Sargramostim in Patients With Acute Hypoxic Respiratory Failure Due to COVID-19 (SARPAC)
Condition: COVID-19
MeSH terms: COVID-19; Respiratory Insufficiency
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Leukine® is a yeast-derived recombinant humanized granulocyte-macrophage colony stimulating
      factor (rhuGM-CSF, sargramostim) and the only FDA approved GM-CSF. GMCSF, a pleiotropic
      cytokine, is an important leukocyte growth factor known to play a key role in hematopoiesis,
      effecting the growth and maturation of multiple cell lineages as well as the functional
      activities of these cells in antigen presentation and cell mediated immunity.

      Leukine inhalation or intravenous administration, as an adjuvant therapy, may confer benefit
      to patients with ARDS (Acute Respiratory Distress Syndrome) due to COVID-19 exposure, who are
      at significant risk of mortality. While there is no active IND (Investigational New Drug) for
      Leukine in the proposed patient population, Leukine is being studied in Fase II as an
      adjuvant therapy in the management of life-threatening infections to boost the hosts innate
      immune response to fight infection, reduce the risk of secondary infection, and in varied
      conditions as prevention of infection during critical illness. Inhaled Leukine has also been
      successfully used as primary therapy to improve oxygenation in patients with disordered gas
      exchange in the lungs. We propose that based on preclinical and clinical data, Leukine
      inhalation, as an adjuvant therapy, has an acceptable benefit-risk for use in patients with
      hypoxic respiratory failure and ARDS due to COVID-19 exposure, who are at significant risk of
      mortality.

      Confirmed COVID19 patients with hypoxic respiratory failure (saturation below 93% on minimal
      2 l/min O2) will be randomized to receive sargramostim 125mcg twice daily for 5 days as a
      nebulized inhalation on top of standard of care, or to receive standard of care treatment.
      Upon progression of disease requiring initiation of mechanical ventilatory support within the
      5 day period, in patients in the active group, inhaled sargramostim will be replaced by
      intravenous sargramostim 125mcg/m2 body surface area 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. In the
      control group progressive disease requiring mechanical ventilatory support, from day 6
      onwards, the treating physician will have the option to initiate IV sargramostim 125mcg/m2
      body surface area for 5 days. Safety data, including blood leukocyte counts, will be
      collected in all patients. Efficacy data will also be collected and will include arterial
      blood gases, oxygenation parameters, need for ventilation, lung compliance, organ function,
      radiographic changes, ferritin levels, etc. as well as occurrence of secondary bacterial
      infections.
    

Intervention name(s): Sargramostim; Control
Intervention type(s): Drug; Other
Intervention description(s): Inhalation via mesh nebulizer and/or IV administration upon Clinical deterioration; Standard of care
Other intervention name(s): LEUKINE
Intervention MeSH terms: Sargramostim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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