Impact of Extended- versus Immediate-Release Tacrolimus on One-Year Development of De Novo DSA and Chronic Immune Activation in Kidney Transplantation (ASTOUND Study)
1University of Colorado Hospital, Aurora, CO, 2University of Wisconsin, Madison, WI, 3Henry Ford Hospital, Detroit, MS, 4Massachusetts General Hospital, Boston, MA, 5Northwestern University, Chicago, IL, 6Astellas Pharma Global Development, Northbrook, IL
Meeting: 2020 American Transplant Congress
Abstract number: LB-5
Keywords: Immunosuppression, Kidney transplantation, Multicenter studies
Session Information
Session Name: Late Breaking Oral Abstract
Session Type: Oral Abstract Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:45pm
Presentation Time: 4:03pm-4:15pm
Location: Virtual
*Purpose: To compare, using an adaptive study design, the 1-year incidence of a novel two-part composite endpoint consisting of de novo donor-specific antibody (dnDSA) formation and/or immune activation (IA) in kidney transplant (Ktx) recipients maintained on extended- (ERT) vs immediate-release tacrolimus (IRT).
*Methods: In this exploratory, prospective, multicenter, randomized, open-label trial (NCT02723591), 599 adult Ktx recipients were randomized 1:1 to receive once daily ERT (Astagraf XL®, Astellas Pharma US, Inc.) or twice daily IRT maintenance immunosuppression with corticosteroids and mycophenolate mofetil (target tacrolimus trough concentration ≥6 ng/mL). Positivity for dnDSA was defined as MFI >1000. IA was defined as a positive peripheral blood molecular signature as measured by the Trugraf™ v2.0 molecular assay (Transplant Genomics, Inc., USA). The difference in the proportion of patients meeting the primary composite endpoint was assessed by testing the null hypothesis of no treatment effect (H0: odds ratio [OR]=1; multivariable logistic regression analysis).
*Results: Safety was analyzed in 575 and efficacy in 554 patients (confirmed DSA negative at time of tx; ERT, n=275; IRT, n=279). By Day 365, incidence of the novel primary composite endpoint (dnDSA and/or IA) was 35.6% in the ERT group vs 34.4% in the IRT group (Table). Adjusted OR for ERT vs IRT was 1.12 (95% CI: 0.76, 1.64; p=0.58). Incidence of the traditional four-part composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up was 9.1% vs 10.4%, respectively. Mean relative improvements in eGFR from Day 30 to Day 365 were 19.7% for ERT and 20.8% for IRT (respective mean increase, 6.04 vs 6.39 mL/min/1.73 m²). Mean eGFR at Day 365 was 58.25 vs 60.86 mL/min/1.73 m². BK virus was reported in 15.6% and 12.9% of patients, respectively. No unexpected safety findings were reported.
*Conclusions: This is the first large-scale RCT in the field of solid organ tx to use potential biomarkers as the primary outcome measure. At 1 year post tx, incidence rates of dnDSA formation and BPAR were similar with ERT and IRT. dnDSA rates were lower than historically reported. Both tacrolimus formulations yielded 1-year death-censored graft survival >98% under contemporary US practice conditions.
To cite this abstract in AMA style:
Wiseman A, Kaufman D, Patel A, Wojciechowski D, Tambur A, Kim J, Schwartz J. Impact of Extended- versus Immediate-Release Tacrolimus on One-Year Development of De Novo DSA and Chronic Immune Activation in Kidney Transplantation (ASTOUND Study) [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-extended-versus-immediate-release-tacrolimus-on-one-year-development-of-de-novo-dsa-and-chronic-immune-activation-in-kidney-transplantation-astound-study/. Accessed May 11, 2025.« Back to 2020 American Transplant Congress