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| Name | Class |
|---|---|
| Flemish institute of biotechnology (VIB) | OTHER |
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Phase IV study to evaluate the effectiveness of additional inhaled sargramostim (GM-CSF) versus standard of care on blood oxygenation in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure.
Leukine® is a yeast-derived recombinant humanized granulocyte-macrophage colony stimulating factor (rhuGM-CSF, sargramostim) and the only FDA approved GM-CSF. GMCSF, a pleiotropic cytokine, is an important leukocyte growth factor known to play a key role in hematopoiesis, effecting the growth and maturation of multiple cell lineages as well as the functional activities of these cells in antigen presentation and cell mediated immunity.
Leukine inhalation or intravenous administration, as an adjuvant therapy, may confer benefit to patients with ARDS (Acute Respiratory Distress Syndrome) due to COVID-19 exposure, who are at significant risk of mortality. While there is no active IND (Investigational New Drug) for Leukine in the proposed patient population, Leukine is being studied in Fase II as an adjuvant therapy in the management of life-threatening infections to boost the hosts innate immune response to fight infection, reduce the risk of secondary infection, and in varied conditions as prevention of infection during critical illness. Inhaled Leukine has also been successfully used as primary therapy to improve oxygenation in patients with disordered gas exchange in the lungs. We propose that based on preclinical and clinical data, Leukine inhalation, as an adjuvant therapy, has an acceptable benefit-risk for use in patients with hypoxic respiratory failure and ARDS due to COVID-19 exposure, who are at significant risk of mortality.
Confirmed COVID19 patients with hypoxic respiratory failure (saturation below 93% on minimal 2 l/min O2) will be randomized to receive sargramostim 125mcg twice daily for 5 days as a nebulized inhalation on top of standard of care, or to receive standard of care treatment. Upon progression of disease requiring initiation of mechanical ventilatory support within the 5 day period, in patients in the active group, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment. In the control group progressive disease requiring mechanical ventilatory support, from day 6 onwards, the treating physician will have the option to initiate IV sargramostim 125mcg/m2 body surface area for 5 days. Safety data, including blood leukocyte counts, will be collected in all patients. Efficacy data will also be collected and will include arterial blood gases, oxygenation parameters, need for ventilation, lung compliance, organ function, radiographic changes, ferritin levels, etc. as well as occurrence of secondary bacterial infections.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active sargramostim treatment group | Active Comparator | Inhaled sargramostim 125mcg twice daily for 5 days on top of standard of care. Upon progression to ARDS and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment |
|
| Control group | Placebo Comparator | standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sargramostim | Drug | Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in Oxygenation | Mean Change from Baseline in PaO2/FiO2 on Day 6 or hospital discharge, whichever came first | on Day 6 or hospital discharge, whichever came first |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in 6-point Ordinal Scale for Clinical Improvement | The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal Membrane Oxygenation) ; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome |
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Inclusion Criteria:
Recent (≤2weeks prior to Randomization) confident diagnosis of COVID-19 confirmed by antigen detection and/or PCR (Polymerase Chain Reaction), and/or seroconversion or any other emerging and validated diagnostic test
In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.
Presence of acute hypoxic respiratory failure defined as (either or both)
Admitted to specialized COVID-19 ward
Age 18-80
Male or Female
Willing to provide informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bart Lambrecht | University Hospital, Ghent | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AZ Sint Jan Brugge | Bruges | 8000 | Belgium | |||
| University Hospital Ghent |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36459994 | Derived | Bosteels C, Van Damme KFA, De Leeuw E, Declercq J, Maes B, Bosteels V, Hoste L, Naesens L, Debeuf N, Deckers J, Cole B, Pardons M, Weiskopf D, Sette A, Weygaerde YV, Malfait T, Vandecasteele SJ, Demedts IK, Slabbynck H, Allard S, Depuydt P, Van Braeckel E, De Clercq J, Martens L, Dupont S, Seurinck R, Vandamme N, Haerynck F, Roychowdhury DF, Vandekerckhove L, Guilliams M, Tavernier SJ, Lambrecht BN. Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment. Cell Rep Med. 2022 Dec 20;3(12):100833. doi: 10.1016/j.xcrm.2022.100833. Epub 2022 Nov 15. | |
