Phase 2 trial of Paxlovid for Long COVID cognitive, autonomic, and exercise symptoms completed.

Status: COMPLETED | Phase: PHASE2 Condition(s): Long COVID-19, Long COVID Intervention(s): Paxlovid (DRUG), Ritonavir (DRUG), Nirmatrelvir-matching placebo (DRUG) 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: 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. Primary Outcome(s): 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; Percentage of Participants Who Improved in Autonomic Dysfunction Symptom Cluster, as Measured by the Orthostatic Hypotension Questionnaire (OHQ); Percentage of Participants Who Improved in Exercise Intolerance Symptom Cluster, as Measured by the Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM) Enrollment: 964 (ACTUAL) Lead Sponsor: Kanecia Obie Zimmerman Start: 2023-07-26 | Primary Completion: 2024-12-05 Results posted: 2026-03-27