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Long COVIDPhase 2RECOVER-VITALNCT05595369

RECOVER-VITAL: Platform Protocol to Measure the Effects of Antiviral Therapies on Long COVID Symptoms

A Phase 2 study testing Experimental: Paxlovid 25 day dosing and Experimental: Paxlovid 15 day dosing in people with Long COVID and Long Covid19, run by Kanecia Obie Zimmerman at 69 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Long COVID, Long Covid19
What is being tested?
Experimental: Paxlovid 25 day dosing and Experimental: Paxlovid 15 day dosing
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
963 participants
Where
69 sitesin 2 countries
Study dates
26 Jul 2023to 13 Mar 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years of age at the time of enrollment
  • Previous suspected, probably or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization*
  • Suspected and probable cases will only be allowed if it occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.
  • Suspected case of SARS-CoV-2 infection - Three options, A through C:
  • A person who meets the clinical OR epidemiological criteria. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or
  • Acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or
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  • With no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.
  • Probable case of SARS-CoV-2 infection:
  • A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.
  • Confirmed case of SARS-CoV-2 infection - Two options, A through B:
  • A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
  • Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
  • At least two moderate symptoms from the same symptom cluster or one severe cluster-associated symptom identified via the Cluster Targeted COVID-19 Symptom Questions (CTCSQ), with participant identifying new symptoms since COVID-19 illness and having persisted for at least 12 weeks
  • Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster
  • Willing and able to provide informed consent, complete the surveys, clinical assessments, and return for all of the necessary follow-up visits

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study. Refer to appendices for additional appendix-level criteria:
  • Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
  • Known severe anemia, defined as < 8 g/dL
  • Meeting the following symptom cluster exclusion for all eligible clusters*:
  • Cognitive dysfunction: known stroke that resulted in cognitive impairment within 3 months of enrollment b. Autonomic dysfunction: atrial fibrillation or significant cardiac arrhythmia, more than moderate alcohol consumption**, pre-existing sustained severe hypertension (BP> 180/110 mmHg in the sitting position) c. Exercise intolerance: i. any of the following within 4 weeks of consent - an acute myocardial infarction or unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, any acute or chronic disorder that may affect exercise performance ii. if the participant is aggravated by exercise (e.g., infection, thyrotoxicosis, unable to cooperate)
  • Participants who are eligible for > 1 cluster must meet all inclusion and no exclusion criteria for an individual symptom cluster. If not, the participant will be excluded from that individual symptom cluster.
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  • Defined as greater than 2 drinks a day for men and 1 drink a day for women. A drink is equivalent to 12 ounces of beer (5% alcohol content), 8 ounces of malt liquor (7% alcohol content), 5 ounces of wine (12% alcohol content), 1.5 ounces or a "shot" of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, whiskey). 21
  • Known diagnosis of chronic Lyme disease with persistent symptoms, sequelae, or related therapy
  • Any non-marijuana illicit drug use within 30 days of informed consent
  • Current or recent use (within the last 14 days) of study intervention*
  • Known allergy/sensitivity or any hypersensitivity to components of the study intervention (s) or control*
  • Known contraindication(s) to study intervention(s),
  • Inability to discontinue symptomatic medications for the identified time periods
  • Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/ special populations/immunocompromised/)
  • Currently enrolled in another clinical trial outside this platform protocol or another study intervention appendix in this platform protocol***
  • Participants may re-enroll in the trial for a different study intervention appendix if the participant has completed an appropriate washout period and efficacy has been determined for the appendix in which the participant was previously enrolled.
  • Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
  • If only one study intervention appendix is open at the time of enrollment. If multiple study intervention appendices are open, a participant may be excluded from any study intervention appendix based on contraindications listed in the study intervention appendix, current use of study intervention, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining study intervention appendices.

Trial locations and contacts

69 sites in 2 countries.

