Acute hypoxic respiratory failure of COVID-19 patients MedDRA version: 21.1 Level: LLT Classification code 10074615 Term: Hypoxic respiratory failure System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Leukine
Product Name: Leukine
Pharmaceutical Form: Powder for nebuliser solution
INN or Proposed INN: SARGRAMOSTIM
CAS Number: 123774-72-1
Concentration unit: µg microgram(s)
Concentration
Sponsors
University Hospital Ghent
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Recent (=2weeks prior to randomization) confident diagnosis of COVID-19 confirmed by antigen detection and/or PCR, and/or seroconversion or any other emerging and validated diagnostic test. - In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Patients with known history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony stimulating factor such as sargramostim, yeast-derived products, or any component of the product. - mechanical ventilation before start of study - patients with peripheral white blood cell count above 25.000 per microliter and/or active myeloid malignancy -patients on high dose systemic steroids (> 20 mg methylprednisolone or equivalent) -patients on lithium carbonate therapy - Patients enrolled in another investigational drug study - Pregnant or breastfeeding females (all female subjects regardless of childbearing potential status must have negative pregnancy test at screening) - Patients with serum ferritin >2000 mcg/ml (which will exclude ongoing HLH)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate whether the administration of inhaled sargramostim (Leukine®) at a dose of 250 mcg daily during 5 days improves oxygenation in COVID-19 patients with acute hypoxic respiratory failure .;Secondary Objective: - to study if early intervention with sargramostim is safe (number of AEs/SAEs) - to study if early intervention with inhaled sargramostim affects clinical outcome defined by duration of hospital stay, 6-point ordinal scale, clinical sign score, SOFA score, NEWS2 score - to study if early intervention with sargramostim affects the rate of nosocomial infection - to study if early intervention with inhaled sargramostim affects progression to mechanical ventilation and/or ARDS - to study if treatment with sargramostim affects all-cause mortality rate at 4 and 20 weeks post inclusion -to study if treatment with sargramostim affects features of secondary haemophagocytic lymphohistiocytosis, defined by HS score - to study if treatment with sargramostim has a favourable effect on long term 10-20 week follow up ;Primary end point(s): To measure the effectiveness of sargramostim on restoring lung homeostasis, the primary endpoint of this intervention is measuring oxygenation after 5 DAYS of inhaled (and intravenous) treatment through assessment of pretreatment (day 0) and post-treatment (day 5) ratio of PaO2/FiO2 and through measurement of the P(A-a)O2 gradient, which can easily be performed in the setting of clinical observation of patients admitted to the COVID -19 ward or ICU COVID-19 unit. Preferentially, this measurement should be done in the upright position, while breathing room air for a minimum of 3 minutes.. If this is impossible due to need for supplemental oxygen, FiO2 and oxygen supplementation method should be recorded in patient record, so that A-a gradient can be normalized for age expected normal A-a gradient while on supplemental oxygen use. During the 5 day treatment period, we will perform daily m | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - to study if early intervention with sargramostim is safe (number of AEs/SAEs) Although sargramostim has been given previously by inhalation to patients with ARDS and interstitial lung disease, data on safety in patients with COVID-19 infection are currently lacking. Since we are randomizing against 5 days of no sargramostim treatment, comparison of AEs and SAEs between group A and group B will be very informative. -to study if early intervention with inhaled sargramostim affects clinical outcome defined by length of hospital stay mean change in 6-point ordinal scale change between day 1, day 6 and - to study if early intervention with sargramostim affects the rate of nosocomial infection Patients with viral respiratory infection are at risk of secondary bacterial infections. As part of routine clinical care, sputum samples will be collected in patients suspected of secondary bacterial pneumonia, and checked for the presence of bacteria. -to study if early intervention with inhaled sargramostim affects progression to mechanical ventilation and/or ARDS Decreasing oxygenation often leads to the need for non-invasive or invasive mechanical ventilation, and if severe enough to a diagnosis of ARDS. We will therefore as a secondary endpoint also study if early intervention with inhaled sargramostim prevents progression to criteria-defined ARDS (according to the American-European Consensus Conference (AECC) diagnostic criteria for ARDS: acute onset; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) of 200 or less, regardless of positive end-expiratory pressure; bilateral infiltrates seen on frontal chest radiograph; and pulmonary artery wedge pressure of 18 mm Hg or less when measured, or no clinical evidence of left atrial hypertension), requiring high-flow oxygen devices, non-invasive mechanical ventilation, mechanical ventilation, by measuring the day from admission when this diagnosis is made o | — |
Countries
Belgium
Contacts
Public ContactHIRUZ CTU
University Hospital Ghent
Outcome results
None listed