Design and rationale of RECOVER-AUTONOMIC: a randomized platform trial evaluating interventions for Long COVID postural orthostatic tachycardia syndrome
Fudim, M; Novak, P; Taub, PR; et al., American Heart Journal, February 2026
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Publication Details
DOI: 10.1016/j.ahj.2026.107384
Abstract
Background: Post‑acute sequelae of SARS‑CoV‑2 infection (Long COVID) affect a substantial proportion of individuals, and among the many reported symptom clusters, autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), represents an important subset. The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative developed by the National Institutes of Health included a platform trial (RECOVER-AUTONOMIC) designed to assess the safety, tolerability, and efficacy of three interventions — (1) coordinated nonpharmacologic care, (2) pharmacotherapy with intravenous immunoglobulin (IVIG), and (3) pharmacotherapy with ivabradine — in treating POTS in adults with Long COVID.
Methods: RECOVER-AUTONOMIC is a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. Participants are randomized to IVIG or ivabradine with matching placebo, and (in a factorial design) to either coordinated nonpharmacologic care or usual care. The primary endpoint is the change in orthostatic intolerance symptoms measured by the Orthostatic Hypotension Questionnaire/Orthostatic Intolerance Questionnaire from baseline to the end of intervention. Secondary endpoints include quality of life, functional performance, symptom burden, and safety. Exploratory endpoints include autonomic function testing, wearable sensor data, and longitudinal biomarker profiling.
Discussion: RECOVER-AUTONOMIC seeks to determine the benefits and risks of IVIG and of ivabradine, as well as of coordinated nonpharmacologic care, for the treatment of POTS in Long COVID. Results from this trial will offer the largest source of evidence to help guide the medical care of this population.
Trial registration: ClinicalTrials.gov - Platform: NCT06305780; Appendix A (intravenous immunoglobulin): NCT06305793; Appendix B (ivabradine): NCT06305806. Protocol available at https://trials.recovercovid.org/autonomic.
Authors
Marat Fudim, Peter Novak, Pam R Taub, Tae Chung, Kanecia O Zimmerman, Orsolya V Moy, Hirra Zahir Fissler, Jun Wen, Nikki L B Freeman, Sean O'Brien, Heather Marti, Dane Cook, Philip Low, Dong-Yun Kim, Yves Rosenberg, Christopher B Granger, Cyndya A Shibao
Keywords
COVID-19; Long COVID; PASC; RECOVER-AUTONOMIC; dysautonomia; intravenous immunoglobulin; ivabradine; pharmacologic and nonpharmacologic interventions; platform protocol; postural orthostatic tachycardia syndrome