An Interim Report on a Prospective Randomized Trial of Extended-Release Tacrolimus in Liver Transplantation with Anti-Thymocyte Induction in a Steroid Free Protocol
James D. Eason Transplant Institute at Methodist University Hospital and University of Tennessee Health Science Center, Memphis, TN
Meeting: 2022 American Transplant Congress
Abstract number: 1087
Keywords: Adverse effects, FK506, Immunosuppression, Liver transplantation
Topic: Clinical Science » Liver » 54 - Liver: Immunosuppression and Rejection
Session Information
Session Name: Liver: Immunosuppression and Rejection
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Our study hypothesis was that once daily dosing of extended-release tacrolimus (ERT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT).
*Methods: All liver transplant recipients at our center were screened at transplant. Exclusion criteria included prior transplant or use of calcineurin inhibitor (CNI), dialysis the week before or after transplant, or receipt of a simultaneous liver kidney (SLK), split liver, or living donor graft. Patients with a serum creatinine (SCr) ≤ 2.0 mg/dL between post-operative day (POD) 3 and 7 were randomized to ERT daily (Envarsus XR) or IRT BID. Induction was with rabbit anti-thymocyte globulin (RATG) at transplant and POD 2. Maintenance included mycophenolate for 6 months. Steroids were given only for biopsy proven rejection. Analysis was performed on an intention to treat basis and we utilized SAS version 9.4 software (SAS Institute; Cary, NC) and R programming language for data pre-processing and analyses.
*Results: We screened 194 consecutive patients and enrolled 110. Reasons for exclusion were hemodialysis before or after transplant (38), SLK recipient (14), prior transplant (14), prior CNI use (14), and high SCr (13). Our control and study arms were well matched (Table 1). “Other” cause of liver disease included Alpha 1 disease, hepatic AV malformations, and Neuroendocrine tumor. At all timepoints, both arms had similar SCr and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation. Tacrolimus trough levels were similar between arms. The ERT arm had fewer AEs and fewer serious AEs (Table 2). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not significant, ERT was held temporarily or discontinued less than IRT (Table 2) and had fewer instances of rejection.
*Conclusions: This interim analysis showed that ERT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.
| IR Tac | ER Tac | p-value | |
| Age mean (n) | 57.5(50) | 57.3(50) | 0.92 |
| Caucasian n (%) | 42(47.2) | 47(52.8) | 0.22 |
| African American n (%) | 11(61.1) | 7(38.9) | 0.30 |
| Alcohol n (%) | 14(38.9) | 22(61.1) | 0.10 |
| Hepatitis C n (%) | 9(42.9) | 12(57.1) | 0.46 |
| NASH n (%) | 22(56.4) | 17(43.6) | 0.32 |
| Other n (%) | 0(0) | 5(100) | 0.02 |
| IR Tac | ER Tac | p-value | |
| 2 week eGFR mean (n) | 96.01(54) | 103.82(52) | 0.418 |
| 4 week eGFR mean (n) | 67.61(54) | 66.85(52) | 0.92 |
| 3 month eGFR mean (n) | 74.05(51) | 71.6(52) | 0.66 |
| 6 month eGFR mean (n) | 69.36(48) | 74.19(51) | 0.324 |
| AEs | 175(55.9) | 138(44.1) | 0.035 |
| Serious AEs | 85(62) | 52(38) | 0.05 |
| Drug Discontinued | 10(76.9) | 3(23.1) | 0.23 |
To cite this abstract in AMA style:
Helmick RA, Naik S, Eymard C, Eason J, Vanatta J. An Interim Report on a Prospective Randomized Trial of Extended-Release Tacrolimus in Liver Transplantation with Anti-Thymocyte Induction in a Steroid Free Protocol [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/an-interim-report-on-a-prospective-randomized-trial-of-extended-release-tacrolimus-in-liver-transplantation-with-anti-thymocyte-induction-in-a-steroid-free-protocol/. Accessed May 11, 2025.« Back to 2022 American Transplant Congress