Abstract Introduction Limited information is available on the natural history, presentation, and management of pediatric narcolepsy. CATNAP® is a retrospective and prospective, longitudinal, multicenter, web-based pediatric narcolepsy registry (NCT04899947). The primary objectives are to improve understanding of the natural history of pediatric narcolepsy, characterize symptom presentation and diagnosis, and understand treatment practices and outcomes. After registry initiation, an innovative decentralized approach was added to adapt to the post-COVID-19 environment and reach additional participants via social media. Methods Eligible children/adolescents (< 18 years) with confirmed narcolepsy were recruited. Participants, caregivers, and clinicians, leveraging web-based portals, answered questions on sociodemographic characteristics; diagnostic, medical, and treatment history; comorbidities; and disease progression. Participants continue to answer follow-up questions annually until they reach 25 years of age or decline to participate. Since registry initiation in September 2020, 17 sites have been activated, including a virtual site launched in August 2022. Hybrid decentralized recruitment required a new web interface, Institutional Review Board submissions, and 7-week social media campaign (press release, 5 targeted posts) to accompany the virtual site launch. Results A total of 126 participants have been enrolled (signed consent), including 75 participants at 16 physical sites over the first 2 years and 51 participants at the virtual site over 10.6 weeks. Rates of engagement (eg, clicks, likes, and shares) for Instagram (3.2%), LinkedIn (7.2%), and Twitter (2.4%) exceeded “good engagement rate” benchmarks for these platforms. Although the engagement rate for Facebook was below benchmarks (< 2%), the absolute number of “clicks” (29) was the largest among social media platforms in the campaign. Conclusion A hybrid recruitment approach for CATNAP demonstrates incorporation of patient-driven considerations into clinical trial design and increases access to future real-world data registries and studies. Decentralization likely increases enrollment and may enable representation from more diverse regions and populations. This is especially important for rare diseases. The CATNAP Registry provides valuable information on the experience and management of pediatric narcolepsy, which will benefit patients and caregivers, inform clinical decision-making, and potentially contribute to development of new treatments. This successful implementation of a hybrid approach with physical and virtual sites could inform design of future registries. Support (if any) Jazz Pharmaceuticals