iLeukPulm: Study of Sargramostim in Patients With COVID-19

• Sponsor: Partner Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04411680
• Collaborator: United States Department of Defense (U.S. Fed)
• Enrollment: 123
• Locations: 11
• Arms: 2
• Actual Duration (Months): 9
• Patients Per Site: 11.2
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this research is to find out if a drug (sargramostim) also known as Leukine® could help patient recover faster from COVID-19. Sargramostim may help the lungs recover from the effects of COVID-19, and this research study will help to find this out.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; SARS-CoV-2	Drug: Sargramostim; Drug: Standard of care	Phase 2

Detailed Description

This Phase 2 study is designed as a proof of concept study and will randomize 2:1 approximately 120 patients with COVID-19 associated acute hypoxemia: of which 80 patients will receive sargramostim plus standard of care, and 40 patients who will receive standard of care alone. The aim of the study is to determine if inhaled sargramostim, as an adjunct to institutional standard of care, improves clinical outcomes in patients with COVID-19-associated acute hypoxemia. All patients on the sargramostim arm will be treated with 125 mcg inhaled sargramostim twice daily for 5 days, in addition to institutional standard of care. If required, upon progression to an invasive mechanical ventilator, administration of sargramostim may be delivered by intravenous infusion to complete a total of 5 days (including days delivered via inhalation).

GM-CSF is a critical cytokine for healthy pulmonary function and is necessary for the maturation and maintenance of alveolar macrophages. Preclinical studies have shown GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages for their health and normal functioning. Clinical studies of sargramostim in patients with severe sepsis and respiratory dysfunction or acute respiratory distress syndrome have shown improvements in oxygenation and lung compliance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This Phase 2, randomized, open-label study will enroll approximately 120 patients with COVID-19 associated acute hypoxemia. It is a randomized 2:1 study to evaluate sargramostim treatment plus institutional standard of care compared to institutional standard of care alone.This Phase 2, randomized, open-label study will enroll approximately 120 patients with COVID-19 associated acute hypoxemia. It is a randomized 2:1 study to evaluate sargramostim treatment plus institutional standard of care compared to institutional standard of care alone.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia
• Actual Study Start Date: Aug 18, 2020
• Actual Primary Completion Date: Mar 2, 2021
• Actual Study Completion Date: May 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sargramostim Arm Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19	Drug: Sargramostim; Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period.; Other Names: Leukine GM-CSF ; Drug: Standard of care; Standard of care for COVID-19
Active Comparator: Control Arm Standard of care for COVID-19	Drug: Standard of care; Standard of care for COVID-19

Outcome Measures

Primary Outcome Measures

1. Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6 [1-6 days]

   The P(A-a)O2 gradient is a measure of how well the oxygen moves from the lungs into the bloodstream. Patients with a high gradient have less oxygen in the bloodstream.

2. Number of Patients Who Have Been Intubated by Day 14 [1-14 days]

Secondary Outcome Measures

1. Change in Ordinal Scale [1-28 days]

   The ordinal scale was used, where 0 is not hospitalized, no clinical or virological evidence of infection, and 8 is death.

2. All Cause 28-day Mortality [1-28 days]

3. Number of Patients With Treatment-related Adverse Events [1-58 days]

   Number of patients with side effects related to treatment with sargramostim. Patients on the control arm did not receive sargramostim.

4. Survival Time of Patients [Day 1-90]

5. Causes of Death [Day 1-90]

6. Change From Baseline in P/F Ratio [From Day 1 up to Day 6]

   The P/F ratio is a simple way to assess severity of low blood oxygen. It's the ratio of PaO2 (arterial oxygen partial pressure obtained from an arterial blood gas) to FiO2 (fraction of inspired oxygen expressed as a decimal). A normal arterial blood is gas 80 to 100 mm Hg. Normal room air has 21% or 0.21 oxygen. So a "normal" P/F ratio is about 380-475. A high P/F ratio means more oxygen in the bloodstream and a low P/F ratio means less oxygen in the bloodstream. This outcome measure compares the improvement (increase) in P/F ratio between treatment arms.

7. Number of Participants Wtih Nosocomial Infections [Day 1-90]

   Nosocomial infections also referred to as healthcare-associated infections (HAI), are infection(s) acquired during the process of receiving health care that was not present during the time of admission.

