REVERSE-Long COVID-19 With Baricitinib Study

NCT05858515 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: U13800
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

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.

Conditions

Post-Acute COVID-19 Syndrome

Outcome Measures

Primary Outcomes (7)

• Enrollment

  2 participants per month, on average, are randomized

  6 months

• Diversity in enrollment

  40% of participants will be from individuals disproportionally affected by COVID (Black, Hispanic, Asian, American Indian)

  6 months

• Study drug prescribed

  80% of participants received every prescribed dose of the study drug

  9 months

• Study withdrawals

  Less than 20% participants will be deemed lost to follow up

  18 months

• Adverse event reporting

  100% of Serious Adverse Events reported to Data Safety Monitoring Board within 24 hours of study team awareness

  18 months

• Study dosing

  100% adherence to study drug dose adjustments guidelines

  9 months

• Study completion

  80% of participants adhere to all study procedures and requirements

  18 months

Secondary Outcomes (12)

• Severe and Serious Adverse Events

  9 months

• Premature study discontinuation

  9 months

• Global Neuropsychological Function

  9 months

• Cardiopulmonary testing

  9 months

• Everyday Cognition

  9 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Intervention #1

EXPERIMENTAL

These participants will receive baricitinib 4 mg daily for 24 weeks

Drug: Baricitinib 4 MG

Interventions

Baricitinib 4 MG DRUG

Nonproprietary name: Baricitinib

Also known as: Olumiant

Intervention #1

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pre-existing cognitive impairment not exacerbated by acute COVID as determined by study physicians after thorough review of participant's history and medical records
• Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs)
• Known allergic reactions to components of the baricitinib
• Have ever been randomized in this study or any other study investigating baricitinib
• Positive SARS-CoV-2 PCR or rapid Antigen test in the past 14 days
• Pregnancy or breastfeeding
• Any history of venous thromboembolism ever
• History of malignancy or lymphoproliferative disorder
• Renal dysfunction with estimated glomerular filtration rate of \< 30 mL/min/1.73m2
• Absolute Neutrophil Count (ANC) \<1200 cells/mm3
• History or evidence of severe or end-stage liver disease (e.g. bilirubin ≥1.5x or AST/ALT \>2x normal).
• Positive Hepatitis B surface antibody, antigen or core antibody, or Positive Hepatitis C RNR or antigen
• Positive HIV 4th generation (antibody/antigen) ELISA test
• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Emory University: collaborator
• University of California, San Francisco: collaborator
• University of Minnesota: collaborator
• Vanderbilt University: collaborator
• Yale University: collaborator

Study Sites (6)

University of California San Francisco

San Francisco, California, 30329, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Vanderbilt University

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-8300, United States

Location

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

baricitinib

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• E. Wesley Ely, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The block size and treatment allocation will only be known to the biostatistician creating the randomization list and will not be shared with trial investigators or any other study personnel. This list will be directly uploaded into REDCap's randomization module. This maintains the concealment of future allocations and has been used successfully for several of our large RCTs. The details of the randomization procedure including details regarding stratification and block sizes will fully be reported in the trial publication to enable readers to assess the risk of bias. Randomization assignments will be accessible 24 hours a day, 7 days a week to the study coordinators and staff
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Director, Critical Illness, Brain Dysfunction, and Survivorship Center

Model Details: Randomized, placebo-controlled, double-blind, parallel-design superiority design

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: May 15, 2023
• Study Start: October 21, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 30, 2029
• Last Updated: January 31, 2025

Record last verified: 2025-01

Locations

US (6)