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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001654-21 | EudraCT Number |
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To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Molgramostim nebuliser solution | Experimental | 300μg molgramostim nebuliser solution |
|
| Placebo nebuliser solution | Placebo Comparator | Placebo nebuliser solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Molgramostim nebuliser solution | Drug | 300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mechanical ventilation | Need for mechanical ventilation within 15 days after randomization | During 15 days |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale): |
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susanne Herold, Prof. Dr. | Universitätsklinikum Giessen und Marburg (UKGM) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Carl Gustav Carus Dresden | Dresden | 01307 | Germany | |||
| Universitätsklinikum Essen |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20576718 | Background | Arndt CA, Koshkina NV, Inwards CY, Hawkins DS, Krailo MD, Villaluna D, Anderson PM, Goorin AM, Blakely ML, Bernstein M, Bell SA, Ray K, Grendahl DC, Marina N, Kleinerman ES. Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on disease-free survival and immunomodulation. a report from the Children's Oncology Group. Clin Cancer Res. 2010 Aug 1;16(15):4024-30. doi: 10.1158/1078-0432.CCR-10-0662. Epub 2010 Jun 24. | |
| 16474098 |
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Study protocol will be provided after publication
3 Months after publication
Central server
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| ID | Term |
|---|---|
| D045169 | Severe Acute Respiratory Syndrome |
| D011014 | Pneumonia |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
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| Placebo nebuliser solution | Other | Placebo nebulised seven times within 7 days via rapid nebuliser system |
|
| At day 15 and day 29 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 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 | At day 0 (day before first dose), day 1-9, and day 15 |
| Oxygen supply | Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98% | At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15 |
| Clinical parameter: temperature | Clinical parameter (4 times daily): temperature (°C degree) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 |
| Clinical parameter: blood pressure | Clinical parameter (4 times daily): blood pressure (mmHg) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 |
| Clinical parameter: heart beat | Clinical parameter (4 times daily): hear beat (beats per minute) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 |
| Clinical parameter: respiratory rate | Clinical parameter (4 times daily): respiratory rate (breaths per minute) | Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15 |
| Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) | Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage | Max. 48 hours before day 0 and at day 8-9 |
| Laboratory: C-reactive protein test | C-reactive protein test measures the amount of C-reactive protein in blood (mg/L) | At day 0, day 1-7, day 8-9 and day 15 |
| Laboratory: ferritin | Ferritin test measures the amount of ferritin in the blood (ng/ml) | At day 0, day 1-7, day 8-9 and day 15 |
| Laboratory: Interleukin-6 | Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml) | At day 0, day 1-7, day 8-9 and day 15 |
| Laboratory: procalcitonin | Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l) | At day 0, day 1-7, day 8-9 and day 15 |
| Bacterial pneumonia | Occurrence of secondary bacterial pneumonia | At day 0, day 1-7, day 8-9 and day 15 |
| Vaso-active drugs | Days on vaso-active drugs in a 29-day period | At day 29 |
| Mortality | All-cause mortality | At day 29 |
| GM-CSF | GM-CSF levels in serum | At day 0 and day 1-7 |
| Essen |
| 45147 |
| Germany |
| Krankenhaus Nordwest GmbH | Frankfurt am Main | 60488 | Germany |
| Universitätsklinikum Frankfurt | Frankfurt am Main | 60590 | Germany |
| Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen | Giessen | 35392 | Germany |
| Medizinische Hochschule Hannover | Hanover | 30625 | Germany |
| Universitätsklinikum Heidelberg | Heidelberg | 69126 | Germany |
| Lungenfachklinik Immenhausen | Immenhausen | 34376 | Germany |
| Sana Klinikum Offenbach | Offenbach | 63069 | Germany |
| Background |
| Ballinger MN, Paine R 3rd, Serezani CH, Aronoff DM, Choi ES, Standiford TJ, Toews GB, Moore BB. Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2006 Jun;34(6):766-74. doi: 10.1165/rcmb.2005-0246OC. Epub 2006 Feb 10. |
| 19590023 | Background | Cakarova L, Marsh LM, Wilhelm J, Mayer K, Grimminger F, Seeger W, Lohmeyer J, Herold S. Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair. Am J Respir Crit Care Med. 2009 Sep 15;180(6):521-32. doi: 10.1164/rccm.200812-1837OC. Epub 2009 Jul 9. |
| 32109013 | Background | Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28. |
| 18551128 | Background | Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008 Jul;8(7):533-44. doi: 10.1038/nri2356. |
| 24579839 | Background | Herold S, Hoegner K, Vadasz I, Gessler T, Wilhelm J, Mayer K, Morty RE, Walmrath HD, Seeger W, Lohmeyer J. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014 Mar 1;189(5):609-11. doi: 10.1164/rccm.201311-2041LE. No abstract available. |
| 21474645 | Background | Huang FF, Barnes PF, Feng Y, Donis R, Chroneos ZC, Idell S, Allen T, Perez DR, Whitsett JA, Dunussi-Joannopoulos K, Shams H. GM-CSF in the lung protects against lethal influenza infection. Am J Respir Crit Care Med. 2011 Jul 15;184(2):259-68. doi: 10.1164/rccm.201012-2036OC. Epub 2011 Apr 7. |
| 10021465 | Background | LeVine AM, Reed JA, Kurak KE, Cianciolo E, Whitsett JA. GM-CSF-deficient mice are susceptible to pulmonary group B streptococcal infection. J Clin Invest. 1999 Feb;103(4):563-9. doi: 10.1172/JCI5212. |
| 10667491 | Background | Matute-Bello G, Liles WC, Radella F 2nd, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome. Crit Care Med. 2000 Jan;28(1):1-7. doi: 10.1097/00003246-200001000-00001. |
| 24890235 | Background | Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED. Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose. Clin Drug Investig. 2014 Aug;34(8):553-64. doi: 10.1007/s40261-014-0208-z. |
| 12119223 | Background | Presneill JJ, Harris T, Stewart AG, Cade JF, Wilson JW. A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction. Am J Respir Crit Care Med. 2002 Jul 15;166(2):138-43. doi: 10.1164/rccm.2009005. |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
| D011024 | Pneumonia, Viral |