Back to resultsGM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)
Primary Purpose
Severe Acute Respiratory Syndrome (SARS) Pneumonia, COVID-19 Pneumonia
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Molgramostim nebuliser solution
Placebo nebuliser solution
Sponsored by
About this trial
This is an interventional treatment trial for Severe Acute Respiratory Syndrome (SARS) Pneumonia focused on measuring GM-CSF, COVID-19, ARDS
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form by the patient according to local regulations
- Man or non-pregnant woman
- Age ≥18 years
- Willingness of patients with reproductive potential to use highly effective contraceptive methods by practicing abstinence or by using at least two methods of birth control from the date of consent to the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used *.
- Lab-confirmed COVID-19 pneumonia where pneumonia is diagnosed by radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR clinical assessment (evidence of rales/crackles on exam) AND pulse oximeter oxygen saturation ≤ 94% at room air in patients that do not have chronic hypoxia; or less than their baseline oxygenation in patients that suffer from chronic hypoxia
- Negative serum pregnancy test in women of childbearing potentia
Exclusion Criteria:
- Pregnancy or breast feeding
- Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells
- History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®)
- Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient
- Simultaneous participation in another clinical trial with an experimental treatment
Sites / Locations
- Universitätsklinikum Carl Gustav Carus Dresden
- Universitätsklinikum Essen
- Krankenhaus Nordwest GmbH
- Universitätsklinikum Frankfurt
- Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen
- Medizinische Hochschule Hannover
- Universitätsklinikum Heidelberg
- Lungenfachklinik Immenhausen
- Sana Klinikum Offenbach
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Molgramostim nebuliser solution
Placebo nebuliser solution
Arm Description
300μg molgramostim nebuliser solution
Placebo nebuliser solution
Outcomes
Primary Outcome Measures
Mechanical ventilation
Need for mechanical ventilation within 15 days after randomization
Secondary Outcome Measures
Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale):
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] will be measured at day 0 (day before first dose), day 1-9, and day 15
Oxygen supply
Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%
Clinical parameter: temperature
Clinical parameter (4 times daily): temperature (°C degree)
Clinical parameter: blood pressure
Clinical parameter (4 times daily): blood pressure (mmHg)
Clinical parameter: heart beat
Clinical parameter (4 times daily): hear beat (beats per minute)
Clinical parameter: respiratory rate
Clinical parameter (4 times daily): respiratory rate (breaths per minute)
Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)
Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage
Laboratory: C-reactive protein test
C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)
Laboratory: ferritin
Ferritin test measures the amount of ferritin in the blood (ng/ml)
Laboratory: Interleukin-6
Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)
Laboratory: procalcitonin
Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)
Bacterial pneumonia
Occurrence of secondary bacterial pneumonia
Vaso-active drugs
Days on vaso-active drugs in a 29-day period
Mortality
All-cause mortality
GM-CSF
GM-CSF levels in serum
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04569877
Brief Title
GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia
Acronym
GI-COVID
Official Title
Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 24, 2020 (Actual)
Primary Completion Date
June 21, 2022 (Actual)
Study Completion Date
September 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Giessen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.
