FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Change in extravascular lung water index (EVLWi)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
FX06
干预措施: FX06 (Drug)
Placebo
干预措施: Placebo of FX06 (Drug)
结局指标
主要结局
Change in extravascular lung water index (EVLWi)
时间窗: 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
次要结局
- Evolution of daily extravascular lung water index (EVLWi)(Between Day 1 and Day 7)
- 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)
- Evolution of radiological Weinberg score(Day 1 to Day 30)
- Evolution of pulmonary vascular permeability index(Between Day 1 and Day 7)
- Rate of withdraw or withhold life-sustaining treatments decision(Day 30)
- Evolution of FX06 concentration(Day 1)
- 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)
- Evolution of global end-diastolic volume index(Between Day 1 and Day 7)
- Overall survival(Day 30)
- Daily fluid balance(Between Day 1 and Day 7)
- Evolution of albuminemia(Between Day 1 and Day 7)
- Evolution of pulmonary Sequential Organ Failure Assessment) score.(Day 1 to day 15)
- 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)
- 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)