Study of Sargramostim in Patients With COVID-19
- Registration Number
- NCT04411680
- Lead Sponsor
- Partner Therapeutics, Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 123
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sargramostim Arm Standard of care Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Control Arm Standard of care Standard of care for COVID-19 Sargramostim Arm Sargramostim Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19
- Primary Outcome Measures
Name Time Method Number of Patients Who Have Been Intubated by Day 14 1-14 days 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.
- Secondary Outcome Measures
Name Time Method Survival Time of Patients Day 1-90 All Cause 28-day Mortality 1-28 days 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.
Causes of Death Day 1-90 Number of Patients Requiring Invasive Mechanical Ventilation Day 1-90 The is the number of patients that needed to be placed on a ventilator.
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.
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.
Duration of Hospitalization Day 1-90 Duration of Invasive, Non-invasive and Supplemental Oxygen Day 1-90 This endpoint includes duration of any/all types of respiratory support
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.
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.
Trial Locations
- Locations (11)
Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School
🇺🇸Houston, Texas, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
St. Jude Medical Center
🇺🇸Fullerton, California, United States
University of Missouri Health Care
🇺🇸Columbia, Missouri, United States
California Pacific Medical Center - Van Ness Campus
🇺🇸San Francisco, California, United States
St. Joseph Hospital of Orange
🇺🇸Orange, California, United States
TidalHealth Peninsula Regional, Inc
🇺🇸Salisbury, Maryland, United States
Great Plains Health
🇺🇸North Platte, Nebraska, United States
Richmond University Medical Center
🇺🇸Staten Island, New York, United States
Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States