ARDSPhase 2GI-HOPENCT02595060
Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Inhalation to Improve Host Defense and Pulmonary Barrier Restoration
A Phase 2 study testing inhaled molgramostim (rhGM-CSF) in people with ARDS, run by University of Giessen at 7 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ARDS
- What is being tested?
- inhaled molgramostim (rhGM-CSF)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 7 sitesGermany
- Study dates
- 1 Jun 2016to 31 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent form by the patient or a legal representative according to local regulations
- Man or woman 18 to 75 years of age, inclusive
- 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.
- 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.
- Diagnosis of ARDS according to the Berlin ARDS definition.
- 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
Who cannot join
- Receiving vasopressors of >100 µg/min
- History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer
- Malignancy with expected survival time of less than 6 months
- History of or listing for lung transplantation
- Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug
- Any anti-malignant chemotherapy within 24 hours prior to first dose of study drug
Show all 11Show fewer
- AIDS or known history of HIV infection
- Pregnancy
- Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells
- History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine™, Topleucon™)
- Participation in another clinical trial within 90 days prior to the first dose of study drug
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Germany7 sites
Universitätsklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
Frankfurt, 60590
Universities of Marburg and Giessen Lung Center
Giessen
Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin
Hamburg, 20246
Medizinische Hochschule Hannover, Klinik für Pneumologie
Hanover, 30625
Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin
Jena, 07747
University Hospital Marburg, Department of Anaesthesiology and Intensive Care Medicine
Marburg
Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie
Würzburg, Baden-Würtemberg, 97080
About this study
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
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.
- Conditions
- ARDS
- Being tested
- inhaled molgramostim (rhGM-CSF), inhaled placebo
- Keywords
- acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration
- Medical subject headings
- Acute Lung Injury, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled molgramostim (rhGM-CSF)Drug
inhaled placeboDrug
formulated as the active substance without molgramostim
| Study group | Role | What they receive |
|---|---|---|
| 150 mcg inhaled molgramostim | Experimental | once daily inhaled molgramostim (rhGM-CSF) for 3 days Receives: Drug: inhaled molgramostim (rhGM-CSF) |
| 450 mcg inhaled molgramostim | Experimental | once daily inhaled molgramostim (rhGM-CSF) for 3 days Receives: Drug: inhaled molgramostim (rhGM-CSF) |
| inhaled placebo | Placebo comparator | once daily inhaled placebo for 3 days Receives: Drug: inhaled placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline and Day 4/5
Secondary outcomes (9)
Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions
Measured: baseline to 28 days
Oxygenation
PaO2/FiO2
Measured: Baseline to Day 11
Acute Physiology and Chronic Health Evaluation (APACHE)
Measured: Baseline to Day 11
Sequential Organ Failure Assessment (SOFA)
Measured: Baseline to Day 11
Extravascular Lung Water Index
Measured: Baseline to Day 11
C-reactive Protein
Measured: Baseline to Day 11
Days on vasoactive drugs
Measured: Baseline to Day 28
All cause mortality
Measured: Baseline to Day 28
Serum GM-CSF
Measured: Baseline, Days 1-4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study start1 Jun 2016
- Primary completion22 Sep 2021
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for ARDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Giessen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susanne Herold, Prof.Dr.med.,PhD, Principal investigator, Universities of Giessen and Marburg Lung Centers, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595060
- Sponsor's protocol ID
- MOL-ARDS-002
- Acronym
- GI-HOPE
- Status last verified
- Aug 2023
- First submitted
- 1 Nov 2015
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24579839Cakarova 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.
PubMed 19590023Unkel 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.
PubMed 22996662Ballinger 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.
PubMed 16474098Standiford 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.
PubMed 22160309
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02595060
- Acronym / sponsor ID
- GI-HOPE / MOL-ARDS-002
- Conditions
- ARDS
- Keywords
- acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of GiessenUniversity, hospital or other
- Study start
- 1 Jun 2016 (actual)
- Primary completion
- 22 Sep 2021 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 150 mcg inhaled molgramostim | Experimental | Drug: inhaled molgramostim (rhGM-CSF)once daily inhaled molgramostim (rhGM-CSF) for 3 days |
| 450 mcg inhaled molgramostim | Experimental | Drug: inhaled molgramostim (rhGM-CSF)once daily inhaled molgramostim (rhGM-CSF) for 3 days |
| inhaled placebo | Placebo comparator | Drug: inhaled placeboonce daily inhaled placebo for 3 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Signed informed consent form by the patient or a legal representative according to local regulations
- Man or woman 18 to 75 years of age, inclusive
- 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.
- 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.
- Diagnosis of ARDS according to the Berlin ARDS definition.
Key exclusion criteria (11 listed)
- Receiving vasopressors of >100 µg/min
- History of liver cirrhosis Child Pugh C, chronic hemodialysis (before severe pneumonia/ARDS), lung cancer
- Malignancy with expected survival time of less than 6 months
- History of or listing for lung transplantation
- Highly immunosuppressive therapy or anti-malignant combination chemotherapy within 3 weeks prior to first dose of study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inhaled molgramostim (rhGM-CSF) | Drug | 150 mcg inhaled molgramostim, 450 mcg inhaled molgramostim |
| inhaled placeboformulated as the active substance without molgramostim | Drug | inhaled placebo |
Primary outcome
GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1)
Time frame: 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.
9 secondary outcomes
Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions
Time frame: baseline to 28 days
Oxygenation
Time frame: Baseline to Day 11
Acute Physiology and Chronic Health Evaluation (APACHE)
Time frame: Baseline to Day 11
Sequential Organ Failure Assessment (SOFA)
Time frame: Baseline to Day 11
Extravascular Lung Water Index
Time frame: Baseline to Day 11
C-reactive Protein
Time frame: Baseline to Day 11
Days on vasoactive drugs
Time frame: Baseline to Day 28
All cause mortality
Time frame: Baseline to Day 28
Serum GM-CSF
Time frame: Baseline, Days 1-4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- Background: PubMed 24579839Herold 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: PubMed 19590023Cakarova 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: PubMed 22996662Unkel 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.
- Background: PubMed 16474098Ballinger 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: PubMed 22160309Standiford 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanne Herold, Prof.Dr.med.,PhD principal investigator
Universities of Giessen and Marburg Lung Centers, Germany
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inhaled molgramostim (rhGM-CSF) in people with ARDS, run by University of Giessen at 7 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1) (time frame: baseline and Day 4/5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02595060, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.