Clinical trial NCT05858515: REVERSE-Long COVID-19 With Baricitinib Study
Official title: REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (With Baricitinib) for Long COVID Related Cognitive Impairment and ADRD (Alzheimer's Disease and Related Dementias)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Post-Acute COVID-19 Syndrome
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Emory University
name: University of California, San Francisco
name: University of Minnesota
name: Vanderbilt University
name: Yale University
First posted: 2023-05-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled, double-blind, parallel-design superiority design
Primary purpose: TREATMENT

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.

Eligibility criteria: In order to be eligible to participate in this study, an individual must meet all of the following 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

Primary outcomes:
measure: Enrollment
timeFrame: 6 months
measure: Diversity in enrollment
timeFrame: 6 months
measure: Study drug prescribed
timeFrame: 9 months
measure: Study withdrawals
timeFrame: 18 months
measure: Adverse event reporting
timeFrame: 18 months
measure: Study dosing
timeFrame: 9 months
measure: Study completion
timeFrame: 18 months
Secondary outcomes:
measure: Severe and Serious Adverse Events
timeFrame: 9 months
measure: Premature study discontinuation
timeFrame: 9 months
measure: Global Neuropsychological Function
timeFrame: 9 months
measure: Cardiopulmonary testing
timeFrame: 9 months
measure: Everyday Cognition
timeFrame: 9 months
measure: Functional Status
timeFrame: 9 months
measure: Quality of Life Measures
timeFrame: 9 months
measure: Post-Exertional Malaise
timeFrame: 9 months
measure: Shortness of Breath
timeFrame: 9 months
measure: Symptom Burden
timeFrame: 9 months
measure: Inflammation biomarkers
timeFrame: 9 months
measure: Viral Reservoirs
timeFrame: 9 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: E. Wesley Ely, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: