Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Inhalation to Improve Host Defense and Pulmonary Barrier Restoration

ARDS Clinical Trial

— GI-HOPE  

Official title:

GM-CSF Inhalation to Improve Host Defense and Pulmonary Barrier Restoration (GI-HOPE). A Randomized, Double-blind, Parallel Group, Multicenter, Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02595060
• Other study ID #: MOL-ARDS-002
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2016
• Est. completion date: July 31, 2022

Study information

• Verified date: August 2023
• Source: University of Giessen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial evaluates efficacy and safety of inhaled molgramostim (rhGM-CSF) in 45 patients with pneumonia associated acute respiratory distress syndrome (ARDS). A third of the patients will receive 150 mcg inhaled molgramostim, another third 450 mcg and the remaining third will receive inhaled placebo for 3 days. The patients will be followed for 28 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 31, 2022
• Est. primary completion date: September 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form by the patient or a legal representative according to local regulations

2. Man or woman 18 to 75 years of age, inclusive

3. Women who have been post-menopausal for more than 1 year or women of childbearing potential period using a highly efficient method of contraception (i.e. a method with less than 1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tube occlusion, vasectomized partner, sexual abstinence) during dosing and hospitalisation. Women must have a negative serum or urine pregnancy test before the first dose of study medication and must not be lactating.

4. Diagnosis of pneumonia-associated ARDS, where the underlying condition is Community-Acquired Pneumonia (CAP) or Hospital-Acquired Pneumonia (HAP) in patients not on invasive ventilation upon diagnosis of HAP.

5. Diagnosis of ARDS according to the Berlin ARDS definition.

6. Requirement for positive pressure ventilation (non-invasive or via endotracheal tube) for more than 72 hours in total with inspiratory oxygen concentration (FiO2) = 50% (or less when on additional ECMO therapy) not longer than 14 days

Exclusion Criteria:

1. Receiving vasopressors of >100 µg/min

2. History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer

3. Malignancy with expected survival time of less than 6 months

4. History of or listing for lung transplantation

5. Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug

6. Any anti-malignant chemotherapy within 24 hours prior to first dose of study drug

7. AIDS or known history of HIV infection

8. Pregnancy

9. Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells

10. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine™, Topleucon™)

11. Participation in another clinical trial within 90 days prior to the first dose of study drug

Related Conditions & MeSH terms

• ARDS
• Respiratory Aspiration

Intervention

Drug:
• inhaled molgramostim (rhGM-CSF)

• inhaled placebo
formulated as the active substance without molgramostim

Locations

Country	Name	City	State
Germany	Universitätsklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie	Frankfurt
Germany	Universities of Marburg and Giessen Lung Center	Giessen
Germany	Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Pneumologie	Hannover
Germany	Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin	Jena
Germany	University Hospital Marburg, Department of Anaesthesiology and Intensive Care Medicine	Marburg
Germany	Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie	Würzburg	Baden-Würtemberg

Sponsors (1)

Lead Sponsor	Collaborator
University of Giessen

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

Standiford LR, Standiford TJ, Newstead MJ, Zeng X, Ballinger MN, Kovach MA, Reka AK, Bhan U. TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol. 2012 Mar 1;302(5):L447-54. doi: 10.1152/ajplung.00415.2010. Epub 2011 Dec 9. — View Citation

Unkel B, Hoegner K, Clausen BE, Lewe-Schlosser P, Bodner J, Gattenloehner S, Janssen H, Seeger W, Lohmeyer J, Herold S. Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest. 2012 Oct;122(10):3652-64. doi: 10.1172/JCI62139. Epub 2012 Sep 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1)	The GI-HOPE score assesses change in bronchoalveolar lavage fluid (BALF) mononuclear phagocyte activation/polarization by flow cytometry (mean fluorescence intensities of parameters CD80, CD86, CD206, HLA-DR) with respect to baseline.	baseline and Day 4/5
Secondary	Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions		baseline to 28 days
Secondary	Oxygenation	PaO2/FiO2	Baseline to Day 11
Secondary	Acute Physiology and Chronic Health Evaluation (APACHE)		Baseline to Day 11
Secondary	Sequential Organ Failure Assessment (SOFA)		Baseline to Day 11
Secondary	Extravascular Lung Water Index		Baseline to Day 11
Secondary	C-reactive Protein		Baseline to Day 11
Secondary	Days on vasoactive drugs		Baseline to Day 28
Secondary	All cause mortality		Baseline to Day 28
Secondary	Serum GM-CSF		Baseline, Days 1-4