8. Number of Patients Requiring Invasive Mechanical Ventilation [Day 1-90]

   The is the number of patients that needed to be placed on a ventilator.

9. Duration of Invasive, Non-invasive and Supplemental Oxygen [Day 1-90]

   This endpoint includes duration of any/all types of respiratory support

10. Duration of Hospitalization [Day 1-90]

11. Time to Normalization of White Blood Cells and Lymphocytes [Day 1-90]

    Normalization of WBC and lymphocyte count is defined as whether WBC and lymphocyte count results are normal or below normal or above normal ranges at available visits.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients aged ≥ 18 years

• Patients (or legally authorized decision maker) must provide informed consent

• Test positive for SARS-CoV-2 virus by PCR

• Admitted to hospital

• Presence of acute hypoxemia defined as (either or both)

• saturation below 93% on ≥ 2 L/min oxygen supplementation

• PaO2/FiO2 below 350

Exclusion Criteria:

• Patients requiring invasive (mechanical ventilation) or non-invasive (CPAP, BiPAP for hypoxemia) ventilation or ECMO (Note: oxygen supplementation using high flow oxygen systems or low flow oxygen systems would not exclude patients from this study)

• Intractable metabolic acidosis

• Cardiogenic pulmonary edema

• Hypotension requiring use of vasopressors

• Hyperferritinemia (serum ferritin ≥2,000 mcg/L)

• White blood cell count > 50,000/mm3

• Participation in another interventional clinical trial for COVID-19 therapy

• Highly immunosuppressive therapy or anti-cancer combination chemotherapy within 24 hours prior to first dose of sargramostim

• Known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product

• Previous experience of severe and unexplained side effects during aerosol delivery of any kind of medical product

• Presence of any preexisting illness that, in the opinion of the Investigator, would place the patient at an unreasonably increased risk through participation in this study

• Pregnant or breastfeeding females

• Severe or uncontrolled pulmonary comorbid conditions, including systemic steroid dependent asthma, systemic steroid dependent COPD, oxygen dependent COPD, lung transplant, known interstitial lung disease, or cystic fibrosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Medical Center	Fullerton	California	United States	92835
2	St. Joseph Hospital of Orange	Orange	California	United States	92868
3	California Pacific Medical Center - Van Ness Campus	San Francisco	California	United States	94109
4	TidalHealth Peninsula Regional, Inc	Salisbury	Maryland	United States	21801
5	University of Missouri Health Care	Columbia	Missouri	United States	65212
6	Great Plains Health	North Platte	Nebraska	United States	69101
7	Richmond University Medical Center	Staten Island	New York	United States	10310
8	Brody School of Medicine at East Carolina University	Greenville	North Carolina	United States	27834
9	University of Toledo Medical Center	Toledo	Ohio	United States	43614
10	Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School	Houston	Texas	United States	77030
11	University of Utah Health	Salt Lake City	Utah	United States	84108

Sponsors and Collaborators

• Partner Therapeutics, Inc.
• United States Department of Defense

Investigators

• Study Director: Medical Information, Partner Therapeutics, Inc.

Study Documents (Full-Text)

• Study Protocol - Dec 2, 2020
• Statistical Analysis Plan - Mar 17, 2021

More Information

Publications

None provided.

• Responsible Party: Partner Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04411680
• Other Study ID Numbers: PTX-001-002
• First Posted: Jun 2, 2020
• Last Update Posted: Feb 18, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Partner Therapeutics, Inc.: COVID-19; sargramostim; Leukine; rhu-GM-CSF; acute hypoxemia; iLeukPulm; SARS-CoV-2
• Additional relevant MeSH terms: COVID-19; Sargramostim

Study Results

Participant Flow

Pre-assignment Detail	One participant was randomized to the sargramostim arm and then withdrew consent prior to treatment.

