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Long COVIDPhase 3REVERSE-LCNCT06631287

Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID

A Phase 3 study testing Baricitinib in people with Long COVID and Sars-CoV-2 Infection, run by Wes Ely at 17 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Baricitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
550 participants
Where
17 sitesUnited States
Study dates
21 Oct 2024to 1 Jul 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 25Show fewer
  • 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).
  • 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.
  • 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.
  • Symptoms must be reported to have an impact on quality of life and/or everyday functioning and to be at least somewhat bothersome.
  • 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).
  • Clinical Criteria (Based on Council of State and Territorial Epidemiologists Standardized Surveillance Case Definition for COVID-19): i. At least two of the following symptoms: Fever (measured or subjective), chills, rigors, myalgia, headache, sore throat, new olfactory and taste disorder(s).
  • -OR- ii. At least one of the following symptoms: Cough, shortness of breath, or difficulty breathing.
  • -OR- iii. Severe respiratory illness with at least one of the following: clinical or radiographic evidence of pneumonia or Acute Respiratory Distress Syndrome (ARDS).
  • -AND- iv. No alternate more likely diagnosis
  • Clinical evidence of Long COVID, as confirmed by the clinician's assessment:
  • 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).
  • 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.
  • 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.
  • Symptoms must be reported to have an impact on quality of life and/or everyday functioning and to be at least somewhat bothersome.
  • Cognitive impairment present defined by having at least 20% positive items (answered subjectively worse or much worse) on the 41-item modified ECog questionnaire.

Who cannot join

  • 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.
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  • Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs); however, DMARDs with minimal immunomodulatory effects (hydroxychloroquine, i.e., Plaquenil, steroids used for less than 2 weeks, minocycline), are not exclusionary.
  • 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.
  • Malignancy or lymphoproliferative disorder not in remission for at least 5 years. Local non-melanoma skin cancers that are definitively managed are not exclusionary.
  • 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.
  • Alkaline Phosphatase (ALP) ≥ 3x ULN.
  • Creatine Phosphokinase (CPK) ≥ 3x ULN.
  • Hemoglobin (HgB) < 8 g/dL, confirmed on repeat testing.
  • Platelets <100,000 cells/mm3, confirmed on repeat testing.
  • Platelets >500,000 cells/mm3, confirmed on repeat testing.
  • Total fasting cholesterol ≥ 280 mg/dL, confirmed on repeat testing.
  • Fasting LDL ≥ 180 mg/dL, confirmed on repeat testing.
  • Positive Hepatitis B surface antigen or Hepatitis B core antibody. Note: Individuals with a positive Hepatitis B core antibody will be excluded even in the presence of a positive Hepatitis B surface antibody due to the risk of reactivation.
  • Positive for Hepatitis C at the time of Screening. Note: treated or cleared Hepatitis C is not exclusionary.
  • Symptomatic herpes zoster infection (i.e., visible herpetic skin lesions of Zoster) within 3 months prior to study screening, or any history of disseminated/complicated herpes zoster or herpes simplex infection (e.g., VZV encephalitis).
  • History of untreated latent tuberculosis infection (diagnosed with QuantiFERON-TB Gold Plus testing) or active tuberculosis whether treated or untreated. Note: those with a positive PPD who have a history of BCG vaccine and a negative QuantiFERON-TB Gold Plus test will remain eligible).
  • History of current or recent (< 30 days from screening) sepsis or clinically significant viral, bacterial, fungal, or parasitic infection, according to the determination of the investigator.
  • Participants with HIV will be excluded if they have been on ART <1 year, have a CD4+ T cell count <500 cells/ml (confirmed on repeat), or have two consecutive HIV plasma RNA viral load > 48 copies/mL within 1 year of study screening, including requiring the most recent within 3 months of screening. Blips (VL > 48 copies/mL but < 200 copies/mL) are permitted if preceded and followed by values below the assay limit of quantification.
  • Immunocompromised as defined by NIH COVID-19 guidelines (see Appendix) and, in the opinion of the investigator, at an unacceptable risk for participating in the study.
  • Treatment with another investigational drug or device as part of an interventional study within 30 days of study screening.
  • In the opinion of the investigator, unable to reliably follow-up for the duration of the study and/or are unable to follow study restrictions/procedures.
  • Persons of childbearing potential under age 55 who are unwilling or unable to abstain from sex or to use at least one acceptable method of contraception from the time of screening though at least 28 days after the end of the study intervention period. Note: Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), other contraceptives, oral contraceptive pills, and surgical sterilization. Participants unwilling to be counseled about risks related to pregnancy or breastfeeding.
  • Currently pregnant or breastfeeding or planning to become pregnant or breastfeed during the course of the study.
  • Participants actively breastfeeding, who are unwilling to stop breastfeeding for the duration of the trial.
  • Currently incarcerated
  • NOTE RE: History of major adverse cardiovascular event (MACE) or traditional risk factors including smoking. For REVERSE-LC, MACE is defined as acute myocardial infarction and stroke. The study team will discuss the risks and benefits of baricitinib and CV events with the participant prior to study entry.
  • NOTE RE: EBV/CMV Seropositivity - The investigators will not exclude participants based on EBV or CMV seropositivity. The investigators already know that serologic evidence suggesting recent EBV reactivation is associated with Long COVID fatigue and high level EBV responses are associated with neurocognitive Long COVID, but that EBV viremia and IgM is rare. The investigators believe there is equipoise with regard to the potential effects of baricitinib on EBV - it is as likely that inflammation drives EBV reactivation, just as EBV can drive inflammation. For this reason, the investigators think this is best studied as a biological factor correlated with outcomes and that the investigators should not deliberately include or exclude people based on this. CMV seropositivity is associated with improved Long COVID outcomes. Results are not required for screening.

