REVERSE-Long COVID-19 With Baricitinib Study
- Conditions
- Post-Acute COVID-19 Syndrome
- Interventions
- Drug: Placebo
- Registration Number
- NCT05858515
- Lead Sponsor
- Vanderbilt University Medical Center
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- 550
Not provided
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
- History of latent (diagnosed with Quantiferon testing) or active tuberculosis
- History of a current or recent (< 30 days from screening) clinically significant viral, bacterial, fungal, or parasitic infection
- History of chronic alcohol abuse, Intravenous (IV) drug abuse, or other illicit drug abuse within the 2 years prior to study entry
- Are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study
- Treatment with another investigational drug or other intervention < 30 days of study enrollment
- Are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures
- Severe cognitive, physical, or psychological disability that would prevent participation in the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention #1 Baricitinib 4 MG These participants will receive baricitinib 4 mg daily for 24 weeks Placebo Placebo These participants will receive placebo for 24 weeks (6 mo)
- Primary Outcome Measures
Name Time Method Diversity in enrollment 6 months 40% of participants will be from individuals disproportionally affected by COVID (Black, Hispanic, Asian, American Indian)
Study withdrawals 18 months Less than 20% participants will be deemed lost to follow up
Study dosing 9 months 100% adherence to study drug dose adjustments guidelines
Enrollment 6 months 2 participants per month, on average, are randomized
Study drug prescribed 9 months 80% of participants received every prescribed dose of the study drug
Study completion 18 months 80% of participants adhere to all study procedures and requirements
Adverse event reporting 18 months 100% of Serious Adverse Events reported to Data Safety Monitoring Board within 24 hours of study team awareness
- Secondary Outcome Measures
Name Time Method Cardiopulmonary testing 9 months Assess percentage changes of exercise capacity (peak VO2) using cardiopulmonary exercise testing (CPET) in the baricitinib arm compared to the placebo arm from baseline to week 12
Symptom Burden 9 months Assess percentage changes of post COVID-19 symptom burden using the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale in the baricitinib arm compared to the placebo arm from baseline to week 12
Inflammation biomarkers 9 months Decreases in plasma biomarkers of inflammation in the baricitinib arm compared to placebo arm from baseline to week 12
Viral Reservoirs 9 months Decreases in viral reservoirs for the baricitinib arm compared to placebo arm from baseline to week 12
Severe and Serious Adverse Events 9 months Compare the percentage of severe and serious adverse events between study arms from baseline to week 12.
Global Neuropsychological Function 9 months Assess percentage changes of global neuropsychological function as measured using the CNS Vital Signs Neurocognition Index cognitive battery between baricitinib and placebo study arm from baseline to week 12.
Functional Status 9 months Assess percentage changes of functional status measures in the baricitinib arm compared to the placebo arm from baseline to week 12
Quality of Life Measures 9 months Assess percentage changes of quality of life measures in the baricitinib arm compared to the placebo arm from baseline to week 12
Post-Exertional Malaise 9 months Assess percentage changes of post-exertional malaise using De Paul Symptom Questionnaire - Post-Exertional Malaise (DSQ-PEM) in the baricitinib arm compared to the placebo arm from baseline to week 12
Premature study discontinuation 9 months Compare the rate of study drug/placebo premature discontinuation by study arm (tolerability)
Everyday Cognition 9 months Assess percentage changes of cognitive impairment using Everyday Cognition (ECog) scale in the baricitinib arm compared to the placebo arm from baseline to week 12
Shortness of Breath 9 months Assess percentage changes of the effect of breathlessness on daily activities using the Modified Medical Research Council Dyspnea Scale (mMRC) in the baricitinib arm compared to the placebo arm from baseline to week 12
Trial Locations
- Locations (6)
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