REVERSE-Long COVID-19 With Baricitinib Study

NCT ID: NCT05858515

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-21
• Study Completion Date: 2029-12-30

Brief Summary

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.

Detailed Description

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.

Conditions

Post-Acute COVID-19 Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

These participants will receive placebo for 24 weeks (6 mo)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Intervention #1

These participants will receive baricitinib 4 mg daily for 24 weeks

Group Type: EXPERIMENTAL

Baricitinib 4 MG

Intervention Type: DRUG

Nonproprietary name: Baricitinib

Interventions

Baricitinib 4 MG

Nonproprietary name: Baricitinib

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Olumiant

Eligibility Criteria

Inclusion Criteria

1. Obtain a signed and dated informed consent form from participant

2. State their willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged ≥18 years old

4. Meet the following criteria for "Post-COVID Condition" or Long COVID:

1. 6-months prior, documented SARS-CoV-2 infection

2. Cognitive impairment as defined by having at least 20% positive (worse or much worse) items on the ECOG assessment

3. Neurocognitive symptoms must have been present for at least 60 days prior to screening. Symptoms that wax and wane must have been initially present at least 60 days prior to screening.

5. Ability to take oral medication and be willing to adhere to the baricitinib regimen

6. Females of childbearing potential must agree to either abstinence or 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), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pre-existing cognitive impairment not exacerbated by acute COVID as determined by study physicians after thorough review of participant's history and medical records

2. Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs)

3. Known allergic reactions to components of the baricitinib

4. Have ever been randomized in this study or any other study investigating baricitinib

5. Positive SARS-CoV-2 PCR or rapid Antigen test in the past 14 days

6. Pregnancy or breastfeeding

7. Any history of venous thromboembolism ever

8. History of malignancy or lymphoproliferative disorder

9. Renal dysfunction with estimated glomerular filtration rate of < 30 mL/min/1.73m2

10. Absolute Neutrophil Count (ANC) <1200 cells/mm3

11. History or evidence of severe or end-stage liver disease (e.g. bilirubin ≥1.5x or AST/ALT >2x normal).

12. Positive Hepatitis B surface antibody, antigen or core antibody, or Positive Hepatitis C RNR or antigen

13. Positive HIV 4th generation (antibody/antigen) ELISA test

14. Have had symptomatic herpes zoster infection within 3 months prior to study entry or have a history of disseminated/complicated herpes zoster or herpes simplex infection

15. History of latent (diagnosed with Quantiferon testing) or active tuberculosis

16. History of a current or recent (< 30 days from screening) clinically significant viral, bacterial, fungal, or parasitic infection

17. History of chronic alcohol abuse, Intravenous (IV) drug abuse, or other illicit drug abuse within the 2 years prior to study entry

18. Are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study

19. Treatment with another investigational drug or other intervention < 30 days of study enrollment

20. Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures

21. Severe cognitive, physical, or psychological disability that would prevent participation in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Wes Ely

Co-Director, Critical Illness, Brain Dysfunction, and Survivorship Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

E. Wesley Ely, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

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

Vanderbilt University

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

U13800

Identifier Type: -

Identifier Source: org_study_id