GI-COVID: GM-CSF Inhalation to Prevent ARDS in COVID-19 Pneumonia

Sponsor
University of Giessen (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04569877
Collaborator
(none)
63
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2
27.2
7
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Study Details

Study Description

Brief Summary

To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.

Condition or Disease Intervention/Treatment Phase
  • Drug: Molgramostim nebuliser solution
  • Other: Placebo nebuliser solution
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
63 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)
Actual Study Start Date :
Sep 24, 2020
Anticipated Primary Completion Date :
Dec 30, 2022
Anticipated Study Completion Date :
Dec 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Molgramostim nebuliser solution

300μg molgramostim nebuliser solution

Drug: Molgramostim nebuliser solution
300μg molgramostim nebuliser solution nebulised seven times within 7 days via rapid nebuliser system

Placebo Comparator: Placebo nebuliser solution

Placebo nebuliser solution

Other: Placebo nebuliser solution
Placebo nebulised seven times within 7 days via rapid nebuliser system

Outcome Measures

Primary Outcome Measures

  1. Mechanical ventilation [During 15 days]

    Need for mechanical ventilation within 15 days after randomization

Secondary Outcome Measures

  1. Clinical status of subject at day 15 and day 29 (on a 7-point ordinal scale): [At day 15 and day 29]

    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.

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [At day 0 (day before first dose), day 1-9, and day 15]

    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

  3. Oxygen supply [At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15]

    Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%

  4. Clinical parameter: temperature [Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15]

    Clinical parameter (4 times daily): temperature (°C degree)

  5. Clinical parameter: blood pressure [Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15]

    Clinical parameter (4 times daily): blood pressure (mmHg)

  6. Clinical parameter: heart beat [Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15]

    Clinical parameter (4 times daily): hear beat (beats per minute)

  7. Clinical parameter: respiratory rate [Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15]

    Clinical parameter (4 times daily): respiratory rate (breaths per minute)

  8. Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR) [Max. 48 hours before day 0 and at day 8-9]

    Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage

  9. Laboratory: C-reactive protein test [At day 0, day 1-7, day 8-9 and day 15]

    C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)

  10. Laboratory: ferritin [At day 0, day 1-7, day 8-9 and day 15]

    Ferritin test measures the amount of ferritin in the blood (ng/ml)

  11. Laboratory: Interleukin-6 [At day 0, day 1-7, day 8-9 and day 15]

    Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)

  12. Laboratory: procalcitonin [At day 0, day 1-7, day 8-9 and day 15]

    Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)

  13. Bacterial pneumonia [At day 0, day 1-7, day 8-9 and day 15]

    Occurrence of secondary bacterial pneumonia

  14. Vaso-active drugs [At day 29]

    Days on vaso-active drugs in a 29-day period

  15. Mortality [At day 29]

    All-cause mortality

  16. GM-CSF [At day 0 and day 1-7]

    GM-CSF levels in serum

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Signed informed consent form by the patient according to local regulations

  2. Man or non-pregnant woman

  3. Age ≥18 years

  4. 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 *.

  5. 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

  6. Negative serum pregnancy test in women of childbearing potentia

Exclusion Criteria:
  1. Pregnancy or breast feeding

  2. Autoimmune thrombocytopenia, myelodysplastic syndromes with > 20% marrow blast cells

  3. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim (e.g. Leucomax®) or to related compounds (e.g. Leukine®)

  4. Patient not able to use nebulizer device as well as immediately foreseeable mechanical ventilation of the patient

  5. Simultaneous participation in another clinical trial with an experimental treatment

Contacts and Locations

Locations

Site City State Country Postal Code
1 Universitätsklinikum Carl Gustav Carus Dresden Dresden Germany 01307
2 Universitätsklinikum Essen Essen Germany 45147
3 Krankenhaus Nordwest GmbH Frankfurt am Main Germany 60488
4 Universitätsklinikum Frankfurt Frankfurt am Main Germany 60590
5 Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen Gießen Germany 35392
6 Medizinische Hochschule Hannover Hannover Germany 30625
7 Universitätsklinikum Heidelberg Heidelberg Germany 69126
8 Lungenfachklinik Immenhausen Immenhausen Germany 34376
9 Sana Klinikum Offenbach Offenbach am Main Germany 63069

Sponsors and Collaborators

  • University of Giessen

Investigators

  • Principal Investigator: Susanne Herold, Prof. Dr., Universitätsklinikum Giessen und Marburg (UKGM)

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
University of Giessen
ClinicalTrials.gov Identifier:
NCT04569877
Other Study ID Numbers:
  • KKS-279
  • 2020-001654-21
First Posted:
Sep 30, 2020
Last Update Posted:
Jun 22, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by University of Giessen
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 22, 2022