Baricitinib for Post-COVID Syndrome

(REVERSE-LC Trial)

Recruiting at 3 trial locations

Overseen By Amanda Bistran-Hall

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Wes Ely

Must not be taking: Baricitinib, DMARDs, Probenecid

Disqualifiers: Cognitive impairment, Suicidality, Cardiovascular event, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

550 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if baricitinib, a medication, can improve brain and physical function, quality of life, and symptoms in individuals with Long COVID. Participants will receive either baricitinib or a placebo to compare effects. Suitable candidates have had a confirmed COVID-19 infection at least six months ago and continue to experience symptoms like fatigue or "brain fog" that impact daily life. As a Phase 3 trial, this study serves as the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using baricitinib, other similar drugs, or probenecid.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research has shown that baricitinib was well-tolerated in previous studies. In individuals with conditions like COVID-19, its safety profile was similar to its use for rheumatoid arthritis, indicating no new major safety issues for COVID-19. Common side effects included minor infections, with the risk of serious infections comparable to other treatments.

The FDA has already approved baricitinib for other uses, confirming it has passed strict safety tests. These findings can reassure prospective trial participants about the treatment's safety. Always consult a healthcare provider to understand the risks and benefits specific to your situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard treatments for post-COVID syndrome, which often focus on managing symptoms with supportive care and medications like steroids and antivirals, Baricitinib offers a fresh approach by targeting the underlying inflammation. Baricitinib is a Janus kinase inhibitor, which means it works by interfering with specific pathways that cause inflammation in the body. This unique mechanism of action could potentially reduce the chronic symptoms experienced by post-COVID patients more effectively than current options. Researchers are excited about Baricitinib because it represents a targeted strategy that could improve the quality of life for those struggling with lingering effects of COVID-19.

What evidence suggests that baricitinib might be an effective treatment for Long COVID?

Research has shown that baricitinib, which participants in this trial may receive, may help reduce symptoms of long COVID in some patients. It has improved survival rates in severe COVID-19 cases, suggesting it might also help with related conditions. Some studies indicate it can enhance brain function, a major issue in long COVID. Baricitinib blocks certain proteins that cause inflammation, potentially easing symptoms like tiredness and brain fog. Although some trials have yielded mixed results, the drug has generally shown benefits in improving patient outcomes. ^{1 6 7 8 9}

Who Is on the Research Team?

Wes Ely, M.D.

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals experiencing long-term symptoms after COVID-19, often referred to as Long COVID. Participants should have persistent neurological or cardiopulmonary issues like brain fog, fatigue, or shortness of breath. Specific eligibility criteria are not provided but typically include age limits and health status requirements.

Inclusion Criteria

Evidence of personally signed and dated informed consent document

Evidence of personally signed and dated informed consent document

Cognitive impairment present defined by having at least 20% positive items on the 41-item modified ECog questionnaire

Exclusion Criteria

Venous thromboembolism in the past 6 months prior to screening or felt to be at increased risk of thrombosis by the investigator

Participants actively breastfeeding

Currently incarcerated

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive baricitinib or placebo to evaluate its effect on neurocognitive and cardiopulmonary symptoms of Long COVID

6 months

Monthly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of neurocognitive function and exercise capacity

6 months

Quarterly visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview The study aims to see if Baricitinib can improve brain function and quality of life in people with Long COVID compared to a placebo (a substance with no therapeutic effect). It's a randomized trial where participants unknowingly receive either the real drug or placebo.

How Is the Trial Designed?

Group I: Baricitinib Experimental Treatment 1 Intervention

Janus kinase inhibitor

Group II: Placebo Placebo Group 1 Intervention

Placebo

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Wes Ely

Lead Sponsor

Trials

1

Recruited

550+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 159 hospitalized COVID-19 patients requiring oxygen support, both tocilizumab and baricitinib showed similar efficacy in terms of in-hospital mortality, progression to mechanical ventilation, and length of stay, indicating that either treatment can be effective when used alongside standard care.

However, tocilizumab was associated with a higher incidence of elevated liver enzymes (ALAT), suggesting a potential safety concern that may warrant further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab vs. baricitinib in hospitalized severe COVID-19 patients: results from a real-world cohort. Karolyi, M., Gruebl, A., Omid, S., et al.[2023]

Baricitinib, when used alone or in combination with other therapies, shows favorable outcomes for hospitalized patients with moderate to severe COVID-19, based on a systematic review of 19 studies.