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Period Title: Treatment Period
STARTED	78	44
COMPLETED	49	36
NOT COMPLETED	29	8
Period Title: Treatment Period
STARTED	78	44
COMPLETED	60	30
NOT COMPLETED	18	14

Baseline Characteristics

Arm/Group Title	Sargramostim Arm	Control Arm	Total
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19	Total of all reporting groups
Overall Participants	78	44	122
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	47 60.3%	30 68.2%	77 63.1%
>=65 years	31 39.7%	14 31.8%	45 36.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.7 (13.00)	58.2 (10.61)	60.4 (12.26)
Sex: Female, Male (Count of Participants)
Female	43 55.1%	18 40.9%	61 50%
Male	35 44.9%	26 59.1%	61 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 30.8%	11 25%	35 28.7%
Not Hispanic or Latino	53 67.9%	33 75%	86 70.5%
Unknown or Not Reported	1 1.3%	0 0%	1 0.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 2.6%	0 0%	2 1.6%
Asian	2 2.6%	0 0%	2 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 2.3%	1 0.8%
Black or African American	6 7.7%	1 2.3%	7 5.7%
White	48 61.5%	33 75%	81 66.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	20 25.6%	9 20.5%	29 23.8%
Body Mass Index (kilograms/meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms/meter squared]	34.86 (8.988)	35.44 (9.647)	35.07 (9.200)

Outcome Measures

1. Primary Outcome

Title	Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6
Description	The P(A-a)O2 gradient is a measure of how well the oxygen moves from the lungs into the bloodstream. Patients with a high gradient have less oxygen in the bloodstream.
Time Frame	1-6 days

Outcome Measure Data

Analysis Population Description

Patients analyzed if they had both a baseline and at least 1 post-baseline measurement.

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	63	33
Least Squares Mean (Standard Error) [millimeters of mercury (mmHg)]	-102.3 (19.44)	-30.5 (26.88)

2. Primary Outcome

Title	Number of Patients Who Have Been Intubated by Day 14
Time Frame	1-14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Count of Participants [Participants]	9 11.5%	7 15.9%

3. Secondary Outcome

Title	Change in Ordinal Scale
Description	The ordinal scale was used, where 0 is not hospitalized, no clinical or virological evidence of infection, and 8 is death.
Time Frame	1-28 days

Outcome Measure Data

Analysis Population Description

Only 86 patients had follow up data at Day 28

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	61	25
Mean (Standard Deviation) [score on a scale]	-2.6 (1.49)	-2.5 (1.48)

4. Secondary Outcome

Title	All Cause 28-day Mortality
Time Frame	1-28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Count of Participants [Participants]	9 11.5%	6 13.6%

5. Secondary Outcome

Title	Number of Patients With Treatment-related Adverse Events
Description	Number of patients with side effects related to treatment with sargramostim. Patients on the control arm did not receive sargramostim.
Time Frame	1-58 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Count of Participants [Participants]	5 6.4%	0 0%

6. Secondary Outcome

Title	Survival Time of Patients
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Mean (Standard Deviation) [Days]	76.0 (27.05)	72.6 (28.56)

7. Secondary Outcome

Title	Causes of Death
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

Patients alive at Day 90 were not analyzed

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	11	8
Acute respiratory distress syndrome	4 5.1%	2 4.5%
Respiratory failure	6 7.7%	3 6.8%
Cardiorespiratory arrest	1 1.3%	2 4.5%
Septic shock	0 0%	1 2.3%

8. Secondary Outcome

Title	Change From Baseline in P/F Ratio
Description	The P/F ratio is a simple way to assess severity of low blood oxygen. It's the ratio of PaO2 (arterial oxygen partial pressure obtained from an arterial blood gas) to FiO2 (fraction of inspired oxygen expressed as a decimal). A normal arterial blood is gas 80 to 100 mm Hg. Normal room air has 21% or 0.21 oxygen. So a "normal" P/F ratio is about 380-475. A high P/F ratio means more oxygen in the bloodstream and a low P/F ratio means less oxygen in the bloodstream. This outcome measure compares the improvement (increase) in P/F ratio between treatment arms.
Time Frame	From Day 1 up to Day 6

Outcome Measure Data

Analysis Population Description

Patients were analyzed if they had both a baseline and at least 1 post-baseline measurement of P/F ratio.

