Development of a Multicomponent Implementation Strategy to Reduce Upper Gastrointestinal Bleeding Risk in Patients Using Warfarin and Antiplatelet Therapy, and Protocol for a Pragmatic Multilevel Randomized Factorial Pilot Implementation Trial
Authors: Kurlander Jacob , Helminski Danielle , Lanham Michael , Henstock Jennifer L , Kidwell Kelley M , Krein Sarah L , Saini Sameer D , Richardson Caroline R , De Vries Raymond , Resnicow Kenneth , Ruff Allison LaBoon , Wallace David M , Jones Elizabeth K , Perry Linda K , Parsons Jacqueline , Ha Nghi , Alexandris-Souphis Tina , Dedrick Dale , Aldridge Elizabeth , Barnes Geoffrey D 
Published: December 2021

Abstract
BackgroundConcomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe 1) the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS) and 2) the design of a pilot pragmatic implementation trial.MethodsA participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) Clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: The nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review.DiscussionThis pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase use of best practices for upper GI bleeding risk reduction.Trial RegistrationClinicalTrials.gov, NCT05085405, Registered 19 October 2021 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05085405