Could old drugs beat long COVID? new trial aims to find out
NCT ID NCT06928272
First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time
Summary
This Phase 3 trial tests two repurposed drugs—upadacitinib and pirfenidone—against a placebo in 348 adults with Long COVID. Participants from six countries will take the drugs for three months to see if they ease symptoms like fatigue, breathing trouble, memory issues, muscle pain, and circulation problems. The study is adaptive, meaning it may adjust based on early results.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- upadacitinib and pirfenidone
- What this could lead to
- If successful, this could provide a safe, approved treatment option to reduce Long COVID symptoms like fatigue, brain fog, and pain.
- What could go wrong
- This is still an early Phase 3 trial with 348 participants. The drugs are not yet proven for Long COVID, and side effects or lack of benefit are possible.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 3
Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.
- Participants
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About 348 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Sep 2025
- Expected to finish
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Dec 2027
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 to 65 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: Eligible participants must meet all the following inclusion criteria: 1. Adults ≥ 18 years of age and ≤ 65 years of age 2. 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): 3 - 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. 2 - Probable Infection (Antigen Test): Participant verbally confirms a prior positive rapid antigen test without PCR confirmation. 1 - 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. 3\. 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. 4\. 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: 1. Fatigue 2. Breathing 3. Circulation 4. Memory, thinking, and/or communication 5. 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. 5\. Participant has the ability and is willing to follow study procedures throughout the study 6\. Participant can provide informed consent Exclusion Criteria: Participants who have any one or more of the following criteria at the time of enrollment will be excluded: 1. Participants who do not meet the criteria outlined above 2. Participants who are unable to provide their informed consent 3. Participants who are pregnant, lactating, or plan to become pregnant during the time of the study 4. 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. 5. 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. 6. eGFR \<30 mL/min/1.73m2 7. Moderate to severe liver dysfunction, defined as Bilirubin \> 1.5 x ULN or AST or ALT \> 2 x ULN 8. Hemoglobin (Hbg) \< 8.0 g/dL 9. Absolute neutrophil count (ANC) below 1,000 cells/mm³, confirmed with repeat testing 10. Absolute lymphocyte count (ALC) below 500 cells/mm³ 11. Alkaline phosphatase (ALP) levels equal to or greater than three times the upper limit of normal (ULN) 12. Creatine phosphokinase (CPK) levels equal to or greater than three times the ULN 13. Platelet count below 100,000 cells/mm³, confirmed with repeat testing 14. Platelet count above 500,000 cells/mm³, confirmed with repeat testing 15. Total fasting cholesterol levels of 280 mg/dL or higher, confirmed with repeat testing 16. Fasting low-density lipoprotein (LDL) levels of 180 mg/dL or higher, confirmed with repeat testing 17. A personal or family history of long QT syndrome or an electrocardiogram (ECG) during screening showing a corrected QT interval (QTc) of 500 milliseconds or greater, calculated using Fridericia's formula 18. Participants with HIV diagnosis 19. Participants with active hepatitis B or C diagnosis. Note: treated or cleared hepatitis C is not exclusionary. 20. Active herpes zoster infection (visible skin lesions) within 3 months prior to screening, or any history of disseminated or complicated herpes zoster or herpes simplex infection (e.g., VZV encephalitis) 21. Participants with active or latent tuberculosis 22. Immunocompromised status, as determined by the investigator, that places the participant at an unacceptable risk for study participation 23. Active malignancy or lymphoproliferative disorder that has not been in remission for at least five years. Localized non-melanoma skin cancers that have been definitively treated are not exclusionary. 24. Positive SARS-CoV-2 test in the last 30 days or symptomatic with Covid-19 like illness 25. Previous admission to an intensive care unit (ICU) for the treatment of acute COVID-19 infection 26. Any history of deep venous thrombosis, pulmonary embolism, unstable angina, atrial fibrillation, ventricular fibrillation, or myocardial infarction or stroke 27. History of sepsis or a significant viral, bacterial, fungal, or parasitic infection within 30 days prior to enrollment, as determined by the investigator. 28. Use of one or more of the study drugs within 30 days prior to enrollment for the original indication or other purposes 29. Known allergic reactions to the components of the study drugs 30. Any prior exposure to JAK inhibitors 31. Taking any of the listed medications on the prohibited medications list in Appendix A 32. Intake or planned consumption of any of the following: Taurine, Curcumin, CoQ10, Creatine, Resveratrol, Fisetin, Nicotinamide mononucleotide (NMN), Nicotinamide adenine dinucleotide (NAD+), Quercetin, Glycine, Spermidine, Arginine alpha-ketoglutarate, Ergothioneine, Alpha Lipoic Acid, Carnitine, Benfotiamine, Carnosine, Crocin, N-acetylcysteine 33. Covid vaccinations are prohibited within 30 days prior to enrollment 34. Live vaccine within the 30 days before enrollment or plan to receive live vaccines during the study period 35. Other vaccines, including influenza vaccine, are prohibited within 14 days of enrollment 36. Major surgery within 30 days prior to enrollment or plans for major surgery during the study 37. Any other co-existing medical condition or concomitant medication/therapy that might in the judgment of the study investigators, potentially impact the participant's safety or ability to adhere to the study protocol or interfere with the meaning of the clinical and research measurements as judged by the study investigators 38. Participation in any clinical study within the last 30 days prior to enrollment 39. Participants who participated in Phase One of this study (LC-Revitalize) are not eligible to participate in Phase Two 40. Currently hospitalized and/or incarcerated
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
9 sites in 6 countries. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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Centre de Recherche du CHUS (CRCHUS)
RECRUITINGSherbrooke, Quebec, J1H 5N4, Canada
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INMI Lazzaro Spallanzani IRCCS
NOT_YET_RECRUITINGRoma, Roma, 00149, Italy
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Ini-Fiocruz
RECRUITINGRio de Janeiro, Rio de Janerio, 21040-900, Brazil
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Institut de Recherches Cliniques de Montréal (IRCM)
RECRUITINGMontreal, Quebec, H2W 1R7, Canada
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Joint Clinical Research Centre (JCRC)
NOT_YET_RECRUITINGKampala, Kampala, 10005, Uganda
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Laura Rodriguez Research Institute
RECRUITINGSan Diego, California, 92101, United States
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Sapienza Università di Roma
NOT_YET_RECRUITINGRoma, Roma, 00185, Italy
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University Teaching Hospital
NOT_YET_RECRUITINGLusaka, Lusaka Province, 10100, Zambia
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Università degli Studi di Modena e Reggio Emilia
NOT_YET_RECRUITINGModena, 41124, Italy
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Can slow breathing retrain the nervous system to fight long COVID?
- Can a brain zapping headset restore focus after long COVID?
- Mindfulness may offer relief for long COVID sufferers
- Can wearables decode the mystery of fatigue?
- Beetroot juice: a natural boost against long COVID fatigue?
- A One-Two punch for long COVID? supplement and therapy put to the test