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

Summary

To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.

Timeline

Start

2020-09-24

Primary completion

2022-06-21

Completion

2022-09-20

Publications

• 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.
• 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.
• 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.
• 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.
• Background Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008 Jul;8(7):533-44. doi: 10.1038/nri2356.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications