Clinical trial NCT05595369: RECOVER-VITAL: Platform Protocol to Measure the Effects of Antiviral Therapies on Long COVID Symptoms
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Long COVID
Long Covid19
Keywords: PASC
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2022-10-27
Enrollment: 964
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Total number of participants enrolled in each Appendix
timeFrame: 90 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: University of Arizona/Banner University Medical Center Phoenix
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Banner Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco General Hospital
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Institute at Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Medical Center
state: Florida
city: Miami
country: United States
facility: Valencia Medical and Research Center
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Kaiser Permanente Southwood
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Decatur
country: United States
facility: Emory Health Care
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: Morton
country: United States
facility: Koch Family Medicine
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Saint Francis Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Silver Spring
country: United States
facility: Jadestone Clinical Research, LLC
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Rutgers University-Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Health Science Center
state: New Mexico
city: Brooklyn
country: United States
facility: NYU Langone Health/Brooklyn Hospital
state: New York
city: Canton
country: United States
facility: St. Lawrence Health Medical Campus
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weil Cornell Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Kannapolis
country: United States
facility: Duke Clinical and Translational Science Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research, LLC
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth System
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical and Translational Science Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Shadyside
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital & University Health Center
state: South Dakota
city: Franklin
country: United States
facility: Clinical Trials Center of Middle Tennessee
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Colchester
country: United States
facility: Vermont Lung Center, University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Swedish Health Services
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Providence Medical Research Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia Clinical and Translational Science Institute
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital-Medical College of Wisconsin
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: Hispanic Alliance for Clinical and Translational Research, Univ of Puerto Rico
Study officials:
affiliation: Duke University
name: Kanecia Zimmerman, MD PhD
role: STUDY_CHAIR
affiliation: University of Alabama at Birmingham Medical Center
name: Richard Whitley, MD
role: STUDY_CHAIR
References: