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Background: Chronic kidney disease (CKD) is a common, progressive condition. Lifestyle changes and antihypertensive medication can slow the progression to end-stage kidney disease, which requires renal replacement therapy. However, adherence to these recommendations is often low., Objective: The aim of CareKnowDo was to assess the feasibility of rolling out a digital self-management support and adherence program integrated with a patient-facing electronic health record, Patient View (PV)., Methods: A 2-arm, parallel, individual-level pragmatic feasibility pilot randomized controlled trial was conducted at 2 National Health Service (NHS) sites in the United Kingdom. A total of 61 patients with CKD were randomized 1:1 into 2 groups and provided with either a new, tailored digital and telephone support program (CareKnowDo: 31/61, 51%) integrated with PV or standard care (PV alone: 30/61, 49%). Quantitative measures included clinical and psychosocial measures. The primary outcomes were feasibility based: recruitment rate, dropout, and the exploration of associations., Results: Of the 1392 patients screened in local kidney clinics, 269 (19.32%) met the basic inclusion criteria; the first 22.7% (61/269) who met the eligibility criteria were recruited to participate in the study. Of the 69 patients, 23 (38%) patients completed the final 6-month follow-up web-based survey. Reasons for the attrition were explored. A higher belief in the ability of the treatment to control CKD was associated with lower blood pressure at baseline (r=0.52; P=.005), and a higher perceived understanding of CKD at baseline was associated with lower blood pressure at follow-up (r=0.66; P<.001). Beliefs about medicines at baseline were associated with blood pressure at baseline but not at follow-up. This was true for both concerns about medicines (r=0.58; P=.001) and perceived necessity of medicines (r=0.42; P=.03)., Conclusions: A tailored digital and nurse call-based program to enhance support for patients with CKD was piloted in 2 NHS sites and found to be feasible and acceptable. However, to maximize the effectiveness of the intervention (and of future trials), consideration should be given to the target audience most likely to benefit, as well as how to help them access the program as quickly and easily as possible., Trial Registration: NHS Health Research Authority, IRAS ID 184206; https://www.hra.nhs.uk/planning-and-improving -research/application-summaries/research-summaries/careknowdo-pilot-version-1/., (©Riley Elizabeth Reston, Fergus J Caskey, Barnaby Hole, Udaya Udayaraj, John Weinman. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.11.2023.)