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

Phase 2

Active, not recruiting

• Conditions: Long Covid19; Long COVID

• Registration Number: NCT05595369
• Lead Sponsor: Kanecia Obie Zimmerman

Brief 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. 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.

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2022-10-11
• Study First Submitted QC: 2022-10-24
• Study First Posted: 2022-10-27
• Study Start: 2023-07-26
• Primary Completion: 2024-08-06
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-15
• Last Update Posted: 2024-10-17
• Study Completion: 2025-03-14

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

1. ≥ 18 years of age at the time of enrollment

2. 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. 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

   B. 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

   C. 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. 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. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or

   B. 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.

3. 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

4. Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster

5. Willing and able to provide informed consent, complete the surveys, clinical assessments, and return for all of the necessary follow-up visits

Read More

Exclusion Criteria

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:

1. Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent

2. Known severe anemia, defined as < 8 g/dL

3. Meeting the following symptom cluster exclusion for all eligible clusters*:

   a. 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.

   ** 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

4. Known diagnosis of chronic Lyme disease with persistent symptoms, sequelae, or related therapy

5. Any non-marijuana illicit drug use within 30 days of informed consent

6. Current or recent use (within the last 14 days) of study intervention*

7. Known allergy/sensitivity or any hypersensitivity to components of the study intervention (s) or control*

8. Known contraindication(s) to study intervention(s),

9. Inability to discontinue symptomatic medications for the identified time periods

10. Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/ special populations/immunocompromised/)

11. 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.

12. 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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Total number of participants enrolled in each Appendix	90 Days	Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#

Trial Locations

Locations (69)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arizona/Banner University Medical Center Phoenix; 🇺🇸 Phoenix, Arizona, United States

University of Arizona Banner Medical Center; 🇺🇸 Tucson, Arizona, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Hoag Memorial Hospital; 🇺🇸 Newport Beach, California, United States

University of California San Francisco General Hospital; 🇺🇸 San Francisco, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

Los Angeles Biomedical Institute at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Howard University Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Florida College of Medicine Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Lakeland Regional Medical Center; 🇺🇸 Lakeland, Florida, United States

Valencia Medical and Research Center; 🇺🇸 Miami, Florida, United States

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

Kaiser Permanente Southwood; 🇺🇸 Atlanta, Georgia, United States

Morehouse School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Atlanta VA Medical Center; 🇺🇸 Atlanta, Georgia, United States

Emory Health Care; 🇺🇸 Decatur, Georgia, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

North Shore University Health System; 🇺🇸 Evanston, Illinois, United States

Koch Family Medicine; 🇺🇸 Morton, Illinois, United States

Methodist Medical Center of Illinois; 🇺🇸 Peoria, Illinois, United States

Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Kentucky Chandler Medical Center; 🇺🇸 Lexington, Kentucky, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Jadestone Clinical Research, LLC; 🇺🇸 Silver Spring, Maryland, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Brigham and Womens Hospital; 🇺🇸 Boston, Massachusetts, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Dartmouth Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States

Rutgers University-Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States

University of New Mexico Health Science Center; 🇺🇸 Albuquerque, New Mexico, United States

NYU Langone Health/Brooklyn Hospital; 🇺🇸 Brooklyn, New York, United States

St. Lawrence Health Medical Campus; 🇺🇸 Canton, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Weil Cornell Medicine; 🇺🇸 New York, New York, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Duke Clinical and Translational Science Institute; 🇺🇸 Kannapolis, North Carolina, United States

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

Lillestol Research, LLC; 🇺🇸 Fargo, North Dakota, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

MetroHealth System; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Oklahoma Clinical and Translational Science Institute; 🇺🇸 Oklahoma City, Oklahoma, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

UPMC Presbyterian Shadyside; 🇺🇸 Pittsburgh, Pennsylvania, United States

Avera McKennan Hospital & University Health Center; 🇺🇸 Sioux Falls, South Dakota, United States

Clinical Trials Center of Middle Tennessee; 🇺🇸 Franklin, Tennessee, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Vermont Lung Center, University of Vermont; 🇺🇸 Colchester, Vermont, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Sentara Norfolk General Hospital; 🇺🇸 Norfolk, Virginia, United States

Swedish Health Services; 🇺🇸 Seattle, Washington, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Providence Medical Research Center; 🇺🇸 Spokane, Washington, United States

West Virginia Clinical and Translational Science Institute; 🇺🇸 Morgantown, West Virginia, United States

Froedtert Hospital-Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Hispanic Alliance for Clinical and Translational Research, Univ of Puerto Rico; 🇵🇷 San Juan, Puerto Rico