Back to results

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

Primary Purpose

ARDS

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

inhaled molgramostim (rhGM-CSF)

inhaled placebo

About this trial

This is an interventional treatment trial for ARDS focused on measuring acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

150 mcg inhaled molgramostim

450 mcg inhaled molgramostim

inhaled placebo

Arm Description

once daily inhaled molgramostim (rhGM-CSF) for 3 days

once daily inhaled placebo for 3 days

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions

Oxygenation

PaO2/FiO2

Acute Physiology and Chronic Health Evaluation (APACHE)

Sequential Organ Failure Assessment (SOFA)

Extravascular Lung Water Index

C-reactive Protein

Days on vasoactive drugs

All cause mortality

Serum GM-CSF

Full Information

NCT ID

NCT02595060

First Posted

November 1, 2015

Last Updated

August 30, 2023

Sponsor

University of Giessen

1. Study Identification

Unique Protocol Identification Number

NCT02595060

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

June 1, 2016 (Actual)

Primary Completion Date

September 22, 2021 (Actual)

Study Completion Date

July 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Giessen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

ARDS

Keywords

acute lung injury, molgramostim, GM-CSF, pneumonia, barrier restoration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

150 mcg inhaled molgramostim

Arm Type

Experimental

Arm Description

once daily inhaled molgramostim (rhGM-CSF) for 3 days

Arm Title

450 mcg inhaled molgramostim

Arm Type

Experimental

Arm Description

once daily inhaled molgramostim (rhGM-CSF) for 3 days

Arm Title

inhaled placebo

Arm Type

Placebo Comparator

Arm Description

once daily inhaled placebo for 3 days

Intervention Type

Drug

Intervention Name(s)

inhaled molgramostim (rhGM-CSF)

Intervention Type

Drug

Intervention Name(s)

inhaled placebo

Intervention Description

formulated as the active substance without molgramostim

Primary Outcome Measure Information:

Title

GI-HOPE score representing changes at Day 4/5 with respect to Baseline (Day -1)

Description

Time Frame

baseline and Day 4/5

Secondary Outcome Measure Information:

Title

Number of patients with Adverse Events (AE), Serious AEs and Adverse Drug Reactions

Time Frame

baseline to 28 days

Title

Oxygenation

Description

PaO2/FiO2

Time Frame

Baseline to Day 11

Title

Acute Physiology and Chronic Health Evaluation (APACHE)

Time Frame

Baseline to Day 11

Title

Sequential Organ Failure Assessment (SOFA)

Time Frame

Baseline to Day 11

Title

Extravascular Lung Water Index

Time Frame

Baseline to Day 11

Title

C-reactive Protein

Time Frame

Baseline to Day 11

Title

Days on vasoactive drugs

Time Frame

Baseline to Day 28

Title

All cause mortality

Time Frame

Baseline to Day 28

Title

Serum GM-CSF

Time Frame

Baseline, Days 1-4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susanne Herold, Prof.Dr.med.,PhD

Organizational Affiliation

Universities of Giessen and Marburg Lung Centers, Germany

Official's Role

Principal Investigator

Facility Information:

Facility Name

Klinik und Poliklinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie

City

Würzburg

State/Province

Baden-Würtemberg

ZIP/Postal Code

97080

Country

Germany

Facility Name

Universitätsklinikum Frankfurt, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie

City

Frankfurt

ZIP/Postal Code

60590

Country

Germany

Facility Name

Universities of Marburg and Giessen Lung Center

City

Giessen

Country

Germany

Facility Name

Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Medizinische Hochschule Hannover, Klinik für Pneumologie

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Universitätsklinikum Jena, Klinik für Anästhesiologie und Intensivmedizin

City

Jena

ZIP/Postal Code

07747

Country

Germany

Facility Name

University Hospital Marburg, Department of Anaesthesiology and Intensive Care Medicine

City

Marburg

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

24579839

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.

Results Reference

background

PubMed Identifier

19590023

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.

Results Reference

background

PubMed Identifier

22996662

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.

Results Reference

background

PubMed Identifier

16474098

Citation

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.

Results Reference

background

PubMed Identifier

22160309

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.

Results Reference

background

Learn more about this trial

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

We'll reach out to this number within 24 hrs