Implementation of an Online Drug–Drug Interaction Screener for the STRIVE Ensitrelvir Trial for COVID-19
Year: 2025
Type: article
Abstract: Background: -gp), breast cancer resistance protein (BCRP), and organic anion transporter-3 (OAT-3) inhibition. We present the development and implementation of an online DDI screener to assess interactions during the STRIVE ensitrelvir trial. Methods: The STRIVE Network is conducting a randomized, double-blind, placebo-controlled trial evaluating ensitrelvir's efficacy and safety in hospitalized adults with coronavirus disease 2019 (COVID-19) and lower respiratory tract involvement. DDI guidance was compiled into a database accessed via a web portal where a multidisciplinary team categorized medications as permitted, prohibited, or conditionally permitted. For prohibited medications, washout periods and start/restart criteria were provided with alternative medication suggestions. Sites could request new medications for addition. After 18 months, a survey was conducted to assess the tool's usefulness. Results: Version 1 of the DDI screener launched in December 2022 with 615 medications, expanding to 1182 through 6 updates by version 7. In 11 cases, prohibited medications were revised to conditionally permit enrollment after dosage adjustments (antihypertensives, anti-infectives, and psychiatric medications). Anticoagulants, immunosuppressants, and emergency use medications posed the greatest challenges due to trial blinding. With 334 participants enrolled across 150 sites in 13 countries, 117192 screener searches were completed by May 2024. The most searched medication classes were antihypertensive, antibiotics, corticosteroids, and anticoagulants. Sites found the DDI screener most helpful during screening/enrollment and valued the washout guidance. Conclusions: DDI resources for investigational medications like ensitrelvir, with high DDI potential, are crucial for safe conduct of clinical trials. Effective implementation requires a multidisciplinary, iterative approach that incorporates real-time feedback from trial sites.
Source: Open Forum Infectious Diseases
DOI: 10.1093/ofid/ofaf327
Authors: Joshua P Havens, Nayon Kang, Lucy Chung, Courtney V Fletcher, Page Crew, Jacqueline Nordwall, Lianne Siegel, Katrina Harper, Birgit Grund, Marcelo Losso, Shikha Vasudeva, Kyle C Molina, Adit A Ginde, Ryosuke Shimizu, Ahmad Mourad, Alpha Diallo, Mina Pak, Anne Davis-Karim, Phiona Nabaggala, Alfredo J Mena Lora, Derek W Russell, Sho Saito, Jason V Baker
Institutions: University of Nebraska Medical Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, University of Minnesota, Hospital Ramos Mejía, Veterans Health Administration, Salem VA Medical Center, University of Colorado Anschutz, University of Colorado Denver, Shionogi (Japan), Duke University, Duke Medical Center, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, The University of Texas Southwestern Medical Center, New Mexico VA Health Care System, MRC/UVRI & LSHTM Uganda Research Unit, Medical Research Council, Uganda Virus Research Institute, University of Illinois Chicago, University of Alabama at Birmingham, Birmingham VA Medical Center, UAB Medicine, National Center for Global Health and Medicine
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
OpenAlex ID: W4411209544