Clinical trial NCT05965726: RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid 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-19
Long COVID
Keywords: PASC
Paxlovid
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2023-07-28
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 is an appendix of master protocol (NCT05595369) 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 sub-study is a prospective, multi-center, double-blind, randomized, controlled trial evaluating nirmatrelvir/ritonavir (Paxlovid) in two dosing durations for the treatment of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The study is evaluating 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 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: For this appendix of the master protocol (NCT05595369), participants will be randomized to Paxlovid (nirmatrelvir/ritonavir) vs. ritonavir control plus nirmatrelvir-matching placebo.

When there are multiple study interventions (sub-studies) available under the master protocol (NCT05595369), randomization will occur based on the specific inclusion/exclusion criteria of each appendix.

Eligibility criteria: See NCT NCT05595369 for RECOVER-VITAL: Platform Protocol level exclusion criteria which applies to this appendix

Additional Appendix Level Exclusion Criteria:

1. Known pregnancy\*
2. Active or expected breastfeeding during the study
3. Known eGFR \< 30 mL/min
4. Known severe hepatic impairment (Child-Pugh Class C)
5. Current use of drugs highly dependent on CYP3A for clearance\*\* and for which elevated concentrations are associated with serious and/or life-threatening reactions and which cannot be interrupted during the time of study administration and within seven days before and after study drug administration
6. Current use of potent CYP3A inducers\*\* where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance

   * A pregnancy test must be performed at the Baseline Visit for participants who are capable of becoming pregnant.

     * A guide of drugs that may be contraindicated are listed in Section 4 CONTRAINDICATIONS of the Full Prescribing Information of the EUA for PAXLOVID. https://labeling.pfizer.com/ShowLabeling.aspx?id=16474\&format=pdf

Primary outcomes:
measure: Change in cognitive dysfunction symptom cluster, as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function T-score
timeFrame: Baseline to Day 90
measure: Change in autonomic dysfunction symptom cluster, as measured by the orthostatic hypotension questionnaire (OHQ)
timeFrame: Baseline to Day 90
measure: Change in exercise intolerance symptom cluster, as measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM)
timeFrame: Baseline to Day 90
Secondary outcomes:
measure: Change in cognitive dysfunction symptom cluster, as measured by a neurocognitive battery
timeFrame: Baseline to Day 90
measure: Change in autonomic dysfunction symptom cluster, as measured by the active stand test
timeFrame: Baseline to Day 90
measure: Change in exercise intolerance symptom cluster, as measured by the endurance shuttle walk test (ESWT)
timeFrame: Baseline to Day 90
measure: Occurrence of individual SAEs
timeFrame: Baseline to Day 190
measure: Occurrence of one or more SAEs
timeFrame: Baseline to Day 190
measure: Occurrence of AEs and SAEs leading to discontinuation
timeFrame: Baseline to Day 25
measure: Occurrence of Events of Special Interest (ESIs)
timeFrame: Baseline to Day 190
measure: Adherence in intervention versus control groups as measured by number of missed doses
timeFrame: Baseline to Day 25
Other outcomes:
Locations:
city: Durham
country: United States
facility: All sites listed under NCT05595369
state: North Carolina
Study officials:
References: