COVID-19
Conditions
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.
Interventions
DRUGRuxolitinib
For patients unable to swallow pills, a ruxolitinib suspension will be administered through a nasogastric/orogastric tube
PROCEDUREPeripheral blood draw
-Screening, Day 2, Day 4, Day 8, Day 15, and Day 29
Sponsors
Incyte Corporation
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | Through 28 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of ICU stay | Through completion of follow-up (estimated to be 7 months) | — |
| Duration of ventilator use | Through completion of follow-up (estimated to be 7 months) | — |
| Duration of vasopressors use | Through completion of follow-up (estimated to be 7 months) | — |
| Length of hospital stay | Through completion of follow-up (estimated to be 7 months) | — |
| Viral kinetics as measured by virologic failure | Through completion of follow-up (estimated to be 7 months) | -Defined as increase in viral load of \>0.5 log on two consecutive days, or \>1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing |
| Number of adverse events as measured by CTCAE v. 5.0 | Through completion of follow-up (estimated to be 7 months) | — |
| Proportion of participants with detectable virus | Day 5 | — |
| Duration on renal replacement therapy | Through completion of follow-up (estimated to be 7 months) | — |
Outcome results
None listed