Clinical trial NCT04569877: GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia
Official title: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Acute Respiratory Syndrome (SARS) Pneumonia
COVID-19 Pneumonia
Keywords: GM-CSF
COVID-19
ARDS
Lead sponsor: University of Giessen
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mechanical ventilation
timeFrame: During 15 days
Secondary outcomes:
measure: Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale):
timeFrame: At day 15 and day 29
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: At day 0 (day before first dose), day 1-9, and day 15
measure: Oxygen supply
timeFrame: At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15
measure: Clinical parameter: temperature
timeFrame: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
measure: Clinical parameter: blood pressure
timeFrame: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
measure: Clinical parameter: heart beat
timeFrame: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
measure: Clinical parameter: respiratory rate
timeFrame: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
measure: Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)
timeFrame: Max. 48 hours before day 0 and at day 8-9
measure: Laboratory: C-reactive protein test
timeFrame: At day 0, day 1-7, day 8-9 and day 15
measure: Laboratory: ferritin
timeFrame: At day 0, day 1-7, day 8-9 and day 15
measure: Laboratory: Interleukin-6
timeFrame: At day 0, day 1-7, day 8-9 and day 15
measure: Laboratory: procalcitonin
timeFrame: At day 0, day 1-7, day 8-9 and day 15
measure: Bacterial pneumonia
timeFrame: At day 0, day 1-7, day 8-9 and day 15
measure: Vaso-active drugs
timeFrame: At day 29
measure: Mortality
timeFrame: At day 29
measure: GM-CSF
timeFrame: At day 0 and day 1-7
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Gießen
country: Germany
facility: Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Offenbach am Main
country: Germany
facility: Sana Klinikum Offenbach
Study officials:
affiliation: Universitätsklinikum Giessen und Marburg (UKGM)
name: Susanne Herold, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
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