Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID
REVERSE-LC
2 other identifiers
interventional
550
1 country
16
Brief Summary
The overarching goal of this study is to determine if baricitinib, as compared to placebo, will improve neurocognitive function, along with measures of physical function, quality of life, post-exertional malaise, effect of breathlessness on daily activities, post-COVID-19 symptom burden, and biomarkers of inflammation and viral measures, in participants with Long COVID.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2024
Typical duration for phase_3
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 4, 2024
CompletedFirst Posted
Study publicly available on registry
October 8, 2024
CompletedStudy Start
First participant enrolled
October 21, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
April 22, 2026
April 1, 2026
2 years
October 4, 2024
April 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
CNS-Vital Signs Global Cognitive Index
Objective neuropsychological function determined using the CNS-Vital Signs Global Cognitive Index between study arms at 6-months, adjusted for baseline. CNS-Vital Signs Global Cognitive Index subscale is an average score derived from the domain scores or a general assessment of the overall neurocognitive status of the participant. The scores range from less than 70 (very low) to above 110 (above average). A higher score means higher neurocognitive function and higher capacity.
Month 6
Secondary Outcomes (14)
Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 6-months.
Month 6
Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 12-months.
Month 12
Modified Everyday Cognition (mECog)
Months 3, 6 and 12
Exercise capacity including the 6-minute walk test (6MWT) at 6- and 12-months
Months 6 and 12
Cardiopulmonary exercise testing (CPET)
Months 6 and 12
- +9 more secondary outcomes
Study Arms (2)
Baricitinib
EXPERIMENTALJanus kinase inhibitor
Placebo
PLACEBO COMPARATORPlacebo
Interventions
4mg encapsulated, pre-formed tablet PO once daily for 24 weeks.
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this investigation, an individual must meet all of the following criteria:
- Cohort #1 (n=500):
- Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation.
- Age ≥18 years old.
- Documented SARS-CoV-2 infection 6 or more months prior to screening, confirmed with acceptable documentation that includes (at minimum) their name, the date the test was taken (must be after January 2020), and details specifying that the positive test was for SARS-CoV-2 infection.
- Clinical evidence of Long COVID, as confirmed by the investigator's assessment:
- a. At least one symptom (listed below) that is new or worsened since the time of SARS-CoV-2 infection, not known to be attributable to another cause upon assessment by the study clinicians (MD, DO, NP, PA, RN, or equivalent).
- i. Systemic symptoms (e.g., fatigue, chills, post-exertional malaise), neurocognitive symptoms (e.g., trouble with memory/concentration ("brain fog"), headache, dysautonomia/postural orthostatic tachycardia syndrome, dizziness, unsteadiness, neuropathy, sleep disturbance), cardiopulmonary symptoms (e.g., chest pain, palpitations, shortness of breath, cough, fainting spells), musculoskeletal symptoms (e.g., muscle aches, joint pain), gastrointestinal symptoms (e.g., nausea, diarrhea). Although other symptoms (e.g., skin rash, hair loss, mental health symptoms, trouble with smell/taste, genitourinary symptoms) will be recorded and tracked, at least one core symptoms listed above must be present.
- b. Symptoms must be present for at least 6 months prior to screening. Symptoms that wax and wane must have been initially present at least 6 months prior to screening.
- c. Symptoms must be reported to have an impact on quality of life and/or everyday functioning and to be at least somewhat bothersome.
- d. Cognitive impairment present defined by having at least 20% positive items (answered subjectively worse or much worse) on the 41-item modified ECog questionnaire.
- Cohort #2 (n=50):
- Evidence of personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study and was willing and able to consent to participation.
- Age ≥18 years old.
- Clinical diagnosis of COVID infection between January 2020 and September 1, 2021 (i.e., before home tests were widely available).
- +10 more criteria
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this investigation:
- Qualifying Long COVID symptoms cannot be explained by an infection-associated chronic condition diagnosed prior to the onset of Long COVID (e.g., ME/CFS or other infection-associated chronic condition).
- Pre-existing cognitive impairment not exacerbated by COVID-19, including but not limited to syphilis, as determined by study clinicians (MD, DO, NP, PA, RN, or equivalent), which may include a review of participant's history and medical records.
- Severe cognitive, physical, or psychological disability preventing participation in the study, as determined by the investigator.
- Moderate or High risk of suicidality, as determined by the modified Columbia Suicide Severity Rating Scale (mC-SSRS).
- History of a major adverse cardiovascular event (MACE) within the 3 months prior to enrollment.
- Known prior allergic reactions to components of the baricitinib.
- Previously randomized in this study or in the last 30 days have been in another study investigating baricitinib.
- Positive SARS-CoV-2 NAAT or rapid Antigen test in the 14 days prior to screening.
- Venous thromboembolism in the past 6 months prior to screening or felt to be at increased risk of thrombosis by the investigator.
- Previous admission to an ICU for treatment of acute COVID-19 infection.
- Estimated glomerular filtration rate of \< 30 mL/min/1.73m2, as calculated using the CKD-EPI 2021 equation.
- Absolute Neutrophil Count (ANC) \<1000 cells/mm3, confirmed on repeat testing.
- Absolute Leukocyte Count (ALC) \<100 cells/mm3.
- Evidence of severe liver disease at the time of screening, defined as Bilirubin \> 1.5 X ULN or AST or ALT \> 2x ULN.
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Wes Elylead
- National Institutes of Health (NIH)collaborator
- National Institute on Aging (NIA)collaborator
Study Sites (16)
University of Arizona
Tucson, Arizona, 85724, United States
University of California, Los Angeles (UCLA)
Los Angeles, California, 90024, United States
University of California San Francisco
San Francisco, California, 94143, United States
University of Colorado I Anschutz Medical Campus
Aurora, Colorado, 80045, United States
Yale University
New Haven, Connecticut, 06510, United States
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
Emory University
Atlanta, Georgia, 30322, United States
Illinois Research Network (ILLInet), University of Illinois Chicago
Chicago, Illinois, 60608, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University Hospitals Cleveland Case Western
Cleveland, Ohio, 44106, United States
The MetroHealth System
Cleveland, Ohio, 44109, United States
Vanderbilt University Medical
Nashville, Tennessee, 37203, United States
University of Texas at San Antonio
San Antonio, Texas, 78229, United States
Swedish Medical Center
Seattle, Washington, 98104, United States
West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia, 26506-7015, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Wes Ely, M.D.
Vanderbilt University Medical Center
Central Study Contacts
Wes Ely, M.D.
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor, Allergy, Pulmonary, and Critical Care Medicine
Study Record Dates
First Submitted
October 4, 2024
First Posted
October 8, 2024
Study Start
October 21, 2024
Primary Completion (Estimated)
November 1, 2026
Study Completion (Estimated)
July 1, 2027
Last Updated
April 22, 2026
Record last verified: 2026-04