Trial locations and contacts

17 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Amanda Bistran-Hall contact

615-343-8010

vccrvlcstudy@vumc.org

Wes Ely, M.D. contact

17 sites in 1 country

United States17 sites, 17 recruiting

  • Emory University

    Atlanta, Georgia, 30322

    Vincent Marconi, MD, (404) 727-2343, vcmarco@emory.edu

    Recruiting

  • University of Colorado I Anschutz Medical Campus

    Aurora, Colorado, 80045

    Sarah Jolley, MD, (303) 724-2902, sarah.jolley@cuanschutz.edu

    Jeff McKeehan, MSN, AC-AGNP, (303) 724-6080, jeffrey.mckeehan@cuanschutz.edu

    Recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Lindsey R Baden, MD, 6175257327, vaccines@partners.org

    Recruiting

  • NYU Langone Health - Brooklyn

    Brooklyn, New York, 11220

    Jennifer Frontera, MD, (718) 630-6689, Jennifer.Frontera@nyulangone.org

    Zariya Alvarez, MPH, (917) 613-5770, zariya.alvarez@nyulangone.org

    Recruiting

  • Illinois Research Network (ILLInet), University of Illinois Chicago

    Chicago, Illinois, 60608

    Jerry A Krishnan, MD, PhD, (833) 847-4577, reverse-lc@uic.edu

    Sarah Darski, MPH, (833) 847-4577, reverse-lc@uic.edu

    Recruiting

  • University Hospitals Cleveland Case Western

    Cleveland, Ohio, 44106

    Grace McComsey, MD, (216) 368-3731

    Danielle Labbato, BSN, RN, (216) 844-2739, Danielle.Labbato@uhhospitals.org

    Recruiting

  • The MetroHealth System

    Cleveland, Ohio, 44109

    Nora Singer, MD, (216) 778-3693, nsinger@metrohealth.org

    Emma Barnboym, BSNs, (216) 778-3752, ebarnboym@metroHealth.org

    Recruiting

  • University of Florida College of Medicine

    Gainesville, Florida, 32610

    Nicole Iovine, MD, PhD, (352) 273-5481, nicole.iovine@medicine.ufl.edu

    Alexandra Taylor, MS, (352) 294-4248, tayloralexandra@ufl.edu

    Recruiting

  • University of California, Los Angeles (UCLA)

    Los Angeles, California, 90024

    Priscilla Y Hsue, MD, phsue@mednet.ucla.edu

    Veronica L Schaffer, vschaffer@mednet.ucla.edu

    Recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    Carolyn Bramante, MD, MPH, (651) 717-8915, bramante@umn.edu

    Recruiting

  • West Virginia Clinical and Translational Science Institute

    Morgantown, West Virginia, 26506-7015

    Madison Heltzel (nee Kelley), RN, BSN, (304) 293-6360, macey.kelley@hsc.wvu.edu

    Tara Riddle, BA, MSW, (304) 581-1829, tlr0011@hsc.wvu.edu

    Recruiting

  • Vanderbilt University Medical

    Nashville, Tennessee, 37203

    Matthew Mart, MD, MSCI, (615) 322-0184, matthew.f.mart@vumc.org

    Recruiting

  • Yale University

    New Haven, Connecticut, 06510

    Basmah Safdar, MD, (475) 306-5688, rvlcyale@yale.edu

    Anirudh Goyal, MPH, anirudh.goyal@yale.edu

    Recruiting

  • University of Texas at San Antonio

    San Antonio, Texas, 78229

    Thmas F Patterson, MD, (210) 567-4810, patterson@uthscsa.edu

    Barbara S Taylor, MD, (210) 567-4823, taylorBS4@uthscsa.edu

    Recruiting

  • University of California San Francisco

    San Francisco, California, 94143

    Michael Peluso, MD, (617) 910-0584, Michael.Peluso@ucsf.edu

    Recruiting

  • Swedish Medical Center

    Seattle, Washington, 98104

    Jason Goldman, MD, MPH, (206) 386-3660, jason.goldman@swedish.org

    Allie Duven, BSN, (206) 337-3864, RDResearch@providence.org

    Recruiting

  • University of Arizona

    Tucson, Arizona, 85724

    Sairam Parthasarathy, MD, (520) 626-8309, spartha1@arizona.edu

    Arianna Bedoya, MPH, (520) 626-1590, aresendiz@arizona.edu

    Recruiting

Other trials in United States

About this study

Official title: Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID (REVERSE-LC)

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.

