RECOVER-VITAL: Platform Protocol to Measure the Effects of Antiviral Therapies on Long COVID Symptoms
Purpose
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.
Conditions
- Long COVID
- Long Covid19
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- ≥ 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- 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
- Masking
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Double blind
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Experimental: Paxlovid 25 day dosing |
Drug: Paxlovid 25 day dosing Paxlovid (nirmatrelvir 300mg, ritonavir 100mg) bid x 25 days See NCT05965726 (Paxlovid Sub-study) |
|
Experimental 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) |
|
Placebo Comparator Placebo Comparator: Control |
Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study) |
|
Recruiting Locations
Birmingham, Alabama 35205
Phoenix, Arizona 85006
Tucson, Arizona 85719
Raymond Skeps
520-626-1590
Los Angeles, California 90048
Newport Beach, California 92663
San Francisco, California 94110
Stanford, California 94305
Kumar
Torrance, California 90502
Aurora, Colorado 80045
Washington, District of Columbia 20060
Jacksonville, Florida 32206
Carmen Isache, MD
Lakeland, Florida 33805
Miami, Florida 33165
Atlanta, Georgia 30303
Atlanta, Georgia 30305
Atlanta, Georgia 30310
Atlanta, Georgia 45267
Decatur, Georgia 30030
Chicago, Illinois 60611
Chicago, Illinois 60612
Chicago, Illinois 60612
Morton, Illinois 61550
Peoria, Illinois 61603
Peoria, Illinois 61637
Kansas City, Kansas 66160
Lexington, Kentucky 40536
Baltimore, Maryland 21287
Silver Spring, Maryland 20904
Boston, Massachusetts 02111
Boston, Massachusetts 02115
Boston, Massachusetts 02118
Boston, Massachusetts 02215
Rochester, Minnesota 55905
Jackson, Mississippi 39216
Saint Louis, Missouri 63110
Lebanon, New Hampshire 03756
New Brunswick, New Jersey 08901
Albuquerque, New Mexico 87106
Brooklyn, New York 11220
Jennifer
Canton, New York 13676
New York, New York 10029
New York, New York 10065
Chapel Hill, North Carolina 27599
Greenville, North Carolina 27834
Kannapolis, North Carolina 28081
Winston-Salem, North Carolina 27103
Fargo, North Dakota 58104
Cincinnati, Ohio 45267
Cleveland, Ohio 44106
Cleveland, Ohio 44109
Cleveland, Ohio 44195
Oklahoma City, Oklahoma 73104
Portland, Oregon 97239
Pittsburgh, Pennsylvania 15213
Sioux Falls, South Dakota 57108
Franklin, Tennessee 37067
Houston, Texas 77030
Houston, Texas 77030
San Antonio, Texas 78229
Colchester, Vermont 05446
David Kaminsky, MD
Charlottesville, Virginia 22903
Norfolk, Virginia 23507
Seattle, Washington 98104
Seattle, Washington 98109
Spokane, Washington 99204
Morgantown, West Virginia 26506
Milwaukee, Wisconsin 53226
San Juan, Puerto Rico 00935
More Details
- NCT ID
- NCT05595369
- Status
- Recruiting
- Sponsor
- Kanecia Obie Zimmerman
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.