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

BACKGROUND

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