Covid-19 living Data

Sargramostim vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-09-04

Studies description

Trial NCT04326920
Publication Bosteels C, ResearchSquare (2021) (preprint)
Dates: 2020-03-25 to 2020-09-28
Funding: Mixed (Ghent University Hospital; Partner Therapeutics LLC (Lexington, MA) provided the study medication; The Ghent University Special Research Fund; VIB Grand Challenges program (Flanders Institute for Biotechnology); Chan Zuckerberg Initiative.)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / Belgium Follow-up duration (days): 140
Inclusion criteria	18-80 years of age confirmed recent COVID-19 pneumonia (i.e. positive polymerase-chain reaction (PCR) assay, antigen detection test or serology < 2 weeks prior to randomization) acute respiratory failure defined as a ratio of the partial arterial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) below 350 mmHg or blood oxygen saturation level (SpO2) below 93% on minimal 2 L/min supplemental oxygen.
Exclusion criteria	Known serious allergic reactions to yeast-derived products lithium carbonate therapy mechanical ventilation prior to randomization peripheral white blood cell count above 25.000/μL and/or active myeloid malignancy high dose systemic steroid therapy (> 20 mg methylprednisolone or equivalent) for a COVID-19-unrelated disorder enrolment in another investigational study pregnant or breastfeeding ferritin levels > 2000 μg/mL (which will exclude ongoing CRS).
Interventions
	Treatment Sargramostim 125 mcg nebulized inhalation twice a day for 5 days (if intubated replaced by 125 μg/m2 body surface area intravenously once daily )
	Control Standard care
Participants
	Randomized participants : Standard care=41 Sargramostim=40
	Characteristics of participants N= 81 Mean age : NR 51 males Severity : Mild: n=4 / Moderate: n=71 / Severe: n=6 Critical: n=0
Primary outcome
	In the register Improvement in oxygenation at a dose of 250 mcg daily during 5 days improves oxygenation in COVID-19 patients with acute hypoxic respiratory failure [ Time Frame: at end of 5 day treatment period ] by mean change in PaO2/FiO2 (PaO2=Partial pressure of oxygen; FiO2= Fraction of inspired oxygen)
	In the report Improvement in oxygenation after 5 days of sargramostim treatment and/or standard of care. Oxygenation was assessed by the PaO2/FiO2 ratio and P(Aa)O2 gradient.
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registry, published and full protocols, statistical analysis plan and supplementary appendices were used in data extraction and assessment of risk of bias. The primary outcome in the article reflected that in the registry. The study (n = 81) achieved its target sample size (n = 80). The study was updated on December 17th, 2021 with additional data from authors.

Trial NCT04411680
Publication iLeukPulm - NCT04411680, Unpublished (2022) (results posted on registry)

Funding: Mixed (Partner Therapeutics, Inc, Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense's (JPEO-CBRND) Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical (JPM CBRN Medical), under project agreement MCDC2006-012)
Conflict of interest: *

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA Follow-up duration (days): 90
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.
Interventions
	Treatment Sargramostim 125 mcg inhaled twice daily for 5 days or 125mcg/m2 intravenously every day for 5 days
	Control Standard care
Participants
	Randomized participants : Sargramostim=79 Standard care=44
	Characteristics of participants N= 123 Mean age : NR 61 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=44 Critical: n=0
Primary outcome
	In the register 1. Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6 [ Time Frame: 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 [ Time Frame: 1-14 days ]
	In the report NR
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	High
General comment	The trial registry, protocol and statistical analysis plane were used in data extraction and assessment of risk of bias. This is an unpublished study whose results have been reported in ClinicalTrials.gov. The trial was registered prospectively and no important changes were made to primary or secondary outcomes after recruitment start. The trial (n = 123) achieved its target sample size (n = 120). Trial data were updated on September 1st, 2022 with data extracted after contact with authors.