69 sites in 2 countries

United States68 sites

  • University of New Mexico Health Science Center

    Albuquerque, New Mexico, 87106

  • Grady Memorial Hospital

    Atlanta, Georgia, 30303

  • Kaiser Permanente Southwood

    Atlanta, Georgia, 30305

  • Morehouse School of Medicine

    Atlanta, Georgia, 30310

  • Atlanta VA Medical Center

    Atlanta, Georgia, 45267

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35205

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Brigham and Womens Hospital

    Boston, Massachusetts, 02115

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • NYU Langone Health/Brooklyn Hospital

    Brooklyn, New York, 11220

  • St. Lawrence Health Medical Campus

    Canton, New York, 13676

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • University of Virginia

    Charlottesville, Virginia, 22903

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois at Chicago

    Chicago, Illinois, 60612

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • MetroHealth System

    Cleveland, Ohio, 44109

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Vermont Lung Center, University of Vermont

    Colchester, Vermont, 05446

  • Emory Health Care

    Decatur, Georgia, 30030

  • North Shore University Health System

    Evanston, Illinois, 60201

  • Lillestol Research, LLC

    Fargo, North Dakota, 58104

  • Clinical Trials Center of Middle Tennessee

    Franklin, Tennessee, 37067

  • East Carolina University

    Greenville, North Carolina, 27834

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Florida College of Medicine Jacksonville

    Jacksonville, Florida, 32206

  • Duke Clinical and Translational Science Institute

    Kannapolis, North Carolina, 28081

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Lakeland Regional Medical Center

    Lakeland, Florida, 33805

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky Chandler Medical Center

    Lexington, Kentucky, 40536

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Valencia Medical and Research Center

    Miami, Florida, 33165

  • Froedtert Hospital-Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • West Virginia Clinical and Translational Science Institute

    Morgantown, West Virginia, 26506

  • Koch Family Medicine

    Morton, Illinois, 61550

  • Rutgers University-Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08901

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Weil Cornell Medicine

    New York, New York, 10065

  • Hoag Memorial Hospital

    Newport Beach, California, 92663

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Oklahoma Clinical and Translational Science Institute

    Oklahoma City, Oklahoma, 73104

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61603

  • Saint Francis Medical Center

    Peoria, Illinois, 61637

  • University of Arizona/Banner University Medical Center Phoenix

    Phoenix, Arizona, 85006

  • UPMC Presbyterian Shadyside

    Pittsburgh, Pennsylvania, 15213

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • University of California San Francisco General Hospital

    San Francisco, California, 94110

  • Swedish Health Services

    Seattle, Washington, 98104

  • University of Washington

    Seattle, Washington, 98109

  • Jadestone Clinical Research, LLC

    Silver Spring, Maryland, 20904

  • Avera McKennan Hospital & University Health Center

    Sioux Falls, South Dakota, 57108

  • Providence Medical Research Center

    Spokane, Washington, 99204

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • Los Angeles Biomedical Institute at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • University of Arizona Banner Medical Center

    Tucson, Arizona, 85719

  • Howard University Hospital

    Washington D.C., District of Columbia, 20060

  • Wake Forest University

    Winston-Salem, North Carolina, 27103

Other trials in United States

Puerto Rico1 site

  • Hispanic Alliance for Clinical and Translational Research, Univ of Puerto Rico

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: RECOVER-VITAL: A Platform Protocol for Evaluation of Interventions for Viral Persistence, Viral Reactivation, and Immune Dysregulation in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This protocol is a prospective, multi-center, multi-arm, double-blind, randomized, controlled platform trial with different interventions organized as appendices to the protocol. Each appendix (or sub-study) evaluates potential mechanisms of action, efficacy, and safety of antivirals and other therapeutics in individuals with PASC, according to the platform protocol objectives. The hypothesis is that persistent viral infection, viral reactivation, and/or overactive/chronic immune response and inflammation are underlying contributors to PASC and that antiviral and other applicable therapies may result in viral clearance or decreased inflammation and improvement in PASC symptoms.

Read the detailed description

Participants will be randomized to study interventions or placebo/controls based on the arms that are actively enrolling at the time of randomization. Study interventions may be added or removed according to adaptive design and/or emerging evidence. When there are multiple study interventions available, randomization will occur based on appropriateness of each intervention for the participant as determined by the study protocol.

