Bioavailability and Practicability of Envarsus Versus Advagraf in Liver Transplant Recipients

Summary

Trial participants are randomised within 14 days after liver transplantation surgery in a 1:1 ratio to two alternative treatment arms containing either Envarsus® (test arm) or Advagraf® (comparator arm) as first-line calcineurin inhibitor within a standard-of-care immunosuppressive regimen. Tacrolimus blood trough levels and drug doses are monitored at regular intervals to assess drug bioavailability and the ease and accuracy of achieving the targeted blood concentration range. Dose-normalised trough level (concentration/dose ratio) is measured at 12 weeks post-randomisation as an estimate of tacrolimus bioavailability. It is hypothesised that treatment with Envarsus® will confer a superior (higher) C/D ratio after 12 weeks of therapy owing to the superior bioavailability of this galenic drug formulation (proprietary MeltDose® technology). To test whether an elevated C/D ratio is also associated with improved clinical outcomes, a range of other pharmacokinetic, efficacy and safety variables are evaluated at 10 study visits spanning a period of 3 years.

Timeline

Start

2020-12-23

Primary completion

2024-01-25

Completion

2026-10

Publications

• Wohl DS, James B, Gotz M, Brennfleck F, Holub-Hayles I, Mutzbauer I, Baccar S, Brunner SM, Geissler EK, Schlitt HJ; EnGraft Trial Group. EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus(R) versus Advagraf in liver transplant recipients. Trials. 2023 May 11;24(1):325. doi: 10.1186/s13063-023-07344-7.

Drugs

Indications

No indication recorded.