Baricitinib for Post-COVID Syndrome

(REVERSE-LC Trial)

Recruiting at 3 trial locations

Overseen By Wes Ely, M.D.

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

Trial Summary

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.

What data supports the effectiveness of the drug Baricitinib for Post-COVID Syndrome?

Research shows that Baricitinib, a drug that reduces inflammation, has been effective in improving lung function and reducing severe symptoms in COVID-19 patients, especially when used with other treatments like corticosteroids. ^{1 2 3 4 5}

Is baricitinib safe for humans?

Baricitinib has been studied for safety in hospitalized adults with COVID-19, showing it is generally safe when used with standard care. It is an oral medication that helps reduce inflammation and has been used in various trials without major safety concerns. ^{1 2 3 6 7}

How is the drug baricitinib unique for treating post-COVID syndrome?

Baricitinib is unique because it is an oral medication that works by inhibiting Janus kinase (JAK) enzymes, which can help reduce inflammation and block viral entry into cells. This mechanism is different from other treatments that may not target these specific pathways, making it potentially effective for improving respiratory function in post-COVID syndrome. ^{2 3 4 5 6}

What is the purpose of this trial?

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.

Research Team

Wes Ely, M.D.

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

References

1. England 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]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Baricitinib improves respiratory function in patients treated with corticosteroids for SARS-CoV-2 pneumonia: an observational cohort study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Use of baricitinib in treatment of COVID-19: a systematic review. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab. [2022]

6. England 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Tocilizumab vs. baricitinib in hospitalized severe COVID-19 patients: results from a real-world cohort. [2023]