• Harlan M Krumholz, Mitsuaki Sawano, Bornali Bhattacharjee, César Caraballo, Rohan Khera, Shu-Xia Li, Jeph Herrin, Andreas Coppi, Julie Holub, Yashira Henriquez, Maria A Johnson, Theresa B Goddard, Erica Rocco, Amy C Hummel, Al MouslmaniMohammadMYale School of Medicine, New Haven, CT., David F Putrino, Kevin D Carr, Santos Carvajal-Gonzalez, Lawrence Charnas, Magdia De Jesus, Frank W Ziegler, and Akiko Iwasaki.
• Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT; Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT; Department of Health Policy and Management, Yale School of Public Health, New Haven, CT; Center for Infection and Immunity, Yale School of Medicine, New Haven, CT. Electronic address: harlan.krumholz@yale.edu.
• Am. J. Med. 2024 May 10.

BackgroundIndividuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID.MethodsThe PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders.ConclusionThe PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.Copyright © 2024. Published by Elsevier Inc.

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