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

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.

Bioimpedance Spectroscopy in Heart Transplantation: Posttransplant Changes in Body Composition and Effects in Outcomes

“…Local protocols did not include medications interacting with agents in the immunosuppression regimen. 16…”

“…Local protocols did not include medications interacting with agents in the immunosuppression regimen. 16 Clinical Outcomes BIS-derived elements, including fat mass, fat-free mass, and phase angle, were compared with preoperative variables for correlation of malnutrition assessment and predictability of adverse clinical events, including mortality and rejection at 1 and 4 y, initial hospital length of stay, all-cause hospital readmission, and hospital readmission because of infection. Rejection was defined as acute cellular rejection with grade ≥2R according to the International Society for Heart Lung Transplantation-2004 Scale 17 or antibody-mediated rejection (AMR) with grades AMR ≥ pathologic AMR1, per International Society for Heart Lung Transplantation-2013 AMR Scale.…”

Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis

“…Pharmacokinetics: TAC is formulated in oral, intravenous, and topical dosage forms (Table 1). The oral dosage form is designed in different release patterns: immediate, slow, and extended release [47]. It combines with one or more therapies such as monoclonal antibody-basiliximab, or drugs, such as sirolimus, azathioprine, mycophenolate mofetil, and steroids [48][49][50].…”

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation

“…LCPT was recently studied in heart transplant in a phase 2, single-center, open-label, non-inferior matched control study of 25 recipients who were matched 1:2 with a historical IR-TAC control. 83 Patients were maintained on MPA and corticosteroids that tapered off by 6 months. LCPT was noninferior to IR-TAC for the composite endpoint of death, acute cellular rejection and/or new allograft dysfunction within 1 year (20% vs. 40%, CI -40% to −0.5%).…”