Trial Outcomes & Findings for Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC) (NCT NCT04326920)
NCT ID: NCT04326920
Last Updated: 2022-11-16
Results Overview
Mean Change from Baseline in PaO2/FiO2 on Day 6 or hospital discharge, whichever came first
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
87 participants
Primary outcome timeframe
on Day 6 or hospital discharge, whichever came first
Results posted on
2022-11-16
Participant Flow
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
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
40
|
41
|
|
Overall Study
COMPLETED
|
40
|
39
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC)
Baseline characteristics by cohort
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Comorbidity at baseline
Arterial hypertension
|
7 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
55 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Age, Continuous
|
59 years
n=99 Participants
|
60 years
n=107 Participants
|
60 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
34 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
73 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Arabian
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Comorbidity at baseline
Diabetes mellitus
|
9 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Comorbidity at baseline
Cardiovascular disease
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Comorbidity at baseline
Chronic kidney disease
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Comorbidity at baseline
Severe liver disease
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Comorbidity at baseline
Chronic lung disease
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Comorbidity at baseline
Cancer
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Comorbidity at baseline
Patients without reported comorbidities
|
22 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Smoking status at baseline
Current
|
0 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Smoking status at baseline
Former
|
18 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Smoking status at baseline
Never
|
22 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Concomitant medication at randomization
Glucocorticoids
|
11 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Concomitant medication at randomization
Antiviral drugs (Remdesivir)
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Concomitant medication at randomization
Hydroxychloroquine
|
24 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
|
Concomitant medication at randomization
Antibiotics
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Concomitant medication at randomization
Patients without reported concomitant medication
|
1 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
6-category ordinal scale at baseline
5 Hospitalized, no supplemental oxygen
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
6-category ordinal scale at baseline
4 Hospitalized, supplemental oxygen
|
38 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
71 Participants
n=206 Participants
|
|
6-category ordinal scale at baseline
3 Hospitalized, Non Invasive Mechanical Ventilation (NIMV) or High Flow Oxygen Device (HFOD)
|
1 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Lab values - C-reactive protein at baseline
|
73.2 mg/L
n=99 Participants
|
83 mg/L
n=107 Participants
|
74.5 mg/L
n=206 Participants
|
|
Biomarkers in serum - IL1RA at baseline
|
839.3 ng/mL
n=99 Participants
|
1288 ng/mL
n=107 Participants
|
1162 ng/mL
n=206 Participants
|
|
Oxygenation - PaO2/FiO2 ratio at baseline
|
291.5 ratio
n=99 Participants
|
297 ratio
n=107 Participants
|
295 ratio
n=206 Participants
|
|
Oxygenation - P(A-a)O2 gradient at baseline
|
50.15 mmHg
n=99 Participants
|
45.55 mmHg
n=107 Participants
|
47.65 mmHg
n=206 Participants
|
|
Lab values - eosinophil count at baseline
|
0.01 cells x10^9/L
n=99 Participants
|
0.02 cells x10^9/L
n=107 Participants
|
0.02 cells x10^9/L
n=206 Participants
|
|
Lab values - lymphocyte count at baseline
|
1.08 cells x10^9/L
n=99 Participants
|
0.88 cells x10^9/L
n=107 Participants
|
1.00 cells x10^9/L
n=206 Participants
|
|
