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)
Brief Summary

This study is a platform protocol designed to be flexible so that it is suitable for awide range of settings within health care systems and in community settings where it canbe integrated into COVID-19 programs and subsequent treatment plans. This protocol is aprospective, multi-center, multi-arm, double-blind, randomized, controlled platform trialwith different interventions organized as appendices to the protocol. Each appendix (orsub-study) evaluates potential mechanisms of action, efficacy, and safety of antiviralsand other therapeutics in individuals with PASC, according to the platform protocolobjectives. The hypothesis is that persistent viral infection, viral reactivation, and/oroveractive/chronic immune response and inflammation are underlying contributors to PASCand that antiviral and other applicable therapies may result in viral clearance ordecreased 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.

Active, not recruiting
Long Covid
Long Covid19

Drug: Experimental: Paxlovid 25 day dosing

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

Drug: Experimental: Paxlovid 15 day dosing

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)

Drug: Placebo Comparator: Control

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

Eligibility Criteria

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

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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
Puerto Rico
United States
Locations

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

Kanecia Obie Zimmerman
NCT Number
Keywords
PASC
MeSH Terms
Post-Acute COVID-19 Syndrome
Nirmatrelvir and ritonavir drug combination