Being tested
Experimental: Paxlovid 25 day dosing, Experimental: Paxlovid 15 day dosing, Placebo Comparator: Control
Keywords
PASC
Medical subject headings
Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Experimental: Paxlovid 25 day dosingDrug

    Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)

  • Experimental: Paxlovid 15 day dosingDrug

    Drug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)

  • Placebo Comparator: ControlDrug

    Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)

Study groups in NCT05595369
Study groupRoleWhat they receive
Experimental: Paxlovid 25 day dosingExperimentalDrug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study)
Receives: Drug: Experimental: Paxlovid 25 day dosing
Experimental: Paxlovid 15 day dosingExperimentalDrug: Paxlovid 15 day Dosing Paxlovid (nirmatrelvir 300mg and ritonavir 100mg) bid x 15 days then ritonavir 100mg bid plus nirmatrelvir matching placebo bid x 10 days See NCT05965726 (Paxlovid Sub-study)
Receives: Drug: Experimental: Paxlovid 15 day dosing
Placebo Comparator: ControlPlacebo comparatorDrug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study)
Receives: Drug: Placebo Comparator: Control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Number of Participants Enrolled in Each Appendix

    Appendix-specific outcome measure data will be reported under the associated NCT ID.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2022
  2. Study start26 Jul 2023
  3. Primary completion6 Aug 2024
  4. Study completion13 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
As part of screening, potential participants will answer symptom questions. Eligible participants will then complete relevant Symptom Cluster assessments at the Screening visit. Participants will subsequently be assigned to one of the three Symptom Clusters based on the assessments. Participants must meet certain criteria within a specific symptom cluster in order to be included in the cluster. After study enrollment and initial cluster assignment, further assessments will be performed. Participants will undergo assessments for the symptom clusters for which the participants qualify.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
963 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05595369
Sponsor's protocol ID
Pro00111697
Other IDs
OTA-21-015G
Acronym
RECOVER-VITAL
Status last verified
Nov 2025
First submitted
11 Oct 2022
Last updated
2 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: The PIs will share the summary of results on the study website: https://recovercovid.org/

Publications

  • Baden LR, Shah NS, Liu STH, Cohen J, Moy J, Kumar A, McComsey GA, Chen P, Floris-Moore M, Singer NG, Fernandez I, Slandzicki AJ, Wiley Z, Kadl A, Kaminsky DA, Hsu H, Walker TA, Hope AA, Ostrosky-Zeichner L, Goldman JD, Peluso MJ, Patterson TF, Parthasarathy S, Mullington JM, Bolin P Jr, Jolley SE, Krishnan JA, Castro M, Hodder SL, Pemu P, Chu HY, Risbano MG, Jerath MR, Mylonakis E, Hurt RT, Alicic R, Azad NS, Sala MA, Harkins MS, Parsonnet J, Stafford N, Robinson P, Hussain S, Qiao X, Hawk ST, Lillestol M, Erdmann N, Gebo KA, Sudhindra P, Sassine J, Marshall GD, Chatterjee T, Morse CG, Kedar E, Stringer WW, Frontera JA, Jordan M, Blaskewicz C, Santana JL, Foot RA, Wongtrakool C, McCarthy MW, Mehari A, Amon A, Cohen AK, Jain N, Maughan C, Lindsay D, Olson R, Broderick S, Rowe P, O'Brien SM, Walt DR, Levy BD, Jason LA, Low PA, Shibao CA, Make B, Bateman L, Redline S, Knopman D, Hernandez AF, Nolen TL, Reist C, Berdan L, Whitley R, Zimmerman KO; RECOVER-VITAL Clinical Trial Group. Nirmatrelvir-ritonavir targeting viral persistence in post-COVID-19 condition (long COVID) in the USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2026 Aug 31:S1473-3099(26)00406-8. doi: 10.1016/S1473-3099(26)00406-8. Online ahead of print.

    PubMed 42673984

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Experimental: Paxlovid 25 day dosing and Experimental: Paxlovid 15 day dosing in people with Long COVID and Long Covid19, run by Kanecia Obie Zimmerman at 69 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 69 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Number of Participants Enrolled in Each Appendix (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05595369, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.

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