REVERSE-LC is a phase 3 trial of baricitinib versus placebo in adults with neurocognitive impairment (a form of Alzheimer's Disease and Related Dementias or ADRD) or cardiopulmonary symptoms due to Long COVID.
This is a multi-site randomized, placebo-controlled, double-blind, parallel-design REVERSE-LC phase 3 study. Individuals meeting inclusion criteria will be randomized to one of two arms: the intervention arm of baricitinib 4 mg daily for 24 weeks (dose adjusted to 2 mg or 1 mg for baseline renal dysfunction) versus the placebo arm for 24 weeks. In addition to safety, a variety of clinical and biological outcome measures will be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Nonproprietary name: Baricitinib
Placebo
University of California San Francisco
San Francisco, California, United States
Yale University
New Haven, Connecticut, United States
Emory University
Atlanta, Georgia, United States
University of Minnesota
Minneapolis, Minnesota, United States
Enrollment
2 participants per month, on average, are randomized
Time frame: 6 months
Diversity in enrollment
40% of participants will be from individuals disproportionally affected by COVID (Black, Hispanic, Asian, American Indian)
Time frame: 6 months
Study drug prescribed
80% of participants received every prescribed dose of the study drug
Time frame: 9 months
Study withdrawals
Less than 20% participants will be deemed lost to follow up
Time frame: 18 months
Adverse event reporting
100% of Serious Adverse Events reported to Data Safety Monitoring Board within 24 hours of study team awareness
Time frame: 18 months
Study dosing
100% adherence to study drug dose adjustments guidelines
Time frame: 9 months
Study completion
80% of participants adhere to all study procedures and requirements
Time frame: 18 months
Severe and Serious Adverse Events
Compare the percentage of severe and serious adverse events between study arms from baseline to week 12.
Time frame: 9 months
Premature study discontinuation
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Vanderbilt University
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Compare the rate of study drug/placebo premature discontinuation by study arm (tolerability)
Time frame: 9 months
Global Neuropsychological Function
Assess percentage changes of global neuropsychological function as measured using the CNS Vital Signs Neurocognition Index cognitive battery between baricitinib and placebo study arm from baseline to week 12.
Time frame: 9 months
Cardiopulmonary testing
Assess percentage changes of exercise capacity (peak VO2) using cardiopulmonary exercise testing (CPET) in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Everyday Cognition
Assess percentage changes of cognitive impairment using Everyday Cognition (ECog) scale in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Functional Status
Assess percentage changes of functional status measures in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Quality of Life Measures
Assess percentage changes of quality of life measures in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Post-Exertional Malaise
Assess percentage changes of post-exertional malaise using De Paul Symptom Questionnaire - Post-Exertional Malaise (DSQ-PEM) in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Shortness of Breath
Assess percentage changes of the effect of breathlessness on daily activities using the Modified Medical Research Council Dyspnea Scale (mMRC) in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Symptom Burden
Assess percentage changes of post COVID-19 symptom burden using the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale in the baricitinib arm compared to the placebo arm from baseline to week 12
Time frame: 9 months
Inflammation biomarkers
Decreases in plasma biomarkers of inflammation in the baricitinib arm compared to placebo arm from baseline to week 12
Time frame: 9 months
Viral Reservoirs
Decreases in viral reservoirs for the baricitinib arm compared to placebo arm from baseline to week 12
Time frame: 9 months