Lab values - ferritin at baseline
|
736.5 mcg/L
n=99 Participants
|
721 mcg/L
n=107 Participants
|
721 mcg/L
n=206 Participants
|
|
Lab values - D-dimer at baseline
|
4.36 nmol/L
n=99 Participants
|
3.61 nmol/L
n=107 Participants
|
3.81 nmol/L
n=206 Participants
|
|
Lab values - lactate dehydrogenase at baseline
|
4.98 ukat/L
n=99 Participants
|
5.98 ukat/L
n=107 Participants
|
5.26 ukat/L
n=206 Participants
|
|
Lab values - aspartate aminotransferase at baseline
|
0.62 ukat/L
n=99 Participants
|
0.65 ukat/L
n=107 Participants
|
0.65 ukat/L
n=206 Participants
|
|
Lab values - alanine aminotransferase at baseline
|
0.59 ukat/L
n=99 Participants
|
0.57 ukat/L
n=107 Participants
|
0.58 ukat/L
n=206 Participants
|
|
Lab values - creatinine at baseline
|
75.14 micromol/L
n=99 Participants
|
78.68 micromol/L
n=107 Participants
|
77.35 micromol/L
n=206 Participants
|
|
Biomarkers in serum - IL-6 at baseline
|
11.47 pg/mL
n=99 Participants
|
11.54 pg/mL
n=107 Participants
|
11.54 pg/mL
n=206 Participants
|
|
Biomarkers in serum - IL-18 at baseline
|
101.3 pg/mL
n=99 Participants
|
150.7 pg/mL
n=107 Participants
|
131.00 pg/mL
n=206 Participants
|
|
Biomarkers in serum -C5a at baseline
|
11.18 ng/mL
n=99 Participants
|
8.83 ng/mL
n=107 Participants
|
9.94 ng/mL
n=206 Participants
|
|
Biomarkers in serum - GM-CSF at baseline
|
9.13 fg/mL
n=99 Participants
|
9.12 fg/mL
n=107 Participants
|
9.12 fg/mL
n=206 Participants
|
|
Biomarkers in serum - TNF at baseline
|
16.32 pg/mL
n=99 Participants
|
14.77 pg/mL
n=107 Participants
|
14.99 pg/mL
n=206 Participants
|
|
Body Mass Index (BMI) at baseline
|
28.6 kg/m^2
n=99 Participants
|
27.6 kg/m^2
n=107 Participants
|
28.0 kg/m^2
n=206 Participants
|
|
Days since symptom onset at baseline
|
11 day
n=99 Participants
|
10 day
n=107 Participants
|
11.0 day
n=206 Participants
|
|
Days since hospitalization at baseline
|
3 days
n=99 Participants
|
3 days
n=107 Participants
|
3.0 days
n=206 Participants
|
|
Biomarkers in serum - IL-8 at baseline
|
22.51 pg/mL
n=99 Participants
|
27.44 pg/mL
n=107 Participants
|
23.99 pg/mL
n=206 Participants
|
PRIMARY outcome
Timeframe: on Day 6 or hospital discharge, whichever came firstPopulation: 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.
Mean Change from Baseline in PaO2/FiO2 on Day 6 or hospital discharge, whichever came first
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=35 Participants
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
|
Control Group
n=38 Participants
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
|
|---|---|---|
|
Improvement in Oxygenation
|
25.7 ratio
Standard Deviation 85.3
|
29.7 ratio
Standard Deviation 71.88
|
SECONDARY outcome
Timeframe: at Baseline, at Day 6The 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
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Mean Change in 6-point Ordinal Scale for Clinical Improvement
|
0.3 units on a scale
Standard Deviation 1.0
|
0.3 units on a scale
Standard Deviation 1.0
|
SECONDARY outcome
Timeframe: through study completion, an average of 5 monthsOutcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Number of Days in Hospital
|
8.5 days
Interval 6.0 to 12.0
|
9.0 days
Interval 7.0 to 14.0
|
SECONDARY outcome
Timeframe: during hospital admission (up to 28 days)Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Number of Participants With Nosocomial Infection no./Total no (%)
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: at 28 daysOutcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Death
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: during hospital admission (up to 28 days)Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Number of Participants Progressed to Mechanical Ventilation and/or ARDS
|
7 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: During hospital admission (up to 28 days)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
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Time to Clinical Sign Score < 6 for at Least 24h
|
2.0 Days
Interval 1.0 to 3.0
|
3.0 Days
Interval 1.0 to 6.0
|
SECONDARY outcome
Timeframe: at baseline, at day 6Clinical 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.
