De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial

Clin Transplant. 2021 Dec;35(12):e14487. doi: 10.1111/ctr.14487. Epub 2021 Oct 1.

Abstract

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Keywords: calcineurin inhibitor; clinical trial; heart (allograft) function/dysfunction; immunosuppressant; patient survival; tacrolimus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Tablets
  • Tacrolimus / therapeutic use

Substances

  • Delayed-Action Preparations
  • Immunosuppressive Agents
  • Tablets
  • Tacrolimus