Detailed Description
COVID-19 pneumonia is induced by the newly emerging pandemic Severe acute respiratory Syndrome (SARS) coronavirus 2 and results in progression to the acute respiratory distress syndrome (ARDS). Apart from protective ventilation, fluid restriction, prone positioning and extracorporeal membrane oxygenation (ECMO), no specific therapeutic options exist to treat this devastating disease with a mortality rate of up to 50%. The growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) is widely recognized to promote differentiation and mobilization of different myeloid leukocyte subsets including neutrophils, tissue macrophages/dendritic cells or their circulating precursors. GM-CSF was found to be crucial for alveolar epithelial repair following hyperoxic and inflammatory lung injury.The aim of the current trial is to prevent progression to ARDS in COVID-19 pneumonia patients by preemptive GM-CSF Inhalation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Acute Respiratory Syndrome (SARS) Pneumonia, COVID-19 Pneumonia
Keywords
GM-CSF, COVID-19, ARDS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Molgramostim nebuliser solution
Arm Type
Experimental
Arm Description
300μg molgramostim nebuliser solution
Arm Title
Placebo nebuliser solution
Arm Type
Placebo Comparator
Arm Description
Placebo nebuliser solution
Intervention Type
Drug
Intervention Name(s)
Molgramostim nebuliser solution
Intervention Description
300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system
Intervention Type
Other
Intervention Name(s)
Placebo nebuliser solution
Intervention Description
Placebo nebulised seven times within 7 days via rapid nebuliser system
Primary Outcome Measure Information:
Title
Mechanical ventilation
Description
Need for mechanical ventilation within 15 days after randomization
Time Frame
During 15 days
Secondary Outcome Measure Information:
Title
Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale):
Description
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
Time Frame
At day 15 and day 29
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] will be measured at day 0 (day before first dose), day 1-9, and day 15
Time Frame
At day 0 (day before first dose), day 1-9, and day 15
Title
Oxygen supply
Description
Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%
Time Frame
At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15
Title
Clinical parameter: temperature
Description
Clinical parameter (4 times daily): temperature (°C degree)
Time Frame
Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
Title
Clinical parameter: blood pressure
Description
Clinical parameter (4 times daily): blood pressure (mmHg)
Time Frame
Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
Title
Clinical parameter: heart beat
Description
Clinical parameter (4 times daily): hear beat (beats per minute)
Time Frame
Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
Title
Clinical parameter: respiratory rate
Description
Clinical parameter (4 times daily): respiratory rate (breaths per minute)
Time Frame
Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15
Title
Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)
Description
Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage
Time Frame
Max. 48 hours before day 0 and at day 8-9
Title
Laboratory: C-reactive protein test
Description
C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)
Time Frame
At day 0, day 1-7, day 8-9 and day 15
Title
Laboratory: ferritin
Description
Ferritin test measures the amount of ferritin in the blood (ng/ml)
Time Frame
At day 0, day 1-7, day 8-9 and day 15
Title
Laboratory: Interleukin-6
Description
Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)
Time Frame
At day 0, day 1-7, day 8-9 and day 15
Title
Laboratory: procalcitonin
Description
Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)
Time Frame
At day 0, day 1-7, day 8-9 and day 15
Title
Bacterial pneumonia
Description
Occurrence of secondary bacterial pneumonia
Time Frame
At day 0, day 1-7, day 8-9 and day 15
Title
Vaso-active drugs
Description
Days on vaso-active drugs in a 29-day period
Time Frame
At day 29
Title
Mortality
Description
All-cause mortality
Time Frame
At day 29
Title
GM-CSF
Description
GM-CSF levels in serum
Time Frame
At day 0 and day 1-7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent form by the patient according to local regulations
Man or non-pregnant woman
Age ≥18 years
Willingness of patients with reproductive potential to use highly effective contraceptive methods by practicing abstinence or by using at least two methods of birth control from the date of consent to the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used *.
Lab-confirmed COVID-19 pneumonia where pneumonia is diagnosed by radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR clinical assessment (evidence of rales/crackles on exam) AND pulse oximeter oxygen saturation ≤ 94% at room air in patients that do not have chronic hypoxia; or less than their baseline oxygenation in patients that suffer from chronic hypoxia
Negative serum pregnancy test in women of childbearing potentia
Exclusion Criteria:
Pregnancy or breast feeding
Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells
History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®)
Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient
Simultaneous participation in another clinical trial with an experimental treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Herold, Prof. Dr.
Organizational Affiliation
Universitätsklinikum Giessen und Marburg (UKGM)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Krankenhaus Nordwest GmbH
City
Frankfurt am Main
ZIP/Postal Code
60488
Country
Germany
Facility Name
Universitätsklinikum Frankfurt
City
Frankfurt am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
Lungenfachklinik Immenhausen
City
Immenhausen
ZIP/Postal Code
34376
Country
Germany
Facility Name
Sana Klinikum Offenbach
City
Offenbach am Main
ZIP/Postal Code
63069
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Study protocol will be provided after publication
IPD Sharing Time Frame
3 Months after publication
IPD Sharing Access Criteria
Central server
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GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia
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