| 32559419 |
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87 patients were screened in the period from 25-mar-2020 till 29-sep-2020. 87 patients were included, 81 patients were randomised, 79 patients completed the study
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Sargramostim Treatment Group | Inhaled sargramostim 125mcg twice daily for 5 days on top of standard of care. Upon progression to ARDS and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration |
| FG001 | Control Group | standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration Control: Standard of care |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Sargramostim Treatment Group | Inhaled sargramostim 125mcg twice daily for 5 days on top of standard of care. Upon progression to ARDS and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Improvement in Oxygenation | Mean Change from Baseline in PaO2/FiO2 on Day 6 or hospital discharge, whichever came first | 73 of the 81 patients reached the evaluable primary endpoint. 2 patient discontinued prematurely, 3 patients refused arterial puncture at day 6, 3 patients were excluded because they had a negative P(A-a)O2 gradient at randomization or day 6, signifying an error in FiO2 recording. | Posted | Mean | Standard Deviation | ratio | on Day 6 or hospital discharge, whichever came first |
|
Timeframe for reporting adverse events: through study completion, an average of 5 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active Sargramostim Treatment Group | Inhaled sargramostim 125mcg twice daily for 5 days on top of standard of care. Upon progression to ARDS and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125mcg/m2 body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thormboembolic event | Vascular disorders | Non-systematic Assessment | pulmonary embolism |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac disorder | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Cedric Bosteels | UZ Gent | +3293325909 | cedric.bosteels@ugent.be |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 7, 2021 | Mar 3, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 5, 2021 | Jun 20, 2022 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D055371 | Acute Lung Injury |
| D000860 | Hypoxia |
| D012128 | Respiratory Distress Syndrome |
| D045169 | Severe Acute Respiratory Syndrome |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C081222 | sargramostim |
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|
| Control | Other | Standard of care |
|
| at Baseline, at Day 6 |
| Number of Days in Hospital | through study completion, an average of 5 months |
| Number of Participants With Nosocomial Infection no./Total no (%) | during hospital admission (up to 28 days) |
| Death | at 28 days |
| Number of Participants Progressed to Mechanical Ventilation and/or ARDS | during hospital admission (up to 28 days) |
| Time to Clinical Sign Score < 6 for at Least 24h | Clinical Sign score (0-18) by scoring 6 clinical signs from 0 to 3 (0 = absent, 1 = mild, 2 = moderate and 3 = severe): Fever (0 = <37°C; 1 = 37.1-38°C; 2 = 38.1-39°C; 3 = >39°C) last 24h; Cough; Fatigue; Shortness of breath; Diarrhea; Body pain. Higher values represent a worse outcome | During hospital admission (up to 28 days) |
| Change in Clinical Sign Score | Clinical Sign score (0-18) by scoring 6 clinical signs from 0 to 3 (0 = absent, 1 = mild, 2 = moderate and 3 = severe): Fever (0 = <37°C; 1 = 37.1-38°C; 2 = 38.1-39°C; 3 = >39°C) last 24h; Cough; Fatigue; Shortness of breath; Diarrhea; Body pain. Higher values represent a worse outcome. | at baseline, at day 6 |
| Change in (National Early Warning Score2) NEWS2 Score | The NEWS2 score standardises the assessment and response to acute illness. Six physiological parameters form the basis of the scoring system: respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new confusion, temperature. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk | at baseline, at day 6 |
| Change in Sequential Organ Failure Assessment (SOFA Score) | The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points. | at baseline, at day 6 |
| Change in Ferritin Level | at baseline, at day 6 |
| Change in D-dimer Level | at baseline, at day 6 |
| Change in CRP Level | at baseline, at day 6 |
| Change in Lymphocyte Count | at baseline, at day 6 |
| Change in Eosinophil Count | at baseline, at day 6 |
