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

Phase 2

Completed

• Conditions: ARDS
• Interventions: Drug: inhaled molgramostim (rhGM-CSF); Drug: inhaled placebo

• Registration Number: NCT02595060
• Lead Sponsor: University of Giessen

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-01
• Study First Submitted QC: 2015-11-01
• Study First Posted: 2015-11-03
• Study Start: 2016-06-01
• Primary Completion: 2021-09-22
• Study Completion: 2022-07-31
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-30
• Last Update Posted: 2023-08-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
150 mcg inhaled molgramostim	inhaled molgramostim (rhGM-CSF)	once daily inhaled molgramostim (rhGM-CSF) for 3 days
450 mcg inhaled molgramostim	inhaled molgramostim (rhGM-CSF)	once daily inhaled molgramostim (rhGM-CSF) for 3 days
inhaled placebo	inhaled placebo	once daily inhaled placebo for 3 days

Primary Outcome Measures

Name	Time	Method
GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1)	baseline and Day 4/5	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.

Secondary Outcome Measures

Name	Time	Method
Oxygenation	Baseline to Day 11	PaO2/FiO2
Sequential Organ Failure Assessment (SOFA)	Baseline to Day 11
C-reactive Protein	Baseline to Day 11
Serum GM-CSF	Baseline, Days 1-4
Days on vasoactive drugs	Baseline to Day 28
Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions	baseline to 28 days
Acute Physiology and Chronic Health Evaluation (APACHE)	Baseline to Day 11
Extravascular Lung Water Index	Baseline to Day 11
All cause mortality	Baseline to Day 28

Trial Locations

Locations (7)

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie; 🇩🇪 Würzburg, Baden-Würtemberg, Germany

Universitätsklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie; 🇩🇪 Frankfurt, Germany

Universities of Marburg and Giessen Lung Center; 🇩🇪 Giessen, Germany

Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin; 🇩🇪 Jena, Germany

Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover, Klinik für Pneumologie; 🇩🇪 Hannover, Germany

University Hospital Marburg, Department of Anaesthesiology and Intensive Care Medicine; 🇩🇪 Marburg, Germany