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in Clinical Sign Score
|
-2.0 score on a scale
Standard Deviation 3.1
|
-2.2 score on a scale
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: at baseline, at day 6The 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
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in (National Early Warning Score2) NEWS2 Score
|
-0.6 score on a scale
Standard Deviation 3.1
|
-0.4 score on a scale
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: at baseline, at day 6The 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.
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in Sequential Organ Failure Assessment (SOFA Score)
|
-0.5 score on a scale
Standard Deviation 1.5
|
-0.4 score on a scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: at baseline, at day 6Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in Ferritin Level
|
-90 mcg/L
Interval -150.0 to 34.0
|
-112 mcg/L
Interval -259.0 to 118.0
|
SECONDARY outcome
Timeframe: at baseline, at day 6Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in D-dimer Level
|
-0.71 nmol/L
Interval -1.79 to 1.33
|
-0.44 nmol/L
Interval -2.9 to 2.46
|
SECONDARY outcome
Timeframe: at baseline, at day 6Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in CRP Level
|
-43.6 mg/L
Interval -69.8 to -21.7
|
-43.1 mg/L
Interval -73.8 to -22.8
|
SECONDARY outcome
Timeframe: at baseline, at day 6Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in Lymphocyte Count
|
0.45 *cells* x10^9/L
Interval 0.18 to 0.7
|
0.20 *cells* x10^9/L
Interval 0.02 to 0.56
|
SECONDARY outcome
Timeframe: at baseline, at day 6Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
Change in Eosinophil Count
|
0.100 *cells* x10^9/L
Interval 0.01 to 0.16
|
0.005 *cells* x10^9/L
Interval 0.0 to 0.073
|
SECONDARY outcome
Timeframe: at follow-up, 10-20 weeks after day 10 or discharge, whichever comes firstThe 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.
Outcome measures
| Measure |
Active Sargramostim Treatment Group
n=40 Participants
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
|
Control Group
n=41 Participants
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
|
|---|---|---|
|
HRCT (High-Resolution Computed Tomography) Fibrosis Score
|
100.8 score on a scale
Interval 100.0 to 102.5
|
102.5 score on a scale
Interval 100.0 to 105.8
|
Adverse Events
Active Sargramostim Treatment Group
Serious events: 6 serious events
Other events: 22 other events
Deaths: 4 deaths
Control Group
Serious events: 6 serious events
Other events: 20 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Active Sargramostim Treatment Group
n=40 participants at risk
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
|
Control Group
n=41 participants at risk
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
|
|---|---|---|
|
Vascular disorders
Thormboembolic event
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Ventilator associated pneumonia
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Aspergillus infection
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory deterioration due to underlying MPO-ANCA vasculitis and aspergillosis
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Nervous system disorders
Cerebrovascular accident
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Nervous system disorders
Presyncope
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Psychiatric disorders
Persistent catatonic state and neurological deficits
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Infections and infestations
Invasive aspergillosis
|
2.5%
1/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Infections and infestations
Multi-bacterial bacteremia causing hemorrhagic shock
|
0.00%
0/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
2.4%
1/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
Other adverse events
| Measure |
Active Sargramostim Treatment Group
n=40 participants at risk
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
|
Control Group
n=41 participants at risk
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
|
|---|---|---|
|
Cardiac disorders
Cardiac disorder
|
5.0%
2/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
7.3%
3/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
20.0%
8/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
4.9%
2/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Gastrointestinal disorders
Constipation
|
7.5%
3/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
14.6%
6/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Renal and urinary disorders
Acute kidney injury
|
5.0%
2/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
0.00%
0/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
|
Infections and infestations
Infectious disorder (not COVID-19)
|
17.5%
7/40 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
22.0%
9/41 • Timeframe for reporting adverse events: through study completion, an average of 5 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place