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

NCT ID: NCT04569877

Last Updated: 2023-05-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-24

Study Completion Date

2022-09-20

Brief Summary

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

Detailed Description

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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.

Conditions

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Severe Acute Respiratory Syndrome (SARS) Pneumonia COVID-19 Pneumonia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Molgramostim nebuliser solution

300μg molgramostim nebuliser solution

Group Type EXPERIMENTAL

Molgramostim nebuliser solution

Intervention Type DRUG

300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system

Placebo nebuliser solution

Placebo nebuliser solution

Group Type PLACEBO_COMPARATOR

Placebo nebuliser solution

Intervention Type OTHER

Placebo nebulised seven times within 7 days via rapid nebuliser system

Interventions

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Molgramostim nebuliser solution

300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system

Intervention Type DRUG

Placebo nebuliser solution

Placebo nebulised seven times within 7 days via rapid nebuliser system

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Giessen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanne Herold, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Giessen und Marburg (UKGM)

Locations

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Universitätsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Krankenhaus Nordwest GmbH

Frankfurt am Main, , Germany

Site Status

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Site Status

Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen

Giessen, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Site Status

Sana Klinikum Offenbach

Offenbach, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 20576718 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16474098 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19590023 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32109013 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 18551128 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24579839 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21474645 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10021465 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10667491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24890235 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12119223 (View on PubMed)

Other Identifiers

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2020-001654-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KKS-279

Identifier Type: -

Identifier Source: org_study_id

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