Read the detailed description

Since the emergence of the severe acute respiratory syndrome coronavirus 2 pathogen in late 2019, there have been over 680 million cases worldwide and over 6 million deaths. In the United States alone, there have been over 100 million cases and over 1 million deaths. Both novel vaccines and effective therapeutics have helped reduce mortality in well-resourced countries. Despite these advances, millions of patients subsequently experience a devastating post-acute infection syndrome known as post-acute sequelae of SARS-CoV-2 infection (PASC), or better known by patients as Long COVID (LC). In the United States alone, it is estimated that up to 18 million adults suffer from LC with persistent neurocognitive impairments (NCI) and cardiopulmonary symptoms such as dyspnea and exercise intolerance for months to years after acute COVID-19. Additionally, up to 1 in 5 patients who were working prior to contracting SARS-CoV-2 may not return to the workforce due to cognitive and physical impairments. The public health burden of LC is estimated to be the largest seen from an emerging disease in the last 100 years, yet there are currently no effective interventions.

These clear and objective changes in cognitive function and brain structure highlight the devastating and long-lasting effects of SARS-CoV-2 infection on survivors' long-term health, highlighting the need for effective therapies to improve long-term cognitive outcomes.

In addition to the devastating NCI that patients with LC experience, many survivors go on to experience activity-limiting dyspnea on exertion, exercise intolerance, and reduced physical function. In fact, patients who have not fully recovered physically 5 months after infection may fail to recover further by one year. Patients with LC experience significant self-reported physical symptoms including persistent fatigue and dyspnea as well as objective impairments in exercise capacity and physical function upon performance testing. These impairments, in addition to cognitive function and mental health, lead to significant reductions in quality of life for these survivors.

While viral reservoirs, systemic and organ-level inflammation are leading hypotheses for the mechanistic underpinnings of LC, no trials to date have investigated the use of agents targeting these mechanisms. Similar chronic inflammation plays a crucial role in the increased risk of cardiovascular disease (CVD) and NCI for people with HIV (PWH) as indicated by elevated soluble and cellular markers of inflammation, endothelial dysfunction, and hypercoagulability in this population. Activation of the Janus kinase (JAK)-STAT pathway, which drives a proinflammatory milieu, has been reported during HIV infection and is associated with CVD, NCI, and HIV persistence. Even in the absence of a viral infection, these same conditions and comorbidities are driven by a very similar chronic inflammatory state.

Being tested
Baricitinib, Placebo
Keywords
COVID-19, Long COVID Drug Treatment, Long COVID
Medical subject headings
Post-Acute COVID-19 Syndrome, COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BaricitinibDrug

    Also called OLUMIANT

    4mg encapsulated, pre-formed tablet PO once daily for 24 weeks.

  • PlaceboOther

    Matched placebo capsule, PO once daily for 24 weeks.

Study groups in NCT06631287
Study groupRoleWhat they receive
BaricitinibExperimentalJanus kinase inhibitor
Receives: Drug: Baricitinib
PlaceboPlacebo comparatorPlacebo
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Month 6

Secondary outcomes (14)

  1. Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 6-months.

    CNS-Vital Signs Global Cognitive Index 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.

    Measured: Month 6

  2. Objective neuropsychological function domains of executive function, memory, processing speed, and motor speed including the CNS-Vital Signs subscale tests at 12-months.

    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.

    Measured: Month 12

  3. Modified Everyday Cognition (mECog)

    Subjective participant-reported cognitive impairment including modified Everyday Cognition (mECog) scale at 3-, 6-, and 12-months.

    The mECog measure uses the sum score of all of the subscales, and the items are reverse coded (i.e., 1= "Better or no change", 2="Questionable/occasionally worse", 3="Consistently a little worse", 4="Consistently much worse"), meaning that lower scores are better. Reported total scores range from 39 (Better or no change) to 156 (Consistently much worse).

    Measured: Months 3, 6 and 12

  4. Exercise capacity including the 6-minute walk test (6MWT) at 6- and 12-months

    Total distance in meters walked in 6 minutes

    Measured: Months 6 and 12

  5. Cardiopulmonary exercise testing (CPET)

    Cardiorespiratory fitness (peak VO2) using cardiopulmonary exercise testing (CPET) at 6- and 12- months. CPET is used to assess change in exercise tolerance as measured by VO2max.

