Long Covid (LC)-REVITALIZE - A Long Covid Repurposed Drug Study

NCT06928272 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: LC-Revitalize
• Study Type: interventional
• Target: 348
• Locations: 6 countries
• Sites: 8

Brief Summary

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.

Conditions

Long COVID

Keywords

Post-Covid-19 Condition; Covid-19; SARS-CoV-2

Outcome Measures

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.

  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 (8)

• General participant reported overall well-being using the Patient Reported Outcome Measurement Information System (PROMIS)-29 questionnaire

  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.

• General participant reported overall well-being using the Generalized Anxiety Disorder (GAD)-7 questionnaire

  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.

• General participant reported overall well-being using the Patient Health Questionnaire (PHQ)-9

  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.

• General participant reported severity of post-exertional malaise (PEM) using the FUNCAP27 questionnaire

  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.

• Worsening Long Covid Symptoms Measured by SBQ Subscales

  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

  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.

Study Arms (4)

Pirfenidone

EXPERIMENTAL

267mg pirfenidone tablets, over encapsulated in hard-gelatin capsules

Drug: Pirfenidone

Placebo for Pirfenidone

PLACEBO COMPARATOR

Hard-gelatin capsules that are made to look and feel like the pirfenidone over encapsulated drug

Drug: Placebo for pirfenidone

Upadacitinib

EXPERIMENTAL

15 mg upadacitinib tablets, over encapsulated in hard-gelatin capsules

Drug: Upadacitinib

Placebo for Upadacitinib

PLACEBO COMPARATOR

Hard-gelatin capsules that are made to look and feel like the upadacitinib over encapsulated drug

Drug: Placebo for upadacitinib

Interventions

Pirfenidone DRUG

Initial 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 15-90): 3 capsules (801 mg), 3 times daily (2403 mg/day)

Also known as: Esbrit

Pirfenidone

Placebo for pirfenidone DRUG

First week (days 1-7): 1 capsule, 3 times daily Second week (days 8-14): 2 capsules, 3 times daily Third week and thereafter (days 15-90): 3 capsules, 3 times daily

Placebo for Pirfenidone

Upadacitinib DRUG

1 capsule (15 mg), once daily for 90 days

Also known as: Rinvoq

Upadacitinib

Placebo for upadacitinib DRUG

1 capsule, once daily for 90 days

Placebo for Upadacitinib

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years of age and ≤ 65 years of age
• Previous Covid-19 (SARS-CoV-2 infection) within the past four years, as determined by the site investigator using the following certainty scale (based on available clinical history and/or serologic data):
• Confirmed Infection (PCR or n-Capsid Test): Prior positive nasopharyngeal or salivary PCR test for Covid-19 (documented proof and/or verbal confirmation by participant) or has positive nucleocapsid antibodies results.
• Probable Infection (Antigen Test): Participant verbally confirms a prior positive rapid antigen test without PCR confirmation.
• Possible Infection (Viral Syndrome and Epidemiological Link): Participant verbally confirms experiencing symptoms consistent with Covid-19 infection and has an epidemiological link (i.e., exposure to a confirmed case) without any positive testing.
• \. Persistent or new symptoms diagnosed as "Long Covid" as defined by the World Health Organization; "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection (Covid-19), with these symptoms lasting for at least 2 months with no other explanation". This diagnosis may come from a healthcare professional experienced in Long Covid diagnosis, or the site investigator. These symptoms must be present for more days than not and must not have been present prior to the onset of SARS-CoV-2 (Covid-19) infection.
• \. At the time of screening, participants should be experiencing at least one of the following self-reported symptoms or symptom clusters. Participant has self-reported issues with:
• Fatigue
• Breathing
• Circulation
• Memory, thinking, and/or communication
• Muscles and/or joints
• These five symptoms or symptom clusters were selected based on unpublished data from the National Institutes for Health and Care Research (NIHR, United Kingdom) and their alignment with five validated SBQ scales. The selection was driven by their prevalence and their significant impact on quality of life as reported in symptom assessments.
• \. Participant has the ability and is willing to follow study procedures throughout the study
• \. Participant can provide informed consent

You may not qualify if:

• Participants who have any one or more of the following criteria at the time of enrollment will be excluded:
• 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.
• Male participants must take precautions to avoid impregnating a female while participating in this study. If a male participant's partner can become pregnant, she must use an effective and reliable form of birth control, as listed above, during the study and for 30 days after the male participant's last dose of the investigational product. Additionally, male participants must agree to use a latex condom during sexual activity with partners who could become pregnant.
• eGFR \<30 mL/min/1.73m2
• Moderate to severe liver dysfunction, defined as Bilirubin \> 1.5 x ULN or AST or ALT \> 2 x ULN
• Hemoglobin (Hbg) \< 8.0 g/dL
• Absolute neutrophil count (ANC) below 1,000 cells/mm³, confirmed with repeat testing
• Absolute lymphocyte count (ALC) below 500 cells/mm³
• Alkaline phosphatase (ALP) levels equal to or greater than three times the upper limit of normal (ULN)
• Creatine phosphokinase (CPK) levels equal to or greater than three times the ULN
• Platelet count below 100,000 cells/mm³, confirmed with repeat testing
• Platelet count above 500,000 cells/mm³, confirmed with repeat testing

Sponsors & Collaborators

• Douglas D. Fraser: lead

Study Sites (8)

Laura Rodriguez Research Institute

San Diego, California, 92101, United States

RECRUITING

Ini-Fiocruz

Rio de Janeiro, Rio de Janerio, 21040-900, Brazil

NOT YET RECRUITING

Institut de Recherches Cliniques de Montréal (IRCM)

Montreal, Quebec, H2W 1R7, Canada

RECRUITING

Centre de Recherche du CHUS (CRCHUS)

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

INMI Lazzaro Spallanzani IRCCS

Roma, Roma, 00149, Italy

NOT YET RECRUITING

Sapienza Università di Roma

Roma, Roma, 00185, Italy

NOT YET RECRUITING

Joint Clinical Research Centre (JCRC)

Kampala, Kampala, 10005, Uganda

NOT YET RECRUITING

University Teaching Hospital

Lusaka, Lusaka Province, 10100, Zambia

NOT YET RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

pirfenidone; upadacitinib

Condition Hierarchy (Ancestors)

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

• Douglas D Fraser, MD, PhD, FRCPC

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Perkin

CONTACT

1-519-685-8500; stephanie.perkin@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, FRCPC, Professor and Clinician Scientist

Model Details: This study employs an adaptive, platform study design, allowing for flexibility in the evaluation and management of various interventions within an overarching core protocol to identify the best performing drug. The adaptive framework is designed to maximize efficiency, improve participant outcomes, and accelerate decision-making based on pre-specified criteria.

Study Record Dates

• First Submitted: April 3, 2025
• First Posted: April 15, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (1); ZA (1); IT (2); UG (1); BR (1)