Clinical trial NCT04354714: Ruxolitinib to Combat COVID-19
Official title: A Pilot Study of Ruxolitinib to Combat COVID-19
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
First posted: 2020-04-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators hypothesize that JAK 1/2 inhibition with ruxolitinib, an FDA approved treatment for intermediate or high-risk myelofibrosis, could have a similar effect in patients with severe COVID-19, quelling the immune-hyperactivation, allowing for clearance of the virus and reversal of the disease manifestations.


Eligibility criteria: Inclusion Criteria:

* A diagnosis of advanced COVID-19 as defined by both of the following:

  * A positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), analyzed by a CLIA certified lab
  * Critical disease manifested by any of the following:

    * Chest imaging (CT or chest X-ray permitted) with ≥ 50% lung involvement
    * Respiratory failure requiring invasive mechanical ventilation or supplementary oxygen with FiO2 ≥ 50%
    * Shock (defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg isotonic intravenous fluid resuscitation and/or requiring vasopressor support
    * Cardiac dysfunction defined by:

      * New global systolic dysfunction with ejection fraction ≤ 40%
      * Takotsubo cardiomyopathy
      * New onset supraventricular or ventricular arrhythmias
      * Plasma troponin I ≥ 0.10 ng/mL in someone without previously documented troponin elevation beyond that level
      * Elevated plasma NT-proBNP in someone without documented prior elevation

        * If Age \< 50, NT-proBNP \> 450 pg/ml
        * If Age 50-74, NT-proBNP \> 900 pg/ml
        * If Age ≥ 74, NT-proBNP \> 1800 pg/ml
* Receipt of investigational or off-label agents for COVID-19 (prior or ongoing) does not exclude eligibility.
* Patients who have received autologous or allogeneic stem cell transplant are eligible at the discretion of the investigators.
* 18 years of age or older at the time of study registration
* Adequate hematologic function defined as:

  * absolute neutrophil count ≥ 1000/mm3
  * platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days prior to screening
* Creatinine clearance ≥ 15 mL/minute or receiving renal replacement therapy
* Women of childbearing potential (defined as women with regular menses, women with amenorrhea, women with irregular cycles, women using a contraceptive method that precludes withdrawal bleeding, or women who have had a tubal ligation) are required to have a negative pregnancy test and use two forms of acceptable contraception, including one barrier method, during participation in the study treatment period.
* Male patients (if engaging in reproductive sex with a women of childbearing potential) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the evaluation period.
* Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

* Known allergy or intolerance to ruxolitinib or another JAK inhibitor.
* Known or suspected active viral (including HIV, hepatitis B, and hepatitis C), bacterial, mycobacterial, or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
* Pregnant and/or breastfeeding.
* Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator.

Primary outcomes:
measure: Overall survival
timeFrame: Through 28 days
Secondary outcomes:
measure: Length of hospital stay
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Length of ICU stay
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Duration of ventilator use
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Duration of vasopressors use
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Duration on renal replacement therapy
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Viral kinetics as measured by virologic failure
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Number of adverse events as measured by CTCAE v. 5.0
timeFrame: Through completion of follow-up (estimated to be 7 months)
measure: Proportion of participants with detectable virus
timeFrame: Day 5
measure: Proportion of participants with detectable virus
timeFrame: Day 10
measure: Proportion of participants with detectable virus
timeFrame: Day 15
measure: Proportion of participants with detectable virus
timeFrame: Day 29
Other outcomes:
Locations:
Study officials:
affiliation: Washington University School of Medicine
name: John DiPersio, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: