Results Of The Ctot19 Trial: Infliximab (IFX) Induction Does Not Impact 2-year Outcomes In Deceased Donor Kidney Transplant Recipients

P. Heeger¹, B. Armstrong², T. Alhamad³, D. Brennan⁴, J. Bromberg⁵, S. Bunnapradist⁶, S. Chandran⁷, R. Fairchild⁸, D. Foley⁹, R. Formica¹⁰, I. W. Gibson¹¹, D. Hricik¹², K. Kesler², R. B. Mannon¹³, M. Menon¹⁰, K. Newell¹⁴, P. Nickerson¹¹, J. Odim¹⁵, E. Poggio⁸, R. Sung¹⁶, R. Shapiro¹, K. Tinckam¹⁷, F. Vincenti⁷

¹Mount Sinai, New York, NY, ²Rho, Durham, NC, ³Washington U, Saint Louis, MO, ⁴Johns Hopkins, Baltimore, MD, ⁵U Maryland, Baltimore, MD, ⁶UCLA, Los Angeles, CA, ⁷UCSF, San Francisco, CA, ⁸Cleveland Clinic, Cleveland, OH, ⁹U Wisconsin, Madison, WI, ¹⁰Yale, New Haven, CT, ¹¹U Manitoba, Winnipeg, MB, Canada, ¹²U Hosp Case, Cleveland, OH, ¹³U Nebraska, Omaha, NE, ¹⁴Emory, Atlanta, GA, ¹⁵NIAID NIH, Rockville, MD, ¹⁶U Michigan, Ann Arbor, MI, ¹⁷U Hlth Network, Toronto, ON, Canada

Meeting: 2022 American Transplant Congress

Abstract number: 9002

Keywords: Graft function, Kidney transplantation, Tumor necrosis factor (TNF)

Topic: Basic & Clinical Science » Basic & Clinical Science » 74 - Clinical Trials

Session Information

Session Name: Late Breaking: Clinical Trials

Session Type: Rapid Fire Oral Abstract

Date: Saturday, June 4, 2022

Session Time: 2:00pm-3:00pm

Presentation Time: 2:10pm-2:20pm

Location: Hynes Ballroom B

*Purpose: Ischemia-reperfusion (IR) of a kidney transplant (KTx) up-regulates tumor necrosis factor alpha (TNF) production within the allograft. IR-induced TNF amplifies post-KTx allograft inflammation and may negatively impact transplant outcomes.

*Methods: We tested the effects of blocking peri-KTx TNF via a randomized, double blinded, placebo controlled, phase II, clinical trial: we enrolled 242 (of planned 300) primary deceased donor KTx recipients from 14 N American centers, and randomized 225, 1:1, to receive iv infliximab (IFX) 3mg/kg or saline control (CTRL) intraoperatively, initiated prior to kidney reperfusion. All subjects in both arms received ATG induction and maintenance immunosuppression (IS) with Tacrolimus, MMF/Myfortic and Prednisone. The primary endpoint was the difference in mean 24-mo eGFR (modified MDRD) between groups. Secondary endpoints included the proportions of subjects who developed biopsy proven acute rejection (BPAR), donor specific antibody (DSA) and delayed graft function (DGF). Safety endpoints included hospitalization rates and incidences of CMV viremia or BK viremia requiring a change in IS.

*Results: The cohort was 60% male, 38% African American with a median age of 55 years. Analysis of day 7 post-KTx plasma showed 10-fold lower TNF (p<0.001) and lower IL-1b (p=0.003), IL-6 (p=0.017) and IL-8 (p=0.002) levels in IFX vs CTRL. 24-mo eGFR was 52.45 (95% CI 48.38-56.52) in IFX and 57.35 (53.18-61.52) in CTRL (p=0.097). BPAR (≥Banff 1a) within 24-mo occurred in 5.1% in IFX vs 4.2% in CTRL (p>0.99); 1 case of ABMR was observed in the cohort (IFX). Time to ACR did not differ. DSA within 24-mo occurred in <10% of subjects, p=0.163 between groups. DGF rates were 31% IFX vs 35.7% CTRL (p=0.451). Graft loss/death was 5.3% IFX vs 7.1 CTRL (p=0.499). BK viremia requiring IS change was 28.9% IFX vs 13.4% CTRL (p=0.004) with mean time to freedom from viremia of 314 d (IFX) vs 334 d (CTRL), p=0.005.

*Conclusions: Our data do not support using IFX induction in deceased donor KTx recipients. As IFX induction significantly decreased post-KTx plasma inflammatory cytokines, the findings also underscore the complexities of targeting single inflammatory effectors as a strategy to improve KTx outcomes.

To cite this abstract in AMA style:

Heeger P, Armstrong B, Alhamad T, Brennan D, Bromberg J, Bunnapradist S, Chandran S, Fairchild R, Foley D, Formica R, Gibson IW, Hricik D, Kesler K, Mannon RB, Menon M, Newell K, Nickerson P, Odim J, Poggio E, Sung R, Shapiro R, Tinckam K, Vincenti F. Results Of The Ctot19 Trial: Infliximab (IFX) Induction Does Not Impact 2-year Outcomes In Deceased Donor Kidney Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/results-of-the-ctot19-trial-infliximab-ifx-induction-does-not-impact-2-year-outcomes-in-deceased-donor-kidney-transplant-recipients/. Accessed May 22, 2025.

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