Development and Use of a Digital DDI Screening Tool in STRIVE Ensitrelvir COVID-19 Trial

Overview

A digital drug–drug interaction (DDI) screening tool was developed and implemented for the STRIVE trial evaluating ensitrelvir in hospitalized COVID-19 patients. The tool facilitated safe medication management by categorizing over 1100 medications and providing guidance on prohibited, permitted, and conditionally permitted drugs, with extensive use across 150 sites in 13 countries.

Background

Ensitrelvir is an oral antiviral targeting SARS-CoV-2 with significant DDI potential due to inhibition of CYP3A, P-glycoprotein, BCRP, and OAT-3. Hospitalized COVID-19 patients often receive multiple concomitant medications, complicating ensitrelvir use. Unlike other antivirals, ensitrelvir has a longer half-life, extending DDI risk post-treatment. Prior to STRIVE, no dedicated DDI resources for ensitrelvir existed, necessitating development of a specialized screening tool to ensure trial safety and integrity.

Data Highlights

Key Findings

• The DDI screener was developed by a multidisciplinary team and launched in December 2022, expanding from 615 to 1182 medications over 7 versions.
• Medications were categorized as permitted, prohibited, or conditionally permitted with washout and restart guidance provided.
• Eleven prohibited medications were reclassified as conditionally permitted after dosage adjustments, including antihypertensives, anti-infectives, and psychiatric drugs.
• Anticoagulants, immunosuppressants, and emergency use medications posed the greatest challenges due to trial blinding and safety concerns.
• Over 117,000 searches were performed by 150 sites, with the tool most valued during screening/enrollment and for washout guidance.
• The iterative development process incorporated real-time feedback from trial sites to optimize usability and safety.

Clinical Implications

The digital DDI screening tool enabled safe and efficient management of complex medication regimens in hospitalized COVID-19 patients receiving ensitrelvir. Its use highlights the importance of dedicated, dynamic DDI resources in clinical trials involving investigational drugs with high interaction potential. Multidisciplinary collaboration and ongoing site feedback are critical for successful implementation and patient safety.

Conclusion

The STRIVE ensitrelvir trial’s digital DDI screener represents a vital resource facilitating safe concomitant medication use in a complex hospitalized population. This model underscores the necessity of tailored DDI management tools in clinical trials of novel therapeutics with significant interaction risks.

References

1. STRIVE Trial Team 2024 -- Development and Use of a Digital Drug-Drug Interaction Screening Tool for the STRIVE Trial of Ensitrelvir in COVID-19 Treatment