| HRCT (High-Resolution Computed Tomography) Fibrosis Score | The HRCT fibrosis score is a subjective assessment of the overall extent of normal attenuation, reticular abnormalities, honeycombing and traction bronchiectasis . The HRCT findings are graded on a scale of 1-4 based on the classification system: 1. normal attenuation; 2. reticular abnormality; 3. traction bronchiectasis; and 4. honeycombing. The presence of each of the above four HRCT findings is assessed independently in three (upper, middle and lower) zones of each lung. The extent of each HRCT finding was determined by visually estimating the percentage (to the nearest 5%) of parenchymal involvement in each zone. The score for each zone was calculated by multiplying the percentage of the area by the grading scale score (i.e. 1. normal attenuation; 2. reticular abnormality; 3. traction bronchiectasis; and 4. honeycombing). The six zone scores were averaged to determine the total score for each patient. The score ranges from 100 to 400, higher values represent more fibrosis. | at follow-up, 10-20 weeks after day 10 or discharge, whichever comes first |
| Ghent |
| 9000 |
| Belgium |
| UZ Brussel | Jette | 1090 | Belgium |
| AZ Delta Roeselare | Roeselare | 8800 | Belgium |
| Derived |
| Mehta P, Porter JC, Manson JJ, Isaacs JD, Openshaw PJM, McInnes IB, Summers C, Chambers RC. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities. Lancet Respir Med. 2020 Aug;8(8):822-830. doi: 10.1016/S2213-2600(20)30267-8. Epub 2020 Jun 16. |
| 32503663 | Derived | Bosteels C, Maes B, Van Damme K, De Leeuw E, Declercq J, Delporte A, Demeyere B, Vermeersch S, Vuylsteke M, Willaert J, Bolle L, Vanbiervliet Y, Decuypere J, Libeer F, Vandecasteele S, Peene I, Lambrecht B. Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 5;21(1):491. doi: 10.1186/s13063-020-04451-7. |
| BG001 | Control Group | standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration Control: Standard of care |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Comorbidity at baseline | Count of Participants | Participants |
|
| Smoking status at baseline | smoking status at baseline | Count of Participants | Participants |
|
| Concomitant medication at randomization | Count of Participants | Participants |
|
| 6-category ordinal scale at baseline | 6-category ordinal scale at baseline | Count of Participants | Participants |
|
| Lab values - C-reactive protein at baseline | Median | Inter-Quartile Range | mg/L |
|
| Biomarkers in serum - IL1RA at baseline | Median | Inter-Quartile Range | ng/mL |
|
| Oxygenation - PaO2/FiO2 ratio at baseline | PaO2/FiO2 ratio is the ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2; PaO2/FiO2). | Median | Inter-Quartile Range | ratio |
|
| Oxygenation - P(A-a)O2 gradient at baseline | partial pressure of oxygen alveolar- arterial ( (P(A-a)O2 gradient) | Median | Inter-Quartile Range | mmHg |
|
| Lab values - eosinophil count at baseline | Median | Inter-Quartile Range | cells x10^9/L |
|
| Lab values - lymphocyte count at baseline | Median | Inter-Quartile Range | cells x10^9/L |
|
| Lab values - ferritin at baseline | Median | Inter-Quartile Range | mcg/L |
|
| Lab values - D-dimer at baseline | Median | Inter-Quartile Range | nmol/L |
|
| Lab values - lactate dehydrogenase at baseline | Median | Inter-Quartile Range | ukat/L |
|
| Lab values - aspartate aminotransferase at baseline | Median | Inter-Quartile Range | ukat/L |
|
| Lab values - alanine aminotransferase at baseline | alanine aminotransferase at baseline | Median | Inter-Quartile Range | ukat/L |
|
| Lab values - creatinine at baseline | Median | Inter-Quartile Range | micromol/L |
|
| Biomarkers in serum - IL-6 at baseline | Median | Inter-Quartile Range | pg/mL |
|
| Biomarkers in serum - IL-18 at baseline | Median | Inter-Quartile Range | pg/mL |
|
| Biomarkers in serum -C5a at baseline | Median | Inter-Quartile Range | ng/mL |
|
| Biomarkers in serum - GM-CSF at baseline | Median | Inter-Quartile Range | fg/mL |
|
| Biomarkers in serum - TNF at baseline | Median | Inter-Quartile Range | pg/mL |
|
| Body Mass Index (BMI) at baseline | Median | Inter-Quartile Range | kg/m^2 |
|
| Days since symptom onset at baseline | Median | Inter-Quartile Range | day |
|
| Days since hospitalization at baseline | Median | Inter-Quartile Range | days |
|
| Biomarkers in serum - IL-8 at baseline | Median | Inter-Quartile Range | pg/mL |
|
| OG001 | Control Group | standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration Control: Standard of care |
|
|
| Secondary | Mean Change in 6-point Ordinal Scale for Clinical Improvement | The 6-point ordinal scale for clinical improvement is defined as 1 = Death; 2 = Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal Membrane Oxygenation) ; 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4 = Hospitalized, requiring supplemental oxygen; 5 = Hospitalized, not requiring supplemental oxygen; 6 = Not hospitalized. A higher score represent a better outcome | Posted | Mean | Standard Deviation | units on a scale | at Baseline, at Day 6 |
|
|
|
| Secondary | Number of Days in Hospital | Posted | Median | 95% Confidence Interval | days | through study completion, an average of 5 months |
|
|
|
| Secondary | Number of Participants With Nosocomial Infection no./Total no (%) | Posted | Count of Participants | Participants | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Death | Posted | Count of Participants | Participants | at 28 days |
|
|
|
