Therapeutic Plasma Exchange Alone or in Combination With Ruxolitinib in COVID-19 Associated CRS

November 30, 2021 updated by: Prisma Health-Upstate

Interventional Study to Evaluate the Efficacy of Therapeutic Plasma Exchange (TPE) Alone or in Combination With Ruxolitinib in COVID-19 Positive Patients With PENN Grade 2, 3, 4 Cytokine Released Syndrome (CRS)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A virally mediated pandemic of 2020 is linked to a novel Beta Coronavirus (COVID-19) sharing subgenus classification with the severe acute respiratory syndrome (SARS) virus. The predominant modes of transmission are respiratory aerosolization and contaminated surface contact. COVID-19 infection is characterized by a wide range of severity and disease manifestations from asymptomatic to respiratory and multi organ failure. Definitive treatment is lacking, but there is an increasing awareness of its associated systemic cascade of inflammatory molecules that offers avenues to explore therapeutically.

Therapeutic plasma exchange (TPE) offers an immediate and scientifically grounded intervention for the removal of a host of pathogenic antibodies and toxic molecules by centrifugal separation of plasma or plasma membrane filtration. TPE in conjunction with Tocilizumab and steroids has been used successfully in the management of severe cytokine release syndrome (CRS) following chimeric antigen receptor T-cell therapy (CAR-T).

Precedence for consideration of TPE in a variety of inflammatory dominant disease states is also well known. Interest in adjuvant treatment for management of sepsis and multi organ dysfunction has been studied. TPE has also been used in three pediatric patients with pH1N1 influenza A acute respiratory failure and hemodynamic shock despite failure of best supportive care. All three survived with "good functional recovery."

Ruxolitinib is a Janus kinase (JAK) and signal transducer and activator of transcription (STAT) (JAK/STAT) pathway inhibitor which is FDA approved for polycythemia rubra vera, myelofibrosis and graft versus host disease. A murine model of CRS following CAR-T cellular therapy has been developed showing marked elevation of interleukin-6 (IL-6), interferon-gamma, tumor necrosis factor (TNF) alpha mimicking human CAR-T therapy induced CRS. Ruxolitinib treated mice demonstrated clinical amelioration and decrement in inflammatory cytokines. Incyte Corporation has announced plans to launch a Phase III trial of single agent ruxolitinib for COVID-19 associated cytokine storm.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Prisma Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 - TPE Alone
TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or fresh frozen plasma (FFP) replacement if underlying coagulopathy
Procedure: Therapeutic Plasma Exchange
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
Experimental: 2 - TPE Plus Ruxolitinib
TPE, five single plasma volume exchanges over 7 days (every day x 2 then every other day x 3) with albumin or fresh frozen plasma (FFP) replacement if underlying coagulopathy combined with ruxolitinib 5mg po twice daily (BID) beginning day prior to first TPE and continuing BID for total of 14 days.
Procedure: Therapeutic Plasma Exchange
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
Drug: Ruxolitinib
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.
Other Names:
  • Therapeutic Plasma Exchange

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
C-reactive Protein (CRP) Levels at Baseline and Day 14
Time Frame: Baseline and at Day 14
Defined as decreasing the CRP level from baseline to study day 14
Baseline and at Day 14
Cytokine Levels at Baseline and Day 14
Time Frame: Baseline and at Day 14
Defined as decreasing the interleukin (IL) IL-6 and IL-10 load and the tumor necrosis factor (TNF) load from baseline to study day 14
Baseline and at Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prisma Health-Upstate

Investigators

  • Principal Investigator: W. Larry Gluck, MD, Prisma Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2020

Primary Completion (Actual)

September 30, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

April 20, 2020

First Submitted That Met QC Criteria

May 2, 2020

First Posted (Actual)

May 5, 2020

Study Record Updates

Last Update Posted (Actual)

December 2, 2021

Last Update Submitted That Met QC Criteria

November 30, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHU COVID-19-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All individual participant date (IPD) that underlie results in a publication.

IPD Sharing Time Frame

Available April 2021 through December 2021

IPD Sharing Access Criteria

Data can be requested from the Principal Investigator via email and should include a description of the request and the associated project or use of the data.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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