The evidence suggests that baricitinib significantly improves clinical outcomes in patients with COVID-19 pneumonia, indicating its potential to become a standard treatment option as more data becomes available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of baricitinib in treatment of COVID-19: a systematic review. Sampath, A., Banerjee, A., Atal, S., et al.[2023]

In a phase 3 trial involving 1525 hospitalized adults with COVID-19, baricitinib combined with standard care significantly reduced 28-day all-cause mortality by 38.2% compared to placebo, indicating its potential efficacy in improving survival rates.

While there was no significant difference in disease progression between the baricitinib and placebo groups, the safety profile of baricitinib was comparable to standard care, suggesting it can be safely integrated into treatment regimens for COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Marconi, VC., Ramanan, AV., de Bono, S., et al.[2022]

A patient with severe respiratory failure due to COVID-19 showed significant improvement in respiratory function and radiological findings after receiving baricitinib at a dose of 4 mg per day for 2 weeks.

This case suggests that baricitinib may be an effective treatment option for patients with COVID-19 who do not respond to standard therapies like antiretroviral drugs and IL-6 antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab. Cingolani, A., Tummolo, AM., Montemurro, G., et al.[2022]

In a study of patients with moderate to severe SARS-CoV-2 pneumonia, the combination of baricitinib and corticosteroids significantly improved oxygen saturation levels compared to corticosteroids alone, with a mean difference of 49 in SpO2/FiO2 (P < 0.001).

Patients receiving baricitinib had a much lower need for supplemental oxygen at discharge (25.8% vs 62.0%) and one month later (12.9% vs 28.0%), indicating that baricitinib may enhance recovery from severe pneumonia caused by COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study. Rodriguez-Garcia, JL., Sanchez-Nievas, G., Arevalo-Serrano, J., et al.[2022]

In a large trial involving 8,156 hospitalized COVID-19 patients, baricitinib significantly reduced the risk of death by 13% compared to standard care alone, indicating its efficacy as a treatment option.

The overall evidence from multiple trials suggests that JAK inhibitors like baricitinib can reduce mortality in hospitalized COVID-19 patients by about 20%, with no significant safety concerns related to increased deaths or infections from non-COVID causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. [2023]

In a phase 3 exploratory trial involving 101 critically ill COVID-19 patients on mechanical ventilation, baricitinib significantly reduced 28-day all-cause mortality by 46% compared to placebo, indicating its potential efficacy in severe cases.

Baricitinib treatment also led to a 44% reduction in 60-day mortality, with no significant differences in ventilator-free days or hospital stay duration, suggesting it may improve survival without increasing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Ely, EW., Ramanan, AV., Kartman, CE., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05858515

REVERSE-Long COVID-19 With Baricitinib Study This is a multi-site randomized, placebo-controlled, double-blind, parallel-design REVERSE-LC phase 3 study. Individuals meeting inclusion criteria will be ...

2. solvecfs.org solvecfs.org/new-clinical-trial-will-test-how-baricitinib-improves-neurocognitive-function-in-patients-with-long-covid/

New Clinical Trial Will Test How Baricitinib Improves ... The overall goal of the REVERSE-LC trial will be to determine how much baricitinib improves neurocognitive function in people with Long Covid.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9231077/

The AI-Assisted Identification and Clinical Efficacy of ... In summary, baricitinib has shown the greatest mortality benefit in large numbers of COVID-19 patients in randomised clinical trials [72] while tocilizumab and ...

4. idsociety.org idsociety.org/science-speaks-blog/2025/therapeutic-updates-on-long-covid-where-things-stand-5-years-later/

Therapeutic updates on long COVID: Where things stand 5 ... However, extended treatment with this drug has reduced symptoms of long COVID in some patients. Other clinical trials with mixed results have ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04421027

NCT04421027 | A Study of Baricitinib (LY3009104) in ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9443639/

A Review of Safety Outcomes from Clinical Trials ... Short-term findings indicated that the risk of serious infections was similar in patients with AD or AA treated with baricitinib compared with ...

7. fda.gov fda.gov/media/143823/download

Baricitinib EUA Fact Sheet for HCP Overall, the safety profile observed in patients with COVID-19 treated with baricitinib was consistent with the safety profile in patients with rheumatoid ...

8. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00547-4/fulltext

Safety of baricitinib in vaccinated patients with severe and ... Our data, in light of existing evidence, do not suggest that vaccination status per se is a safety concern regarding baricitinib treatment for ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04340232

Safety and Efficacy of Baricitinib for COVID-19 This study plans to learn more about the effects of a medicine called baricitinib on the progression of COVID-19 (coronavirus disease of 2019), ...