Phase 2
N=963
RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms
Long COVID-19 · Long COVID
Bottom Line
View on ClinicalTrials.gov: NCT05965726 ↗Enrolled (actual)
963
Serious AEs
4.4%
Results posted
Mar 2026
Primary outcome: Primary: Percentage of Participants Who Improved in Cognitive Dysfunction Symptom Cluster, as Measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive 8a Function T-score — 57.8; 52.4; 54.6 percentage of participants — p=0.646
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Paxlovid (Drug); Ritonavir (Drug); Nirmatrelvir-matching placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kanecia Obie Zimmerman
- Primary completion
- Dec 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Improved in Cognitive Dysfunction Symptom Cluster, as Measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive 8a Function T-score |
57.8; 52.4; 54.6 | 0.646 |
| PRIMARY Percentage of Participants Who Improved in Autonomic Dysfunction Symptom Cluster, as Measured by the Orthostatic Hypotension Questionnaire (OHQ) |
63.1; 69.4; 69.5 | 0.303 |
| PRIMARY Percentage of Participants Who Improved in Exercise Intolerance Symptom Cluster, as Measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) |
25.5; 34.2; 33.3 | 0.186 |
| SECONDARY Percentage of Participants Who Improved in Cognitive Dysfunction Symptom Cluster, as Measured by a Neurocognitive Battery |
9.8; 8.4; 14.3 | 0.317 |
| SECONDARY Percentage of Participants Who Improved in Autonomic Dysfunction Symptom Cluster, as Measured by the Active Stand Test |
11.8; 15.0; 15.4 | 0.412 |
| SECONDARY Percentage of Participants Who Improved in Exercise Intolerance Symptom Cluster, as Measured by the Endurance Shuttle Walk Test (ESWT) |
16.7; 25.6; 30.6 | 0.014 sig |
| SECONDARY Total Number of SAEs (Serious Adverse Events) |
17; 16; 19 | — |
| SECONDARY Number of Participants Experiencing One or More SAEs (Serious Adverse Events) |
13; 13; 16 | — |
| SECONDARY Number of Participants Experiencing AEs (Adverse Events) or SAEs (Serious Adverse Events) Leading to Treatment Discontinuation |
11; 19; 13 | — |
| SECONDARY Number of Participants With an Event of Special Interest (ESI) |
2; 3; 4 | — |
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.
Eligibility Criteria
See NCT NCT05595369 for RECOVER-VITAL: Platform Protocol level exclusion criteria which applies to this appendix
Additional Appendix Level Exclusion Criteria:
- Known pregnancy*
- Active or expected breastfeeding during the study
- Known eGFR < 30 mL/min
- Known severe hepatic impairment (Child-Pugh Class C)
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT05965726). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.