NCT04326920: SARPAC

Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC)

Completed Phase 4 Results posted Last updated 16 November 2022

What this trial tests

Phase 4 trial testing Sargramostim in COVID-19 in 87 participants. Completed in 26 February 2021.

Timeline

24 March 2020

Primary endpoint
28 September 2020

26 February 2021

Quick facts

Lead sponsor	University Hospital, Ghent
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	87
Start date	24 March 2020
Primary completion	28 September 2020
Estimated completion	26 February 2021
Sites	4 locations across Belgium

Drugs / interventions tested

• Sargramostim (SARGRAMOSTIM) — full drug profile →
• Control

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

University Hospital, Ghent

Who can join

Adults 18 to 80, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Improvement in Oxygenation Primary · on Day 6 or hospital discharge, whichever came first

Mean Change from Baseline in PaO2/FiO2 on Day 6 or hospital discharge, whichever came first

Group	Value	95% CI
Active Sargramostim Treatment Group	25.7	± 85.3
Control Group	29.7	± 71.88

Mean Change in 6-point Ordinal Scale for Clinical Improvement Secondary · at Baseline, at Day 6

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

Group	Value	95% CI
Active Sargramostim Treatment Group	0.3	± 1.0
Control Group	0.3	± 1.0

Number of Days in Hospital Secondary · through study completion, an average of 5 months

Group	Value	95% CI
Active Sargramostim Treatment Group	8.5	6 – 12
Control Group	9.0	7 – 14

Number of Participants With Nosocomial Infection no./Total no (%) Secondary · during hospital admission (up to 28 days)

Group	Value	95% CI
Active Sargramostim Treatment Group	2
Control Group	1

Death Secondary · at 28 days

Group	Value	95% CI
Active Sargramostim Treatment Group	2
Control Group	2

Number of Participants Progressed to Mechanical Ventilation and/or ARDS Secondary · during hospital admission (up to 28 days)

Group	Value	95% CI
Active Sargramostim Treatment Group	7
Control Group	6

Time to Clinical Sign Score < 6 for at Least 24h Secondary · 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

Group	Value	95% CI
Active Sargramostim Treatment Group	2.0	1.0 – 3.0
Control Group	3.0	1.0 – 6.0

Change in Clinical Sign Score Secondary · at baseline, at day 6

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.

Group	Value	95% CI
Active Sargramostim Treatment Group	-2.0	± 3.1
Control Group	-2.2	± 3.0

Change in (National Early Warning Score2) NEWS2 Score Secondary · at baseline, at day 6

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

Group	Value	95% CI
Active Sargramostim Treatment Group	-0.6	± 3.1
Control Group	-0.4	± 3.0

Change in Sequential Organ Failure Assessment (SOFA Score) Secondary · at baseline, at day 6

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.

Group	Value	95% CI
Active Sargramostim Treatment Group	-0.5	± 1.5
Control Group	-0.4	± 1.2

Change in Ferritin Level Secondary · at baseline, at day 6

Group	Value	95% CI
Active Sargramostim Treatment Group	-90	-150 – 34
Control Group	-112	-259 – 118

Change in D-dimer Level Secondary · at baseline, at day 6

Group	Value	95% CI
Active Sargramostim Treatment Group	-0.71	-1.79 – 1.33
Control Group	-0.44	-2.90 – 2.46

Adverse events — posted to ClinicalTrials.gov

Time frame: Timeframe for reporting adverse events: through study completion, an average of 5 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active Sargramostim Treatment Group

Serious: 6/40 (15%)

Deaths: 4/40

Control Group

Serious: 6/41 (15%)

Deaths: 8/41

Serious adverse events (13 terms)

Reaction	System	Active Sargramostim Treatm…	Control Group
Thormboembolic event	Vascular disorders	—	—
Respiratory distress	Respiratory, thoracic and mediastinal disorders	—	—
Ventilator associated pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Aspergillus infection	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory deterioration due to underlying MPO-ANCA vasculitis and aspergillosis	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Presyncope	Nervous system disorders	—	—
Persistent catatonic state and neurological deficits	Psychiatric disorders	—	—
Invasive aspergillosis	Infections and infestations	—	—
Multi-bacterial bacteremia causing hemorrhagic shock	Infections and infestations	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Active Sargramostim Treatm…	Control Group
Infectious disorder (not COVID-19)	Infections and infestations	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Cardiac disorder	Cardiac disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—

Most-reported serious reactions: Thormboembolic event, Respiratory distress, Ventilator associated pneumonia, Aspergillus infection, Respiratory deterioration due to underlying MPO-ANCA vasculitis and aspergillosis, Respiratory failure, Pneumonia, Hypoxia.

Data from ClinicalTrials.gov NCT04326920 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
   Merad M, Martin JC. · · 2020 · cited 1909× · PMID 32376901 · DOI 10.1038/s41577-020-0331-4
2. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions.
   Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, et al · · 2020 · cited 246× · PMID 32687918 · DOI 10.1016/j.lfs.2020.118102
3. Pharmaco-Immunomodulatory Therapy in COVID-19.
   Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, et al · · 2020 · cited 190× · PMID 32696108 · DOI 10.1007/s40265-020-01367-z
4. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
5. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches.
   Lang FM, Lee KM, Teijaro JR, Becher B, et al · · 2020 · cited 178× · PMID 32576980 · DOI 10.1038/s41577-020-0357-7
6. Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.
   Bonaventura A, Vecchié A, Wang TS, Lee E, et al · · 2020 · cited 112× · PMID 32719685 · DOI 10.3389/fimmu.2020.01625
7. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities.
   Mehta P, Porter JC, Manson JJ, Isaacs JD, et al · · 2020 · cited 105× · PMID 32559419 · DOI 10.1016/s2213-2600(20)30267-8
8. The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections.
   Hsu RJ, Yu WC, Peng GR, Ye CH, et al · · 2022 · cited 98× · PMID 35464491 · DOI 10.3389/fimmu.2022.832394