| Secondary | Number of Participants Progressed to Mechanical Ventilation and/or ARDS | Posted | Count of Participants | Participants | during hospital admission (up to 28 days) |
|
|
|
| Secondary | Time to Clinical Sign Score < 6 for at Least 24h | Clinical Sign score (0-18) by scoring 6 clinical signs from 0 to 3 (0 = absent, 1 = mild, 2 = moderate and 3 = severe): Fever (0 = <37°C; 1 = 37.1-38°C; 2 = 38.1-39°C; 3 = >39°C) last 24h; Cough; Fatigue; Shortness of breath; Diarrhea; Body pain. Higher values represent a worse outcome | Posted | Median | 95% Confidence Interval | Days | During hospital admission (up to 28 days) |
|
|
|
| Secondary | Change in Clinical Sign Score | Clinical Sign score (0-18) by scoring 6 clinical signs from 0 to 3 (0 = absent, 1 = mild, 2 = moderate and 3 = severe): Fever (0 = <37°C; 1 = 37.1-38°C; 2 = 38.1-39°C; 3 = >39°C) last 24h; Cough; Fatigue; Shortness of breath; Diarrhea; Body pain. Higher values represent a worse outcome. | Posted | Mean | Standard Deviation | score on a scale | at baseline, at day 6 |
|
|
|
| Secondary | Change in (National Early Warning Score2) NEWS2 Score | The NEWS2 score standardises the assessment and response to acute illness. Six physiological parameters form the basis of the scoring system: respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new confusion, temperature. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk | Posted | Mean | Standard Deviation | score on a scale | at baseline, at day 6 |
|
|
|
| Secondary | Change in Sequential Organ Failure Assessment (SOFA Score) | The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems). Score ranges from 0 (best) to 24 (worst) points. | Posted | Mean | Standard Deviation | score on a scale | at baseline, at day 6 |
|
|
|
| Secondary | Change in Ferritin Level | Posted | Median | 95% Confidence Interval | mcg/L | at baseline, at day 6 |
|
|
|
| Secondary | Change in D-dimer Level | Posted | Median | 95% Confidence Interval | nmol/L | at baseline, at day 6 |
|
|
|
| Secondary | Change in CRP Level | Posted | Median | 95% Confidence Interval | mg/L | at baseline, at day 6 |
|
|
|
| Secondary | Change in Lymphocyte Count | Posted | Median | 95% Confidence Interval | *cells* x10^9/L | at baseline, at day 6 |
|
|
|
| Secondary | Change in Eosinophil Count | Posted | Median | 95% Confidence Interval | *cells* x10^9/L | at baseline, at day 6 |
|
|
|
| Secondary | HRCT (High-Resolution Computed Tomography) Fibrosis Score | The HRCT fibrosis score is a subjective assessment of the overall extent of normal attenuation, reticular abnormalities, honeycombing and traction bronchiectasis . The HRCT findings are graded on a scale of 1-4 based on the classification system: 1. normal attenuation; 2. reticular abnormality; 3. traction bronchiectasis; and 4. honeycombing. The presence of each of the above four HRCT findings is assessed independently in three (upper, middle and lower) zones of each lung. The extent of each HRCT finding was determined by visually estimating the percentage (to the nearest 5%) of parenchymal involvement in each zone. The score for each zone was calculated by multiplying the percentage of the area by the grading scale score (i.e. 1. normal attenuation; 2. reticular abnormality; 3. traction bronchiectasis; and 4. honeycombing). The six zone scores were averaged to determine the total score for each patient. The score ranges from 100 to 400, higher values represent more fibrosis. | Posted | Mean | 95% Confidence Interval | score on a scale | at follow-up, 10-20 weeks after day 10 or discharge, whichever comes first |
|
|
|
| 4 |
| 40 |
| 6 |
| 40 |
| 22 |
| 40 |
| EG001 | Control Group | standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards, will have the option (clinician's decision) to initiate IV sargramostim 125mcg/m2 body surface area once daily for 5 days Sargramostim: Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration Control: Standard of care | 8 | 41 | 6 | 41 | 20 | 41 |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Ventilator associated pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Aspergillus infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Respiratory deterioration due to underlying MPO-ANCA vasculitis and aspergillosis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Increasing hypoxemia due to COVID-19 |
|
| Cerebrovascular accident | Nervous system disorders | Non-systematic Assessment |
|
| Presyncope | Nervous system disorders | Non-systematic Assessment | Progressive symptomatic orthostatism with presyncope |
|
| Persistent catatonic state and neurological deficits | Psychiatric disorders | Non-systematic Assessment |
|
| Invasive aspergillosis | Infections and infestations | Non-systematic Assessment |
|
| Multi-bacterial bacteremia causing hemorrhagic shock | Infections and infestations | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
|
| Infectious disorder (not COVID-19) | Infections and infestations | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D055370 | Lung Injury |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |