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

NCT04326920 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: SARPAC
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

COVID-19

Keywords

GM-CSF; Acute Lung Injury; Hypoxia; Acute Respiratory Distress Syndrome; Corona virus; COVID-19; SARS (Severe Acute Respiratory Syndrome); Alveolar Macrophage; Acute Hypoxic respiratory failure

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (15)

• Mean Change in 6-point Ordinal Scale for Clinical Improvement

  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)

Study Arms (2)

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

Drug: Sargramostim

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

Drug: Sargramostim; Other: Control

Interventions

Sargramostim DRUG

Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration

Also known as: LEUKINE

Active sargramostim treatment group; Control group

Control OTHER

Standard of care

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• saturation below 93% on minimal 2 l/min O2
• PaO2/FiO2 below 300
• Admitted to specialized COVID-19 ward
• Age 18-80
• Male or Female
• Willing to provide informed consent

You may not qualify if:

• Patients with known history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony stimulating factor such as sargramostim, yeast-derived products, or any component of the product.
• mechanical ventilation before start of study
• patients with peripheral white blood cell count above 25.000 per microliter and/or active myeloid malignancy
• patients on high dose systemic steroids (\> 20 mg methylprednisolone or equivalent)
• patients on lithium carbonate therapy
• Patients enrolled in another investigational drug study
• Pregnant or breastfeeding females (all female subjects regardless of childbearing potential status must have negative pregnancy test at screening)
• Patients with serum ferritin \>2000 mcg/ml (which will exclude ongoing HLH)

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Flemish institute of biotechnology (VIB): collaborator

Study Sites (4)

AZ Sint Jan Brugge

Bruges, 8000, Belgium

Location

University Hospital Ghent

Ghent, 9000, Belgium

Location

UZ Brussel

Jette, 1090, Belgium

Location

AZ Delta Roeselare

Roeselare, 8800, Belgium

Location

Related Publications (3)

• 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.

  PMID: 36459994 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.

  PMID: 32559419 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.

  PMID: 32503663 DERIVED

MeSH Terms

Conditions

COVID-19; Acute Lung Injury; Hypoxia; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome

Interventions

sargramostim

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Results Point of Contact

• Title: Cedric Bosteels
• Organization: UZ Gent

cedric.bosteels@ugent.be

+3293325909

Study Officials

• Bart Lambrecht

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, VIB-UGent Center for Inflammation Research

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 30, 2020
• Study Start: March 24, 2020
• Primary Completion: September 28, 2020
• Study Completion: February 26, 2021
• Last Updated: November 16, 2022
• Results First Posted: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)