Clinical trial NCT04502433: Poractant Alfa (Curosurf®)) -- Effect in Adult Patients Diagnosed With 2019 Novel Coronavirus (SARS-COV-19; (Covid-19)) Acute Respiratory Distress Syndrome (ARDS)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Keywords: acute respiratory distress syndrome
ARDS
Adults
Surfactant
Poractant alfa (porcine surfactant, Curosurf®),
Curosurf®
Coronavirus disease (COVID-19)
Coronavirus 2019 Disease
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Seventy patients will 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).
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Curosurf® is a pulmonary surfactant of natural origin which, when delivered endotracheally (ET). Curosurf® is currently approved for marketing as treatment of premature neonates with RDS or at risk of Respiratory Distress Syndrome (RDS). Chiesi Farmaceutici S.p.A (Chiesi) conducted this study with its porcine-derived surfactant, Curosurf® (poractant alfa), to evaluate the efficacy and safety in ventilated adult patients who were critically unwell in intensive care with SARS-COV-19 ARDS.

Eligibility criteria: Inclusion Criteria:

Participants were eligible to be included in the study if the following criteria apply:

1. Male or female ≥18 and ≤ 80 years of age
2. Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure)
3. Positive 2019-nCoV Reverse Transcription Polymerase Chain Reaction (rt-PCR) before randomisation
4. Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) ratio \< 150 mmHg
5. Lung compliance ≤45 ml/cmH20
6. Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration

Exclusion Criteria:

Participants were excluded from the study if any of the following criteria apply:

1. Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax)
2. Weight \< 40kg
3. Stage 4 severe chronic kidney disease (i.e., Estimated Glomerular Filtration Rate (eGFR) \< 30)
4. Pregnancy
5. Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration
6. Extracorporeal membrane oxygenation (ECMO)

Primary outcomes:
measure: Number of Days Alive and Ventilator-free Days
timeFrame: up to 21 days
Secondary outcomes:
measure: Percentage of Patients Alive and Free of Respiratory Failure at Day 28
timeFrame: at Day 28
measure: Number of Days Alive and Ventilator-Free at Day 28
timeFrame: at Day 28
measure: Mortality at Day 21 and Day 28
timeFrame: at Day 21 and at Day 28
measure: Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28
timeFrame: Day 21 and Day 28
measure: Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28
timeFrame: Day 21 and Day 28
measure: Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)
timeFrame: Day 28 or Discharge, whichever comes first
measure: Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: Length of ICU Stay (Days) at Day 28
timeFrame: up to 28 days
measure: Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28
timeFrame: Day 28
measure: Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28
timeFrame: Day 3 and Day 28 or discharge -- whichever comes first
measure: Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)
timeFrame: at day 28 or discharge -- whichever comes first
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: 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
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
measure: Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2)
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2)
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3)
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Change From Baseline in Blood Parameter -- Lactate
timeFrame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
measure: Mortality -- TEAEs Leading to Death
timeFrame: up to day 28
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Bologna
country: Italy
facility: Chiesi site # 14
city: Modena
country: Italy
facility: Chiesi site #13
city: London
country: United Kingdom
facility: UCLH and UCL 250 Euston Road
city: London
country: United Kingdom
facility: Chiesi site #4
city: Southampton
country: United Kingdom
facility: Chiesi site # 12
Study officials:
affiliation: University College, London
name: Clark Howard, Prof. /MD
role: PRINCIPAL_INVESTIGATOR
References: