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Clinical Trial
. 2025 Jun 11;12(7):ofaf327.
doi: 10.1093/ofid/ofaf327. eCollection 2025 Jul.

Implementation of an Online Drug-Drug Interaction Screener for the STRIVE Ensitrelvir Trial for COVID-19

Joshua P Havens  1 , Nayon Kang  2 , Lucy Chung  3 , Courtney V Fletcher  4 , Page Crew  5 , Jacqueline Nordwall  6 , Lianne Siegel  6 , Katrina Harper  6 , Birgit Grund  7 , Marcelo Losso  8 , Shikha Vasudeva  9 , Kyle C Molina  10 , Adit A Ginde  10 , Ryosuke Shimizu  11 , Ahmad Mourad  12   13 , Alpha Diallo  14 , Mina Pak  15 , Anne Davis-Karim  16 , Phiona Nabaggala  17 , Alfredo J Mena Lora  18 , Derek W Russell  19   20 , Sho Saito  21 , Jason V Baker  22
Affiliations
Clinical Trial

Implementation of an Online Drug-Drug Interaction Screener for the STRIVE Ensitrelvir Trial for COVID-19

Joshua P Havens et al. Open Forum Infect Dis. .

Abstract

Background: Ensitrelvir is an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with associated drug-drug interactions (DDIs) through CYP3A, P-glycoprotein (P-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.

Keywords: COVID-19; clinical trial; drug–drug interaction; ensitrelvir; online trial resource.

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Conflict of interest statement

Potential conflicts of interest. J.P.H. reports research grants paid to his institution, the University of Nebraska Medical Center, and consultancy services to ViiV Healthcare, Inc., and Medscape. S.S. received a research grant from Shionogi. K.C.M. served as a consultant for Shionogi. R.S. is an employee of Shionogi. All other authors have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Total medications in the STRIVE DDI screener by version and screener category. Screener category proportions are noted for each version. aDosage adjustments include dosage reduction or use of maximum thresholds. Abbreviations: DDI, drug–drug interaction; STRIVE, Strategies and Treatments of Respiratory Infections and Viral Treatments.
Figure 2.
Figure 2.
Top 25 medication searches in STRIVE DDI screener by drug name. aDosage adjustments include reduction or use of maximum thresholds. Abbreviations: DDI, drug–drug interaction; STRIVE, Strategies and Treatments of Respiratory Infections and Viral Treatments.
Figure 3.
Figure 3.
STRIVE trial site perspectives on helpfulness of DDI screener. Abbreviations: DDI, drug–drug interaction; STRIVE, Strategies and Treatments of Respiratory Infections and Viral Treatments.
Figure 4.
Figure 4.
STRIVE trial site frequency of use of trial DDI materials. Abbreviations: DDI, drug–drug interaction; ESV, ensitrelvir; STRIVE, Strategies and Treatments of Respiratory Infections and Viral Treatments.
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