Multicenter, Open-label, Randomised Trial to Assess the Efficacy and Tolerability of Poractant Alfa(Porcine Surfactant, Curosurf®) in Hospitalized Patients With SARS-COV-19 Acute Respiratory Distress Syndrome (ARDS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 6
- 主要终点
- Number of Days Alive and Ventilator-free Days
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in hospitalized adult patients diagnosed with SARS-COV-19 acute respiratory distress syndrome (ARDS).
详细描述
This was a multicentre, open-label, randomized phase II proof-of-concept study.
The efficacy and safety of poractant alfa was evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients diagnosed with ARDS due to SARS-COV-19 infection.
Each patient randomized to the study treatment received 3 administrations of Curosurf ® with a 24 hours dosing interval. The assessment collection was up to Day 28, when the evaluation occurred at the Intensive Care Unit (ICU), or by phone call if the patient has already been discharged.
Seventy patients were planned to be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm). The control arm population received Standard of Care (SoC). This study was conducted in United Kingdom (UK), United States of America (US), and Italy.
Overall, 13 patients (Curosurf ® group) and 8 patients (control group) were randomised in the study. Due to low recruitment rate the study was terminated early for non-safety reasons.
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
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants were eligible to be included in the study if the following criteria apply:
- •Male or female ≥18 and ≤ 80 years of age
- •Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
- •Positive 2019-nCoV Reverse Transcription Polymerase Chain Reaction (rt-PCR) before randomisation
- •Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) ratio < 150 mmHg
- •Lung compliance ≤45 ml/cmH20
- •Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration
排除标准
- •Participants were excluded from the study if any of the following criteria apply:
- •Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
- •Weight < 40kg
- •Stage 4 severe chronic kidney disease (i.e., Estimated Glomerular Filtration Rate (eGFR) < 30)
- •Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration
- •Extracorporeal membrane oxygenation (ECMO)
研究组 & 干预措施
Poractant alfa
Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC)
干预措施: CUROSURF® (poractant alfa) (Drug)
结局指标
主要结局
Number of Days Alive and Ventilator-free Days
时间窗: up to 21 days
The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation. Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days.
次要结局
- Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Percentage of Patients Alive and Free of Respiratory Failure at Day 28(at Day 28)
- Number of Days Alive and Ventilator-Free at Day 28(at Day 28)
- Mortality at Day 21 and Day 28(at Day 21 and at Day 28)
- Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28(Day 21 and Day 28)
- Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28(Day 21 and Day 28)
- Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)(Day 28 or Discharge, whichever comes first)
- Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Length of ICU Stay (Days) at Day 28(up to 28 days)
- Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28(Day 28)
- Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28(Day 3 and Day 28 or discharge -- whichever comes first)
- Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)(at day 28 or discharge -- whichever comes first)
- Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28)
- Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2)(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2)(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3)(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Change From Baseline in Blood Parameter -- Lactate(up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28)
- Mortality -- TEAEs Leading to Death(up to day 28)