GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia

Phase 2

Completed

• Conditions: COVID-19 Pneumonia; Severe Acute Respiratory Syndrome (SARS) Pneumonia
• Interventions: Drug: Molgramostim nebuliser solution; Other: Placebo nebuliser solution

• Registration Number: NCT04569877
• Lead Sponsor: University of Giessen

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.

Study Timeline

• Study Start: 2020-09-24
• Study First Submitted: 2020-09-25
• Study First Submitted QC: 2020-09-29
• Study First Posted: 2020-09-30
• Status Verified: 2022-06
• Primary Completion: 2022-06-21
• Study Completion: 2022-09-20
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Molgramostim nebuliser solution	Molgramostim nebuliser solution	300μg molgramostim nebuliser solution
Placebo nebuliser solution	Placebo nebuliser solution	Placebo nebuliser solution

Primary Outcome Measures

Name	Time	Method
Mechanical ventilation	During 15 days	Need for mechanical ventilation within 15 days after randomization

Secondary Outcome Measures

Name	Time	Method
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 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: 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: 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)
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)
Mortality	At day 29	All-cause mortality
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%
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: 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
GM-CSF	At day 0 and day 1-7	GM-CSF levels in serum
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.
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)
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)

Trial Locations

Locations (9)

Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen; 🇩🇪 Gießen, Germany

Universitätsklinikum Essen; 🇩🇪 Essen, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt am Main, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitätsklinikum Carl Gustav Carus Dresden; 🇩🇪 Dresden, Germany

Krankenhaus Nordwest GmbH; 🇩🇪 Frankfurt am Main, Germany

Sana Klinikum Offenbach; 🇩🇪 Offenbach am Main, Germany

Lungenfachklinik Immenhausen; 🇩🇪 Immenhausen, Germany