Date: Sunday, June 3, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
- A Phase I/II, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients
- Eculizumab in Prevention of Acute Antibody-Mediated Rejection in Sensitized Deceased-Donor Kidney Transplant Recipients: 1-Year Outcomes
DGF portends poor short- and long-term renal function, increases cost, and may reduce graft survival. We studied the safety/efficacy of eculizumab (ECU), a C5 convertase inhibitor, in 2 related, investigator sponsored trials with funding provided by Alexion. 27 crossmatch- and DSA-neg recipients (8 from Sinai in 1st, 19 from 8 sites in 2nd) were enrolled (of 68 planned). Enrollment criteria were similar in the 2 studies including: ECD kidneys with brain death (kidney donors ≥60 y or age 50-59 and 2 of the following 3: hypertension, terminal serum cre >1.5 mg/dl, or death from CVA), or SCD kidneys with actual cold ischemic time (CIT) of 18-40 h. Recipients received meningococcal vaccine prior to transplantation. Patients received ATG followed by standard dose TAC, MMF and steroids and were randomized to receive 1200 mg ECU (n=16) or saline (n=11), with infusion initiated prior to organ reperfusion in the OR. In the 2nd study, a 2nd 900 mg dose of ECU was administered 12-24 h after the initial dose. The primary endpoint was the incidence of DGF defined as need for dialysis within the first week (excluding hyperkalemia or vol. overload in 1st 8 patients). Combined data analysis show the median age of 58 y, 17/27 male, 12/27 African American, and 15/27 with type II DM. There were no epidemiological or immunological differences btw groups. CIT was 22.6 (control) vs 23.8 h (ECU, p=ns). ECU was well tolerated with similar severe adverse event (SAE) rates; 2 ECU patients and no controls experienced infectious SAE (wound, UTI). There were no meningo/pneumococcal infections. Incidence of DGF was 5/11 (45%) controls vs 7/16 (44%) ECU (p=ns). Urine output on d1 and 7 did not differ, nor did the rate of reduction of serum Cre d 0-7. The study was halted prior to completing enrollment because results of a randomized trial of 286 patients performed independently by Alexion with similar design showed no efficacy for ECU in preventing DGF. Our findings do not support intraoperative, pre-reperfusion ECU to prevent DGF in deceased donor kidney transplantation.
CITATION INFORMATION: Heeger P., Akalin E., Baweja M., Bloom R., Florman S., Haydel B., Hricik D., Kulkarni S., Mehrotra A., Patel A., Poggio E., Ratner L., Schröppel S., Shapiro R. Lack of Efficacy of Eculizumab for Prevention of Delayed Graft Function (DGF) in Deceased Donor Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Heeger P, Akalin E, Baweja M, Bloom R, Florman S, Haydel B, Hricik D, Kulkarni S, Mehrotra A, Patel A, Poggio E, Ratner L, Schröppel S, Shapiro R. Lack of Efficacy of Eculizumab for Prevention of Delayed Graft Function (DGF) in Deceased Donor Kidney Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/lack-of-efficacy-of-eculizumab-for-prevention-of-delayed-graft-function-dgf-in-deceased-donor-kidney-transplant-recipients/. Accessed March 26, 2019.
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