RECOVER-VITAL

Currently Recruiting: Participants

Study Drug/Intervention: PAXLOVID 25d vs. PAXLOVID 10d vs. placebo+ritonavir

Study Timeline: This study is expected to conclude enrollment in December 2024.

Visit the Study Website

ClinicalTrials.gov ID: NCT05965726

Objectives

Primary: Evaluate the effect of intervention(s) versus control on symptom-specific patient-reported outcome measures within each PASC symptom cluster at Day 90

Secondary:

1. Evaluate the effect of intervention(s) versus control on performance-based outcomes within each PASC symptom cluster
2. Characterize the safety and tolerability of intervention(s) in PASC

Exploratory:

1. Investigate mechanisms of potential intervention (s) efficacy
2. Compare the effect of intervention(s) on symptom burden and health related quality of life (HRQOL) versus control
3. Evaluate the durability of intervention(s) response
4. Evaluate intervention(s) effect on healthcare utilization
5. Describe the effect of intervention(s) versus control across exploratory performance-based outcomes and patient reported outcomes (PROs) within each PASC symptom cluster
6. Determine biomarkers associated with PASC symptom clusters and intervention-associated recovery

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

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

1. Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization^18ɸ

^ɸ Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required. Refer to the MOP for details.

Suspected case of SARS-CoV-2 infection – Three options, A through C:

1. 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
2. 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
3. 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:

1. 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:

1. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
2. 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.

1. 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), see Section 8.10.3, with participant identifying new symptoms since COVID-19 illness and having persisted for at least 12 weeks¹⁹
2. Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster (See Section 8.10.4)
3. 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/dL²⁰
3. Meeting the following symptom cluster exclusion for all eligible clusters^#:
4. Cognitive dysfunction: known stroke that resulted in cognitive impairment within 3 months of enrollment
5. Autonomic dysfunction: atrial fibrillation or significant cardiac arrhythmia, more than moderate alcohol consumption^ɣ, pre-existing sustained severe hypertension (BP> 180/110 mmHg in the sitting position)
6. Exercise intolerance:
7. 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
8. if they are 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, they will be excluded from that individual symptom cluster.

^ɣ 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

1. Known diagnosis of Lyme disease
2. Any non-marijuana illicit drug use within 30 days of informed consent
3. Current or recent use (within the last 14 days) of study intervention*
4. Known allergy/sensitivity or any hypersensitivity to components of the study intervention (s) or control*
5. Known contraindication(s) to study intervention(s),
6. Inability to discontinue symptomatic medications for the identified time periods (See Section 6.5.1)
7. Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines
8. Enrolled into another study intervention appendix in this platform protocol^$

^$Participants may re-enroll in the trial for a different study intervention appendix if they have completed an appropriate washout period and efficacy has been determined for the appendix in which they were previously enrolled.

1. 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 interventionappendix 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.

National Institutes of Health

• PI: Kanecia Zimmerman, MD, MPH
• PL: Rachel Olson, Annie Pennella