ARDS
Conditions
Keywords
acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration
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.
Interventions
DRUGinhaled molgramostim (rhGM-CSF)
DRUGinhaled placebo
formulated as the active substance without molgramostim
Sponsors
University of Giessen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Oxygenation | Baseline to Day 11 | PaO2/FiO2 |
| Acute Physiology and Chronic Health Evaluation (APACHE) | Baseline to Day 11 | — |
| Sequential Organ Failure Assessment (SOFA) | Baseline to Day 11 | — |
| Extravascular Lung Water Index | Baseline to Day 11 | — |
| Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions | baseline to 28 days | — |
| Days on vasoactive drugs | Baseline to Day 28 | — |
| All cause mortality | Baseline to Day 28 | — |
| Serum GM-CSF | Baseline, Days 1-4 | — |
| C-reactive Protein | Baseline to Day 11 | — |
Countries
Germany
Outcome results
None listed