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	63	33
Mean (Standard Deviation) [ratio]	65.70 (97.964)	47.24 (99.942)

9. Secondary Outcome

Title	Number of Participants Wtih Nosocomial Infections
Description	Nosocomial infections also referred to as healthcare-associated infections (HAI), are infection(s) acquired during the process of receiving health care that was not present during the time of admission.
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Count of Participants [Participants]	0 0%	0 0%

10. Secondary Outcome

Title	Number of Patients Requiring Invasive Mechanical Ventilation
Description	The is the number of patients that needed to be placed on a ventilator.
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Count of Participants [Participants]	12 15.4%	9 20.5%

11. Secondary Outcome

Title	Duration of Invasive, Non-invasive and Supplemental Oxygen
Description	This endpoint includes duration of any/all types of respiratory support
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Mean (Standard Deviation) [Days]	37.9 (35.64)	32.8 (34.25)

12. Secondary Outcome

Title	Duration of Hospitalization
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	78	44
Mean (Standard Deviation) [Days]	12.1 (9.39)	11.8 (8.63)

13. Secondary Outcome

Title	Time to Normalization of White Blood Cells and Lymphocytes
Description	Normalization of WBC and lymphocyte count is defined as whether WBC and lymphocyte count results are normal or below normal or above normal ranges at available visits.
Time Frame	Day 1-90

Outcome Measure Data

Analysis Population Description

Of 78 and 44 participants in the Sargramostim and Control Arms, respectively, only 28 (35.8%) and 17 (38.6%) had both baseline and post-baseline values available for evaluation at the Day 6 timepoint of interest.

Arm/Group Title	Sargramostim Arm	Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19	Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
Measure Participants	28	17
Mean (Standard Deviation) [Days]	NA (NA)	NA (NA)

Adverse Events

Time Frame	Adverse Events: Day 1-58, All-Cause Mortality: Day 1-90
Arm/Group Title	Sargramostim Arm		Control Arm
Arm/Group Description	Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period. Standard of care: Standard of care for COVID-19		Standard of care for COVID-19 Standard of care: Standard of care for COVID-19
All Cause Mortality
	Sargramostim Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/78 (14.1%)		8/44 (18.2%)
Serious Adverse Events
	Sargramostim Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/78 (19.2%)		14/44 (31.8%)
Cardiac disorders
Atrial fibrillation	1/78 (1.3%)		1/44 (2.3%)
Atrial flutter	0/78 (0%)		1/44 (2.3%)
Cardio-respiratory arrest	1/78 (1.3%)		1/44 (2.3%)
General disorders
Cardiac death	0/78 (0%)		1/44 (2.3%)
Infections and infestations
Cellulitis	1/78 (1.3%)		0/44 (0%)
Septic shock	0/78 (0%)		2/44 (4.5%)
Investigations
False positive investigation result	1/78 (1.3%)		0/44 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	1/78 (1.3%)		1/44 (2.3%)
Psychiatric disorders
Alcohol withdrawal syndrome	0/78 (0%)		1/44 (2.3%)
Renal and urinary disorders
Acute kidney injury	1/78 (1.3%)		2/44 (4.5%)
Anuria	0/78 (0%)		1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	4/78 (5.1%)		3/44 (6.8%)
Chronic obstructive pulmonary disease	1/78 (1.3%)		0/44 (0%)
Hypoxia	0/78 (0%)		1/44 (2.3%)
Pulmonary embolism	0/78 (0%)		2/44 (4.5%)
Respiratory failure	8/78 (10.3%)		5/44 (11.4%)
Other (Not Including Serious) Adverse Events
	Sargramostim Arm		Control Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/78 (60.3%)		30/44 (68.2%)
Blood and lymphatic system disorders
Anemia	5/78 (6.4%)		3/44 (6.8%)
Gastrointestinal disorders
Constipation	7/78 (9%)		3/44 (6.8%)
Infections and infestations
Septic shock	5/78 (6.4%)		1/44 (2.3%)
Metabolism and nutrition disorders
Hyperglycemia	8/78 (10.3%)		4/44 (9.1%)
Hypokalaemia	7/78 (9%)		3/44 (6.8%)
Psychiatric disorders
Anxiety	4/78 (5.1%)		4/44 (9.1%)
Insomnia	3/78 (3.8%)		4/44 (9.1%)
Renal and urinary disorders
Acute kidney injury	3/78 (3.8%)		4/44 (9.1%)
Vascular disorders
Hypotension	5/78 (6.4%)		4/44 (9.1%)

Limitations/Caveats

Limitations include lack of a blinded placebo control and reliance on ABG measurement for estimation of P(A-a)O2 gradient. Some clinical endpoints trial might have been affected by observer bias, availability of hospital or ICU resources, and/or hospital discharge. Missing ABG measurements may have resulted from decreased standard utilization of ABG in recent years, and hospital staff overload due to the COVID-19 pandemic may have led to absent follow-up assessment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.