Long Covid (LC)-REVITALIZE - A Long Covid Repurposed Drug Study
ConditionLong COVID
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-65
SponsorDouglas D. Fraser
About this trial
The Long-Covid (LC)-Revitalize clinical study is testing repurposed drug treatments for Long Covid, involving adult participants from Brazil, Canada, Italy, Uganda, the United States, and Zambia. To qualify, participants must have had Covid-19 and experienced Long Covid symptoms for at least three months. The main goal of the study is to determine whether the drug treatments can improve symptoms in five key areas: 1) fatigue, 2) breathing, 3) memory, thinking, and communication, 4) muscle and joint pain, and 5) circulation. A secondary goal is to assess changes in the body, such as reducing inflammation, as well as to confirm the safety and tolerability of the treatments. In the first phase, 348 participants will take either one of two existing medications (upadacitinib or pirfenidone) or a placebo (a pill with no active ingredient) for three months. Although these medications are not yet approved for Long Covid, they are authorized for use in treating other health conditions. This study is adaptive, meaning it may adjust based on early results. In the second phase, the study could continue testing the most effective drug(s) against a placebo with new participants, explore combinations of drugs to see if they improve results, or discontinue the drugs if they prove ineffective or unsafe and test alternative treatments.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adults ≥ 18 years of age and ≤ 65 years of age
Fatigue
Breathing
Circulation
Disqualifiers
Participants who do not meet the criteria outlined above
Participants who are unable to provide their informed consent
Participants who are pregnant, lactating, or plan to become pregnant during the time of the study
Persons of childbearing potential who are unwilling or unable to abstain from sex or to use at least one acceptable method of contraception from the time of screening through at least 30 days after the end of the study intervention period. Acceptable methods include barrier contraceptives (e.g., condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. Participants unwilling to be counseled about the risks related to pregnancy or breastfeeding will also be excluded.
Trial design
Design model
Parallel
Treatments tested in this trial
Pirfenidone
DrugInitial dose titration: First week (days 1-7): 1 capsule (267 mg), 3 times daily (801 mg/day) Second week (days 8-14): 2 capsules (534 mg), 3 times daily (1602 mg/day) Maintenance dose: Third week and thereafter (days 15+): 3 capsules (801 mg), 3 times daily (2403 mg/day)
Placebo for pirfenidone
DrugFirst week (days 1-7): 1 capsule, 3 times daily Second week (days 8-14): 2 capsules, 3 times daily Third week and thereafter (days 15+): 3 capsules, 3 times daily
Upadacitinib
Drug1 capsule (15 mg), once daily for 3 months
Placebo for upadacitinib
Drug1 capsule, once daily for 3 months
Treatment groups
348 Participants
are divided into 4 treatment groupsGroup A: PirfenidoneExperimental treatment 1 intervention
Group B: Placebo for PirfenidonePlacebo comparator 1 intervention
Group C: UpadacitinibExperimental treatment 1 intervention
Group D: Placebo for UpadacitinibPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Symptom Burden Questionnaire (SBQ) Subscales
The aim of this study is to evaluate the efficacy of two repurposed drugs in reducing symptom severity in participants with Long Covid. The change in symptom score (transformed scale of 0-100) from baseline to both the interim and final analyses will be compared across one of the five validated subscales, relative to the placebo. This study will utilize five validated subscales: 1) Fatigue, 2) Breathing, 3) Memory, Thinking, and Communication, 4) Muscles and Joints, and 5) Circulation. Each subscale is based on a 4-point ordinal scale that assesses frequency, severity, or interference, or it uses a dichotomous yes/no response. The subscale with the highest symptom burden, determined by the highest transformed symptom score (ranging from 0 to 100, with a higher score indicating greater symptom burden) at baseline, will be selected for evaluating treatment effects.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.Secondary outcomes
1
General participant reported overall well-being using the Patient Reported Outcome Measurement Information System (PROMIS)-29 questionnaire
To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Patient Reported Outcome Measurement Information System (PROMIS)-29 questionnaire. The PROMIS-29 questionnaire consists of 29 items covering an overview of the participant's physical, mental, and social health. Each item is scored on a scale of 1 to 5, with the interpretation of lower scores varying by domain-indicating either better or worse symptom experience.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.2
General participant reported overall well-being using the Generalized Anxiety Disorder (GAD)-7 questionnaire
To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Generalized Anxiety Disorder (GAD)-7 questionnaire from baseline to the interim and final analyses. The GAD-7 questionnaire consists of 7 items relating to the symptoms of stress and anxiety levels. Each item is scored on a scale of 0-3 with higher scores indicating more severe symptoms. Overall scores can range from 0-21 with scores of 5, 10, and 15 taken as the cut-off points for mild, moderate, and severe anxiety, respectively.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.3
General participant reported overall well-being using the Patient Health Questionnaire (PHQ)-9
To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Patient Health Questionnaire (PHQ)-9 from baseline to the interim and final analyses. The PHQ-9 questionnaire consists of 9 items related to the symptoms of depression. Each item is scored on a scale of 0-3 with higher scores indicating more severe symptoms. Overall scores can range from 0-27 with scores of 5, 10, 15, and 20 taken as cut off points for mild, moderate, moderately severe, and severe depression, respectively.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.4
General participant reported severity of post-exertional malaise (PEM) using the FUNCAP27 questionnaire
To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in scores of the Functional Capacity (FUNCAP)27 questionnaire from baseline to the interim and final analyses. The FUNCAP27 questionnaire consists of 27 items related to assessing functional capacity and the consequences of performing activities. Each item is scored on a scale of 0-6, with 0 indicating the participant is unable to complete the activity and 6 indicating the activity is unproblematic and does not affect other activities.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.Other outcomes
1
A comprehensive OMICS evaluation will be completed to further understand mechanisms of the repurposed drugs
Plasma proteomics will be analyzed to assess protein differential expression and signaling pathway mechanisms related to the study drugs. Analyses will focus on the expression normalization of proteins/pathways associated with Long Covid. Plasma metabolomics will be analyzed to evaluate metabolic changes and the overall effects of the study drugs. Analyses will focus on the concentration normalization of metabolites linked to the pathophysiology of Long Covid. White blood cell (WBC) RNA sequencing will be performed to identify changes in gene expression, offering insight into the body's response to the study drugs. Analyses will focus on transcriptional shifts from baseline to the end of the study. Exome sequencing and single nucleotide polymorphism (SNP) analysis will be performed to identify genetic variants that may influence the metabolism and efficacy of the study drugs. This will help identify genetic markers associated with drug non-responders.
Time frame
The Phase 1 time frame is from enrollment on Day 1 through to the end of follow-up at Month 6, and the Phase 2 time frame will be determined based on the results of Phase 1.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Douglas D. Fraser
Lead sponsor
Western University, Canada
Sponsor institution
Source ClinicalTrials.gov