COVID-19 Pneumonia, Severe Acute Respiratory Syndrome (SARS) Pneumonia
Conditions
Keywords
GM-CSF, COVID-19, ARDS
Brief summary
To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.
Detailed description
COVID-19 pneumonia is induced by the newly emerging pandemic Severe acute respiratory Syndrome (SARS) coronavirus 2 and results in progression to the acute respiratory distress syndrome (ARDS). Apart from protective ventilation, fluid restriction, prone positioning and extracorporeal membrane oxygenation (ECMO), no specific therapeutic options exist to treat this devastating disease with a mortality rate of up to 50%. The growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) is widely recognized to promote differentiation and mobilization of different myeloid leukocyte subsets including neutrophils, tissue macrophages/dendritic cells or their circulating precursors. GM-CSF was found to be crucial for alveolar epithelial repair following hyperoxic and inflammatory lung injury.The aim of the current trial is to prevent progression to ARDS in COVID-19 pneumonia patients by preemptive GM-CSF Inhalation.
Interventions
DRUGMolgramostim nebuliser solution
300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system
Placebo nebulised seven times within 7 days via rapid nebuliser system
Sponsors
University of Giessen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent form by the patient according to local regulations 2. Man or non-pregnant woman 3. Age ≥18 years 4. Willingness of patients with reproductive potential to use highly effective contraceptive methods by practicing abstinence or by using at least two methods of birth control from the date of consent to the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used \*. 5. Lab-confirmed COVID-19 pneumonia where pneumonia is diagnosed by radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR clinical assessment (evidence of rales/crackles on exam) AND pulse oximeter oxygen saturation ≤ 94% at room air in patients that do not have chronic hypoxia; or less than their baseline oxygenation in patients that suffer from chronic hypoxia 6. Negative serum pregnancy test in women of childbearing potentia
Exclusion criteria
1. Pregnancy or breast feeding 2. Autoimmune thrombocytopenia, myelodysplastic syndromes with \> 20% marrow blast cells 3. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®) 4. Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient 5. Simultaneous participation in another clinical trial with an experimental treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mechanical ventilation | During 15 days | Need for mechanical ventilation within 15 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | At day 0 (day before first dose), day 1-9, and day 15 | Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] will be measured at day 0 (day before first dose), day 1-9, and day 15 |
| Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale): | At day 15 and day 29 | 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death. |
| Oxygen supply | At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15 | Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98% |
| Clinical parameter: temperature | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | Clinical parameter (4 times daily): temperature (°C degree) |
| Clinical parameter: blood pressure | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | Clinical parameter (4 times daily): blood pressure (mmHg) |
| Clinical parameter: heart beat | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | Clinical parameter (4 times daily): hear beat (beats per minute) |
| Clinical parameter: respiratory rate | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 | Clinical parameter (4 times daily): respiratory rate (breaths per minute) |
| Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) | Max. 48 hours before day 0 and at day 8-9 | Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage |
| Laboratory: C-reactive protein test | At day 0, day 1-7, day 8-9 and day 15 | C-reactive protein test measures the amount of C-reactive protein in blood (mg/L) |
| Laboratory: ferritin | At day 0, day 1-7, day 8-9 and day 15 | Ferritin test measures the amount of ferritin in the blood (ng/ml) |
| Laboratory: Interleukin-6 | At day 0, day 1-7, day 8-9 and day 15 | Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml) |
| Laboratory: procalcitonin | At day 0, day 1-7, day 8-9 and day 15 | Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l) |
| Bacterial pneumonia | At day 0, day 1-7, day 8-9 and day 15 | Occurrence of secondary bacterial pneumonia |
| Vaso-active drugs | At day 29 | Days on vaso-active drugs in a 29-day period |
| Mortality | At day 29 | All-cause mortality |
| GM-CSF | At day 0 and day 1-7 | GM-CSF levels in serum |
Countries
Germany
Outcome results
None listed