    Measured: Months 6 and 12

  6. Quality-of-life measures including the EuroQOL-5D-5L at 3-, 6-, and 12-months

    The 5-Level EuroQol-5D health questionnaire (EQ-5D-5L) is a standardized instrument for use as a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The index value total (which is country-specific) ranges from a minimum value of -1 to a maximum value of +1. A higher EQ-5D-5L index value represents better quality of life (QoL), thus a positive change in the index value represents improved QoL.

    Measured: Months 3, 6, and 12

  7. Post-exertional malaise including the modified De Paul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM) at 6- and 12-months

    The mDSQ-PEM has 10 questions (5 on severity and 5 on frequency) scored 0-4, with higher scores indicating greater post exertional malaise severity.

    Measured: Months 6 and 12

  8. Effect of breathlessness on daily activities including the Modified Medical Research Council Dyspnea Scale (mMRC) at 6- and 12-months

    Modified Medical Research Council Dyspnea Scale (mMRC) ranges from grade 0 to 4. 0 means no dyspnea, 1 means mild dyspnea (respiratory distress when moving quickly and climbing slightly uphill); 2 means moderate dyspnea (walking slower than peers when walking straight on, stopping to breathe); 3 means severe dyspnea (stopping to breathe after walking about 100 m or for a few minutes) and 4 means very severe dyspnea (getting out of breath while doing daily chores at home, while putting on and taking off clothes and while going to toilet).

    Measured: Months 6 and 12

  9. Post COVID-19 symptom burden including the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale at 1-, 3-, 6-, and 12-months

    The SBQ-LC Circulation Subscale consists of 5 questions with a score of 0-11 where higher scores indicate greater circulation-related symptom burden.

    Measured: Months 1, 3, 6, and 12

  10. General participant-reported outcomes using the PROMIS-29 at 1-, 3-, 6-, and 12-months

    The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 has 29 questions across seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) each scored 1-5, with higher scores indicating worse symptoms or better function, depending on the domain.

    Measured: Months 1, 3, 6, and 12

  11. Cognitive participant-reported outcomes using the PROMIS-Cognitive Function-Short Form 8a at 1-, 3-, 6-, and 12-months

    The Patient-Reported Outcomes Measurement Information System-Cognitive Function-Short Form 8a (PROMIS-CF-8a) has 8 questions, each scored 1-5, with higher scores indicating better cognitive function.

    Measured: Months 1, 3, 6, and 12

  12. Mental health measures including depression, anxiety, and stress using the DASS-21 at 6- and 12-months

    The Depression Anxiety Stress Scale (DASS)-21 is a set of three (depression, anxiety, stress) self reported scales. Depression: Normal 0-9, Mild 10-13, Moderate 14-20, Severe 21-27, Extremely Severe 28+. Anxiety Normal 0-7, Mild 8-9, Moderate 10-14, Severe 15-19, Extremely Severe 20+. Stress Normal 0-14, Mild 15-18, Moderate 19-25, Severe 26-33, Extremely Severe 34+.

    Measured: Months 6 and 12

  13. Orthostatic intolerance using the Orthostatic Intolerance Questionnaire (OIQ) at 3-, 6-, and 12-months

    Each subscale is scored on a 0-10 scale, with higher scores reflecting more severe symptoms compared to few/no symptoms at lower scores. The OISA has a total possible score of 40 and the OIDAS a total possible score of 60.

    Measured: Months 3, 6, and 12

  14. Autonomic dysfunction using the COMPASS-31 at 3-, 6-, and 12-months.

    The Composite Autonomic Symptom Score (COMPASS)-31 has 31 questions across six health domains (orthostatic Intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor), scored 0-4 with higher scores indicating greater autonomic symptom burden.

    Measured: Months 3, 6, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2024
  2. Study start21 Oct 2024
  3. Primary completion1 Nov 2026 (estimated)
  4. Study completion1 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Investigators will use adequate allocation concealment using a computer-generated, permuted-block randomization with varying block size. Randomization (1:1) will be stratified by site, SARS CoV-2 confirmatory test (cohort 1), and opting into the LP sub-study. The block size and treatment allocation will only be known to a biostatistician creating the randomization list and the study pharmacist and will not be shared with trial investigators or any other study personnel.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
550 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06631287
Sponsor's protocol ID
REVERSE-LC
Other IDs
R01AG085873
Acronym
REVERSE-LC
Status last verified
Sep 2026
First submitted
4 Oct 2024
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Baricitinib in people with Long COVID and Sars-CoV-2 Infection, run by Wes Ely at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Amanda Bistran-Hall (615-343-8010, vccrvlcstudy@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CNS-Vital Signs Global Cognitive Index (time frame: Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06631287.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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