Back to resultsFX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia (FX-COVID)
Primary Purpose
Ards, Covid19, Pneumonia
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
FX06
Placebo of FX06
Sponsored by
About this trial
This is an interventional treatment trial for Ards focused on measuring FX06, Pulmonary vascular hyperpermeability
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- Service de Médecine Intensive Réanimation - CHU Angers
- Service de Médecine Intensive Réanimation - CHI de Poissy
- Hôpital Pitié Salpêtrière
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
FX06
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change in extravascular lung water index (EVLWi)
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
Evolution of daily extravascular lung water index (EVLWi)
measured by transpulmonary thermodilution during 7 days
Evolution of daily cardiac index
measured by transpulmonary thermodilution during 7 days
Evolution of global end-diastolic volume index
measured by transpulmonary thermodilution during 7 days
Evolution of pulmonary vascular permeability index
measured by transpulmonary thermodilution during 7 days
Overall survival
Mortality rate in ICU and in hospital
Rate of withdraw or withhold life-sustaining treatments decision
Daily weight
Daily fluid balance
Evolution of albuminemia
Evolution of blood biological criteria (g/L)
Duration of mechanical ventilation
Proportion of participants alive and off invasive mechanical ventilation
Evolution of Murray ARDS severity score
Evolution of radiological Weinberg score
Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity
Evolution of pulmonary Sequential Organ Failure Assessment) score.
Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease
Rate of rescue therapy with Veino-veinous V-ECMO
Evolution of SOFA (Sequential Organ Failure Assessment) score
Scale from 0 to 24, lower is better.
Organ failure free days
one or more SOFA sub-score >=3
Renal replacement therapy free days
Duration of renal replacement therapy free days
Nature and frequency of adverse events
Evolution of FX06 concentration
measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min
Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure
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.
Full Information
NCT ID
NCT04618042
First Posted
October 23, 2020
Last Updated
June 21, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04618042
Brief Title
FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Acronym
FX-COVID
Official Title
FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
November 13, 2020 (Actual)
Primary Completion Date
May 14, 2021 (Actual)
Study Completion Date
June 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ards, Covid19, Pneumonia
Keywords
FX06, Pulmonary vascular hyperpermeability
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FX06
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
FX06
Intervention Description
FX06 i.v.: 400 mg per day (divided in two injections) during 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo of FX06
Intervention Description
Placebo i.v.: 400 mg per day (divided in two injections) during 5 days
Primary Outcome Measure Information:
Title
Change in extravascular lung water index (EVLWi)
Description
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
Time Frame
Between Day 1 and Day 7
Secondary Outcome Measure Information:
Title
Evolution of daily extravascular lung water index (EVLWi)
Description
measured by transpulmonary thermodilution during 7 days
Time Frame
Between Day 1 and Day 7
Title
Evolution of daily cardiac index
Description
measured by transpulmonary thermodilution during 7 days
Time Frame
Between Day 1 and Day 7
Title
Evolution of global end-diastolic volume index
Description
measured by transpulmonary thermodilution during 7 days
Time Frame
Between Day 1 and Day 7
Title
Evolution of pulmonary vascular permeability index
Description
measured by transpulmonary thermodilution during 7 days
Time Frame
Between Day 1 and Day 7
Title
Overall survival
Time Frame
Day 30
Title
Mortality rate in ICU and in hospital
Time Frame
Through study completion an average of 2 months
Title
Rate of withdraw or withhold life-sustaining treatments decision
Time Frame
Day 30
Title
Daily weight
Time Frame
Between Day 1 and Day 7
Title
Daily fluid balance
Time Frame
Between Day 1 and Day 7
Title
Evolution of albuminemia
Description
Evolution of blood biological criteria (g/L)
Time Frame
Between Day 1 and Day 7
Title
Duration of mechanical ventilation
Time Frame
Day 30
Title
Proportion of participants alive and off invasive mechanical ventilation
Time Frame
Day 30
Title
Evolution of Murray ARDS severity score
Time Frame
Day 1 to day 15
Title
Evolution of radiological Weinberg score
Description
Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity
Time Frame
Day 1 to Day 30
Title
Evolution of pulmonary Sequential Organ Failure Assessment) score.
Description
Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease
Time Frame
Day 1 to day 15
Title
Rate of rescue therapy with Veino-veinous V-ECMO
Time Frame
Through study completion an average of 2 months
Title
Evolution of SOFA (Sequential Organ Failure Assessment) score
Description
Scale from 0 to 24, lower is better.
Time Frame
Day 15
Title
Organ failure free days
Description
one or more SOFA sub-score >=3
Time Frame
Day 15
Title
Renal replacement therapy free days
Time Frame
Day 30
Title
Duration of renal replacement therapy free days
Time Frame
Day 30
Title
Nature and frequency of adverse events
Time Frame
Through study completion an average of 2 months
Title
Evolution of FX06 concentration
Description
measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min
Time Frame
Day 1
Title
Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure
Description
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.
Time Frame
Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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)
Facility Information:
Facility Name
Service de Médecine Intensive Réanimation - CHU Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Service de Médecine Intensive Réanimation - CHI de Poissy
City
Chambourcy
ZIP/Postal Code
78240
Country
France
Facility Name
Hôpital Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Learn more about this trial
FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
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