Patients admitted in participating ICUs who received mechanical ventilation for SARS-CoV-2 induced acute respiratory distress syndrome (ARDS)
Conditions
Interventions
Product Name: FX06
Product Code: FX06
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Human Fibrinopeptide Bß15-42
Other descriptive name: FX06
Concentration unit: mg/ml milligram(s)/
Sponsors
Assistance Publique -Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. SARS-CoV-2 induced pneumonia confirmed by a positive PCR test in nasopharyngeal swab or respiratory tract secretions 3. Acute respiratory distress syndrome (ARDS) according to Berlin criteria (bilateral pulmonary infiltrates on frontal chest x-ray, PaO2/FiO2 ratio =300 mmHg, objective assessment excluding hydrostatic pulmonary oedema) 4. Need for endotracheal intubation and mechanical ventilation 5. Informed consent by patient or legal representative According to the specifications of emergency consent, randomization without the close relative or surrogate consent could be performed. 6. Affiliated to a social security system 7. Highly effective method of contraception (oral contraception associated with inhibition of ovulation, intrauterine device or hormone releasing system, bilateral tubal occlusion, vasectomized partner or sexual abstinence for more than three months before inclusion) and negative highly sensitive pregnancy test, for women of childbearing potential 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 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Mechanically ventilation for more than 4 days 2. Patient receiving drugs interfering with inflammation: non-steroidal anti-inflammatory drugs, immunoglobulins. 3. Patients receiving chemotherapy, radiotherapy or immunotherapy for malignancy 4. Participation in another interventional clinical trial 5. Women pregnant or lactating 6. Patient moribund on the day of randomization, defined by a SAPS-II score>90 7. Contra-indication for vascular access implantation for transpulmonary thermodilution monitoring 8. Severe or terminal renal insufficiency (creatinine clearance 2) 10. Severe cardiac insufficiency, with left ventricular ejection fraction<30% 11. Any history of severe allergic drug reaction (anaphylactic shock or allergic angioedema) 12. Persons deprived of their liberty by a judicial or administrative decision (guardianship or tutelage measure)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: FX06 infusion in conjunction with optimal medical treatment during SARS-CoV-2 induced ARDS reduces pulmonary vascular hyperpermeability at 7 days, compared to optimal medical treatment alone.;Secondary Objective: Secondary objectives will be to test the hypothesis that FX06 infusion: - improves mortality at 30 days following randomization - reduces capillary leak (weight, fluid balance, systolic, diastolic, mean blood pressure, heart rate, catecholamine and lactate clearance) - improves pulmonary recovery - improves the evolution of organ failure - reduces the need for hemodynamic support with catecholamines - reduces the need for renal dialysis The study will also evaluate determine • the tolerance of FX06 • its pharmacokinetic • PK/PD parameters of the drug • Immunogenicity induced by the drug ;Primary end point(s): Change in extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution between D1 and Day 7 after inclusion. Transpulmonary thermodilution systems, part of the standard management in ICU, allow a direct evaluation of vascular hyperpermeability in the lungs. Extra-vascular lung water index (EVLWi) is a reliable parameter, independently associated with mortality during ARDS [2]. ;Timepoint(s) of evaluation of this end point: Day 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Evolution of daily extravascular lung water index (EVLWi), cardiac index, global end-diastolic volume index, pulmonary vascular permeability index, measured by transpulmonary thermodilution during 7 days. - Overall survival at 30 days - Mortality rate in ICU, in hospital - Rate of withdraw or withhold life-sustaining treatments decision at Day 30 - Vascular leak: • Daily weight until D7 (% of D1) • Daily fluid balance until D7 • Evolution of albuminemia until D7 - Pulmonary recovery: • Duration of mechanical ventilation (MV) and MV free days at D30 • Ventilator-free survival (proportion of participants alive and off invasive mechanical ventilation) at D30 • PaO2/FiO2 and Murray ARDS severity score over 15 days • Evolution of pulmonary SOFA score over 15 days • Evolution of radiological Weinberg score over 30 days, analysed by a specialized radiologist, blinded for the treatment group • Rate of rescue therapy with VV-ECMO - Evolution of daily sequential organ failure score (SOFA) and organ failure (one or more SOFA sub-score =3) failure free days at D15 - Hemodynamic parameters • systolic, diastolic, mean blood pressure, heart rate twice a day during 7 days • lactate clearance, measured once a day during 7 days • catecholamine-free days at D30 - Duration of renal replacement therapy (RRT), and RRT free days at D30 - Nature and frequency of adverse events - Evolution of FX06 concentration from H0 to H1, measured at time 0 (before FX06 application) and after 5, 15, 30, 60 min - PK/PD analysis will be performed from those dosages, with a reduction of EVLWi of more than 30% before and 3 hours after injection as primary PD endpoint - Immunogenicity of the drug will be tested at day 7, according to manufacturer’s procedure ;Timepoint(s) of evaluation of this end point: D30 | — |
Countries
France
Contacts
Public ContactCarla VANDENABELE
Assistance Publique -Hôpitaux de Paris
Outcome results
None listed