Acute Respiratory Distress Syndrome (ARDS)
Conditions
Interventions
Product Name: Depelestat
Product Code: EPI-hNE4 and DX-890
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DEPELESTAT
Current Sponsor code: EPIhNE4 DX-890
Other descriptive
Sponsors
Debiopharm SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A) Patients suffering from persistent ARDS defined as follows : ARDS defined by: - acute respiratory failure on invasive or non invasive ventilation - bilateral pulmonary infiltrates on the chest X-ray, with a picture compatible with a pulmonary edema - Pa02/FI02 ratio of less than or equal to 200 mm Hg - no sign of left atrial hypertension (congestive heart failure) Persistence defined by: - Pa02/FI02 ratio of less than or equal to 200 mm Hg under invasive ventilation, with a PEEP level of higher than or equal to 5 cm H2O, 12 to 24 hours after the ARDS criteria were met (under invasive mechanical ventilation), as defined by the French Conference Consensus B) Predicted body weight less than or equal to 90 kg : predicted body weight of male patients is calculated as equal to 50 + 0.91 (cms of height – 152.4); that of female patients as equal to 45.5 + 0.91 (cms of height – 152.4) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - positive pregnancy test in woman of childbearing potential - patients suffering from pulmonary emphysema before ARDS occurred, with a TLC value higher than 130 % predicted - patients suffering from pulmonary fibrosis before ARDS occurred, with a TLC value less than or equal to 70 % predicted - patients with ARDS secondary to traumatism - patients suffering from ALI with a Pa02/FI02 ratio of less than or equal to 300 mm Hg under non invasive or invasive ventilation, for more than 24 hours before ARDS criteria were met - patients who are moribund and not expected to survive for more than 72 hours - patients suffering from a lung pneumocystosis - patients with a bronchopleural fistula - patients having received a systemic corticosteroid treatment at a dose higher than or equal to 0.5 mg/kg prednisolone for more than 2 weeks before inclusion - patients whose family or physician are not committed to aggressive support for more than 72 hours - patients with Pa02/FI02 less than or equal to 80 mm Hg, whatever the level of PEEP, contraindicating the BAL - patients with severe organ diseases : (a) renal failure : specific renal SOFA score = 4 or under dialysis (b) cardiovascular failure : severe hemodynamic instability graded III by Jardin score, with persistent of metabolic acidosis, defined as a base deficit of > 5 mmol/L present for > 6 hours, despite administration of vasoactive drugs (c) hepatic failure: specific hepatic SOFA score = 4 or Child-Pugh score class C (d)neutropenia: blood neutrophil count < 1000/mm3, or neutropenia expected because of ongoing cytostatic treatment (e) patients having received a bone marrow transplantation - patients already included in another therapeutical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of Depelestat administered by IV route in critically ill patients suffering from persistent ARDS To assess efficacy of Depelestat on prevention and treatment of alveolar inflammation by measuring relevant biological parameters in blood and BAL of ARDS patients To assess efficacy of Depelestat on prevention of early pulmonary fibrosis in ARDS patients, by assaying biological markers of lung collagen turnover in BAL and by measuring static compliance of the respiratory system. ;Secondary Objective: To assess the effect of Depelestat on the evolution of the clinical status of ARDS patients : - oxygenation by measuring Pa02/FI02 ratio - multi-organ dysfunction - ventilation-free days - mortality To assess basic pharmacokinetics in ARDS patients;Primary end point(s): A) Safety criteria - Incidence of adverse events - Change in vital signs - Change in safety blood chemistry and haematology parameters from "pre-treatment" to "during treatment" at 96 ± 24 hours, after initiation of infusion, to "post-treatment" at 48 ± 24 hours after the end of infusion, and to Day 28 or ICU discharge - Incidence of nosocomial infections during the study period from Day 1 to Day 28 - Incidence of barotraumatisms (pneumothorax) during the period of mechanical ventilation - Evolution of organs failure assessed by global and specific SOFA scores change from "pre-treatment" to "during treatment", and from "pre-treatment" to "post treatment", and from "pre-treatment" to Day 28 or ICU discharge - Anti-Depelestat antibodies plasma levels from "pre-treatment" to "post treatment" and to Day 28 or ICU discharge B) Primary efficacy criteria - Static compliance "last on treatment", measured under PEEP, on the inflation curve - Static compliance relative change from "pre-treatment" to "last on treatment", measured under PEEP, on the inflation curve | — |
Countries
Belgium, Italy, Spain
Outcome results
None listed