RECOVER-VITAL: Platform Protocol to Measure the Effects of Antiviral Therapies on Long COVID Symptoms (RECOVER-VITAL)
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| ClinicalTrials.gov Identifier: NCT05595369 |
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Recruitment Status :
Enrolling by invitation
First Posted : October 27, 2022
Last Update Posted : May 6, 2024
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| Condition or disease | Intervention/treatment | Phase |
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| Long COVID Long Covid19 | Drug: Experimental: Paxlovid 25 day dosing Drug: Experimental: Paxlovid 15 day dosing Drug: Placebo Comparator: Control | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 900 participants |
| 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. |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Masking Description: | Double blind |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | July 26, 2023 |
| Estimated Primary Completion Date : | July 2025 |
| Estimated Study Completion Date : | October 2025 |
| Arm | Intervention/treatment |
|---|---|
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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)
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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) |
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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)
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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) |
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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)
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Drug: Placebo Comparator: Control
Drug: Control ritonavir 100mg taken bid plus nirmatrelvir matching placebo bid bid x 25 days See NCT05965726 (Paxlovid Sub-study) |
- Change in Cognitive dysfunction symptom cluster, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function T-score [ Time Frame: Baseline to Day 90 ]The PROMIS cognitive function-8a (PRO assessment) T-score is a quantitative measure of current cognitive function. The primary endpoint for cognitive dysfunction is improvement of at least 5 T-score points on the PROMIS-cognitive function as measured at 90 days compared to baseline.
- Change in Autonomic dysfunction symptom cluster, as measured by the orthostatic hypotension questionnaire (OHQ) [ Time Frame: Baseline to Day 90 ]The OHQ [Orthostatic Hypotension Questionnaire [PRO assessment)] is a measure of orthostatic intolerance, which has been the primary presentation of patients with PASC-related autonomic dysfunction. This measure includes the Orthostatic Intolerance Daily Activity Scale (OIDAS) and the Orthostatic Intolerance Symptom Assessment (OISA). The primary endpoint for autonomic dysfunction is improvement in autonomic function as defined by a ≥ 1-point decrease in the OHQ question 1 at 90 days compared to baseline.
- Change in Exercise intolerance symptom cluster, as measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) [ Time Frame: Baseline to Day 90 ]DSQ-PEM assesses symptom frequency and severity over a 6-month look back period, however, for the purposes of this study, it will be modified to assess over a 1-week look back period. Frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time. Severity is also rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. For exercise intolerance, the primary endpoint is improvement in PEM, defined as having no symptoms of moderate or greater severity with 50% or more frequency as determined by the DSQ-PEM short form at day 90.
- Change in Cognitive dysfunction symptom cluster, as measured by a neurocognitive battery [ Time Frame: Baseline to Day 90 ]The neurocognitive battery outcome is a binary indicator of whether the participant has evidence of deficits (at least one standard deviation below the mean on at least one test within the battery).
- Change in Autonomic dysfunction symptom cluster, as measured by the Active stand test [ Time Frame: Baseline to Day 90 ]The active stand test outcome is a binary indicator of whether the follow-up active stand test result was abnormal or normal.
- Change in Exercise intolerance symptom cluster, as measured by the endurance shuttle walk test (ESWT) [ Time Frame: Baseline to Day 90 ]The ESWT [Endurance shuttle walk test (performance measure)] consists of timed walking on a 10m course.The ESWT will primarily be analyzed as a binary endpoint defined as an increase of at least 3 minutes of walking time at follow-up compared to baseline.
- Occurrence of individual SAEs [ Time Frame: Baseline to Day 90 ]
- Occurrence of AEs and SAEs leading to discontinuation [ Time Frame: Baseline to Day 90 ]
- Occurrence of Events of Special Interest (ESIs) [ Time Frame: Baseline to Day 90 ]
- Duration of ESIs [ Time Frame: Baseline to Day 90 ]
- Adherence in intervention versus control groups as measured by number of missed doses [ Time Frame: Baseline to Day 90 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- ≥ 18 years of age at the time of enrollment
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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.
- 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
- Meeting PRO Symptom Cluster criteria for at least one Symptom Cluster
- 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:
- Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
- Known severe anemia, defined as < 8 g/dL
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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
- Known diagnosis of chronic Lyme disease with persistent symptoms, sequelae, or related therapy
- Any non-marijuana illicit drug use within 30 days of informed consent
- Current or recent use (within the last 14 days) of study intervention*
- Known allergy/sensitivity or any hypersensitivity to components of the study intervention (s) or control*
- Known contraindication(s) to study intervention(s),
- Inability to discontinue symptomatic medications for the identified time periods
- Moderate or severe immunocompromised patients, such as those described in the NIH COVID-19 Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/ special populations/immunocompromised/)
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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.
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05595369
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| Study Chair: | Kanecia Zimmerman, MD PhD | Duke University | |
| Study Chair: | Richard Whitley, MD | University of Alabama at Birmingham Medical Center |
| Responsible Party: | Kanecia Obie Zimmerman, Associate Professor of Pediatrics, Duke University |
| ClinicalTrials.gov Identifier: | NCT05595369 |
| Other Study ID Numbers: |
Pro00111697 OTA-21-015G ( Other Grant/Funding Number: NIH grant to RTI; RTI subcontracting with DCRI ) |
| First Posted: | October 27, 2022 Key Record Dates |
| Last Update Posted: | May 6, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | The PIs will share the summary of results on the study website: https://recovercovid.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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PASC |
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Post-Acute COVID-19 Syndrome COVID-19 Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections |
RNA Virus Infections Lung Diseases Respiratory Tract Diseases Post-Infectious Disorders Chronic Disease Disease Attributes Pathologic Processes Nirmatrelvir and ritonavir drug combination Antiviral Agents Anti-Infective Agents |