Therapeutic Plasma Exchange Alone or in Combination With Ruxolitinib in COVID-19 Associated CRS
Condition: Cytokine Release Syndrome; COVID19
MeSH terms: COVID-19; Syndrome; Cytokine Release Syndrome
Intervention: Therapeutic Plasma Exchange; Ruxolitinib
Intervention description: TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or FFP replacement if underlying coagulopathy; TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or FFP replacement if underlying coagulopathy combined with ruxolitinib 5mg po BID beginning day prior to first TPE and continuing BID for total of 14 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 12 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      This protocol will evaluate the efficacy of Therapeutic Plasma Exchange (TPE) alone or in
      combination with ruxolitinib in COVID positive patients with PENN grade 2, 3, 4 cytokine
      release syndrome (CRS). It is hypothesized that dual intervention of acute apheretic
      depletion of cytokines and concomitant suppression of production will produce superior
      amelioration of the cytokine load and to help to prevent cytokine load rebound. This protocol
      is envisioned as a pilot study (n=20) for hypothesis generation for future investigation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients positive for COVID-19 by polymerase chain reaction (PCR) assay or alternative
             accepted methodology

          2. PENN class 2,3,4 CRS

          3. Respiratory insufficiency with supplemental oxygen to maintain O2 sat greater than 89%

          4. Clinically positive imaging by chest x-ray (CXR) or CT scan with evidence of bilateral
             pulmonary infiltrates, ground glass opacification or other pattern of consolidation
             felt likely to be linked to COVID infection or complication thereof

          5. Age 12-80 years of age

        Exclusion Criteria:

          1. Pregnancy

          2. Breast feeding

          3. Class 3-4 New York Heart Association (NYHA) heart failure

          4. Current use of synthetic disease modifying anti-rheumatic drugs (DMARDS) or IL-6
             inhibitors or other immunosuppressive therapies outside of number five below

          5. Current use of chronic corticosteroids if in excess of prednisone 10mg per day or
             equivalent

          6. Suspected or confirmed clinically significant bacterial infection

          7. History of tuberculosis (TB)

          8. History of HIV

          9. History of irritable bowel disease (IBD)

         10. JAK inhibitor use within last 30 days

         11. Creatinine clearance less than 15 ml / min

         12. Absolute neutrophil count < 1000

         13. Platelet count < 50,000

         14. Clinical assessment that the trial could pose unacceptable risk by study participation

         15. Current enrollment on another investigational protocol for COVID-19 induced CRS

         16. Stage 4 obstructive lung disease with chronic hypoxic respiratory failure requiring
             supplemental O2 at baseline, or interstitial lung disease (ILD) with chronic hypoxic
             respiratory failure requiring supplemental O2 at baseline