acute respiratory distress sydnrome (ARDS) secondary to Covid-19 MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Prolastin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: HUMAN ALPHA1-PROTEINASE INHIBITOR
CAS Number: 9041-92-3
Other descriptive name: HUMAN ALPHA
Sponsors
Royal College of Surgeons Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Laboratory confirmed diagnosis of COVID-19 infection 2. Moderate to severe ARDS with a PaO2/FiO2 ratio 18 years of age 4. Patients receiving invasive mechanical ventilation or non-invasive ventilation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: 1. Not receiving invasive mechanical ventilation or non invasive ventilation 2. More than 96 hours from the onset of ARDS 3. Age 12 13. DNAR (Do Not Attempt Resuscitation) order in place 14. Treatment withdrawal imminent within 24 hours 15. Prisoners 16. Non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available. 17. Enrolled in a concomitant clinical trial of interferon therapies, immune plasma therapies or immunoglobulin. 18. IgA deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is to conduct a clinical trial of IV AAT as a prospective anti-inflammatory therapy for severely ill COVID-19 patients with ARDS requiring ICU admission. The primary objective is to demonstrate a biological effect of IV Prolastin administered weekly at 120mg per kilogram of body weight in patients with severe COVID-19 illness requiring intubation and mechanical ventilation for ARDS by reducing circulating levels of IL-6 as measured by plasma ELISA. The study sample size is sufficient to demonstrate a significant difference in patients receiving Prolastin versus patients receiving placebo.;Secondary Objective: determine the safety and tolerability of [IV Prolastin administered once at 120mg/kg of body weight] and [IV Prolastin administered weekly at 120mg/kg of body weight for 4 weeks], as assessed by the number of AEs and SAEs and determine the effects of [IV Prolastin administered once at 120mg per kilogram of body weight] and [IV Prolastin administered weekly at 120mg per kilogram of body weight for 4 weeks] on: Physiological indices of respiratory dysfunction reflecting severity of ARDS, as measured by oxygenation index (OI), respiratory compliance Sequential organ failure assessment (SOFA) score Mortality Time on ventilator in days Circulating alpha-1 antitrypsin (AAT) levels Circulating levels of IL-1ß, IL-8, IL-10, soluble TNF receptor 1 Development of shock Acute kidney injury Need for renal replacement therapy Clinical relapse Length of ICU stay in days;Primary end point(s): The primary effectiveness outcome measure, a continuous variable, is IL-6 in plasma as measured by ELISA.;Timepoint(s) of evaluation of this end point: day 2 , day 7, day 14, day 21 and day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and tolerability of IMP in the respective groups, as defined by the number of SEAs and AEs, binary variable • PaO2/FiO2 ratio, continuous variable • Respiratory compliance, continuous variable • Sequential organ failure assessment (SOFA) score, continuous variable • Mortality, binary variable • Time on ventilator in days, continuous variable • Circulating AAT levels as measured by nephelometry, continuous variable • Plasma levels of IL-1ß as measured by ELISA, continuous variable • Plasma levels of IL-8 as measured by ELISA, continuous variable • Plasma levels of IL-10 as measured by ELISA, continuous variable • Plasma levels levels of soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-a) as measured by ELISA, continuous variable • Development of shock, defined for the purpose of this study as life-threatening organ dysfunction caused by a dysregulated response to infection, with critical reduction in tissue perfusion and acute failure of multiple organs, including the lungs, kidneys, and liver, binary variable • Acute kidney injury defined as an abrupt sustained rise in urea and creatinine, binary variable • Need for renal replacement therapy, binary variable • Clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement, binary variable • Secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture, binary variable ;Timepoint(s) of evaluation of this end point: day 2 , day 7, day 14, day 21 and day 28 | — |
Countries
Ireland
Contacts
Public ContactMandy Jackson
Royal College of Surgeons Ireland
Outcome results
None listed