ-5D Health Questionnaire and SF-36 questionnaire
9. Right and left heart dysfunction as determined by echocardiography at ICU discharge
10. Adverse event rate
11. Use of rescue therapies for severe hypoxaemia

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Nora Di Tomasso

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Giacomo Monti

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications