Efficacy and Safety of Dornase Alfa Aerosol in ARDS Secondary to SARS-CoV-2 Coronavirus Respiratory Infection - COVID-19
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Efficacy of intratracheal administration: occurrence of at least one grade improvement
研究概览
简要总结
This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs.
The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial.
The goal is to recruit 100 patients.
详细描述
Acute Respiratory Distress Syndrome (ARDS) is the most severe form of COVID-19 with a mortality reaching 50%. To date, no specific therapy has been shown to be effective. During an acute viral respiratory infection, lungs are the site of an intense neutrophil recruitment. Recruited neutrophils generate NETs (extracellular neutrophil traps) in the alveoli and bronchioles. NETs have been shown to be involved in bronchoalveolar congestion and amplification of the inflammatory response during viral pneumonia responsible for ARDS. Deoxyribonuclease 1 (DNAse 1) is an enzyme capable of cutting apart extracellular DNA strands, the backbone of NETs. The administration of recombinant human DNAse 1 (dornase alfa) leads to the loosening of the broncho-alveolar mucus and to a reduction in the inflammatory response within the alveoli.
By conducting a randomized, open-label, multicenter, controlled trial, our goal is to evaluate the efficacy and safety of aerosolized intra-tracheal dornase alfa administration in mechanically ventilated patients hospitalized for COVID19-related ARDS.
This is a randomized, controlled, multicentric, open-label clinical trial to evaluate the efficacy and safety of dornase alfa administration aerosol, intensive care hospitalized patients with COVID19-related ARDS.
The comparison of D7-D0 between the groups will be carried out using a linear regression fitted to the stratification factors.
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
- Single (Participant)
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
- 未提供
排除标准
- •Known hypersensitivity to Dornase alfa or any of the excipients;
- •Pregnant or breastfeeding status;
- •Patient with legal protection.
研究组 & 干预措施
Experimental group
Dornase alfa will be administered by nebulization, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer. The remainder of the management will be performed in accordance with good practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure checking every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2<150, early enteral nutrition, glycemic control, a sedation protocol based on the RASS score.
干预措施: Dornase Alfa Inhalation Solution [Pulmozyme] (Drug)
Control group
Patients will receive the usual care in accordance with good practice.
干预措施: standard procedure (Procedure)
结局指标
主要结局
Efficacy of intratracheal administration: occurrence of at least one grade improvement
时间窗: Day 7
The primary endpoint is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from severe to moderate or from moderate to mild
次要结局
未报告次要终点