FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
- Registration Number
- NCT04618042
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
Vascular leakage following endothelial injury, responsible for interstitial and alveolar edema, is a major feature of pathogen induced acute lung injury. As acute respiratory distress syndrome (ARDS) due to pandemic Covid-19 is associated with more than 60% mortality, controlling vascular leakage may be a major target to decrease the mortality associated with the spreading of the disease in France.
FX06, a drug under clinical development containing fibrin-derived peptide beta15-42, is able to stabilize cell-cell interactions, thereby reducing vascular leak and mortality in several animal models, particularly during lipopolysaccharide-induced and dengue hemorrhagic shock . A phase I study was conducted in humans, with no specific adverse event detected with a dose up to 17.5 mg/kg. In a phase II randomized multicentre double-blinded trial in 234 patients suffering from ST+ acute coronary syndrome, FX06 treated patients exhibited a 58% decrease in the early necrotic core zone. Importantly, adverse events were highly comparable between groups, indicating a high safety profile for the drug . Lastly, the drug was used as a salvage therapy in a patient exhibiting a severe ARDS following EBOLA virus infection . Altogether, those data indicate that FX06 is well tolerated in humans and is a potent regulator of vascular leakage.
Our hypothesis here is that FX06 may decrease pulmonary vascular hyperpermeability during ARDS following SARS-CoV-2 infection, thereby improving gas exchanges and the outcome of infected patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- Age ≥ 18 years
- SARS-CoV-2 induced pneumonia confirmed by a positive PCR test in nasopharyngeal swab or respiratory tract secretions and ≤ 85 years
- 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 edema)
- Need for endotracheal intubation and mechanical ventilation
- 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.
- Affiliated to a social security system
- Highly effective method of contraception and negative highly sensitive pregnancy test, for women of childbearing potential
- Mechanically ventilation for more than 4 days
- Patient receiving drugs interfering with inflammation: Non-steroidal anti-inflammatory drugs, immunoglobulins.
- Patients receiving chemotherapy, radiotherapy or immunotherapy for malignancy
- Participation in another interventional clinical trial
- Pregnant or lactating women
- Patient moribund on the day of randomization, defined by a SAPS-II score>90
- Contra-indication for vascular access implantation for transpulmonary thermodilution monitoring
- Severe or terminal renal insufficiency (creatinine clearance <30 ml/min)
- Severe hepatic insufficiency (hepatic SOFA score>2)
- Severe cardiac insufficiency, with left ventricular ejection fraction<30%
- Any history of severe allergic drug reaction (anaphylactic shock or allergic angioedema)
- Persons deprived of their liberty by a judicial or administrative decision (guardianship or tutelage measure)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo of FX06 - FX06 FX06 -
- Primary Outcome Measures
Name Time Method Change in extravascular lung water index (EVLWi) Between Day 1 and Day 7 Assessed by transpulmonary thermodilution Transpulmonary thermodilution systems, part of the standard management in ICU, allow a direct evaluation of vascular hyperpermeability in the lungs using thermodilution technique. EVLWi is a reliable parameter, independently associated with mortality during ARDS
- Secondary Outcome Measures
Name Time Method Evolution of daily extravascular lung water index (EVLWi) Between Day 1 and Day 7 measured by transpulmonary thermodilution during 7 days
Mortality rate in ICU and in hospital Through study completion an average of 2 months Proportion of participants alive and off invasive mechanical ventilation Day 30 Organ failure free days Day 15 one or more SOFA sub-score \>=3
Evolution of radiological Weinberg score Day 1 to Day 30 Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity
Evolution of pulmonary vascular permeability index Between Day 1 and Day 7 measured by transpulmonary thermodilution during 7 days
Rate of withdraw or withhold life-sustaining treatments decision Day 30 Evolution of FX06 concentration Day 1 measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min
Duration of renal replacement therapy free days Day 30 Daily weight Between Day 1 and Day 7 Duration of mechanical ventilation Day 30 Evolution of daily cardiac index Between Day 1 and Day 7 measured by transpulmonary thermodilution during 7 days
Evolution of global end-diastolic volume index Between Day 1 and Day 7 measured by transpulmonary thermodilution during 7 days
Overall survival Day 30 Daily fluid balance Between Day 1 and Day 7 Evolution of albuminemia Between Day 1 and Day 7 Evolution of blood biological criteria (g/L)
Evolution of pulmonary Sequential Organ Failure Assessment) score. Day 1 to day 15 Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease
Renal replacement therapy free days Day 30 Evolution of Murray ARDS severity score Day 1 to day 15 Rate of rescue therapy with Veino-veinous V-ECMO Through study completion an average of 2 months Evolution of SOFA (Sequential Organ Failure Assessment) score Day 15 Scale from 0 to 24, lower is better.
Nature and frequency of adverse events Through study completion an average of 2 months Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure Day 7 A test for immunogenicity will be performed on a serum sample at day 7 (2 days after the end of treatment administration) to detect any antibody against FX06. The assay will consist in a three-fold procedure, as recommended by the manufacturer. An initial screening assay will qualitatively measure antibodies to FX06. Samples deemed positive will be subject to a confirmatory assay, which will determine the specificity of the detected antibody against FX06. The third tier of the assay will consist in titre analysis to semi-quantitatively assess the antibody response.
Trial Locations
- Locations (3)
Service de Médecine Intensive Réanimation - CHI de Poissy
🇫🇷Chambourcy, France
Service de Médecine Intensive Réanimation - CHU Angers
🇫🇷Angers, France
Hôpital Pitié Salpêtrière
🇫🇷Paris, France