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Clinical Trial
. 2020 Jan 7;15(1):109-116.
doi: 10.2215/CJN.04840419. Epub 2019 Dec 16.

Three-Year Outcomes of a Randomized, 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

Edmund Huang  1 , Ashley Vo  1 , Jua Choi  1 , Noriko Ammerman  1 , Kathlyn Lim  1 , Supreet Sethi  1 , Irene Kim  2 , Sanjeev Kumar  1 , Reiad Najjar  1 , Alice Peng  1 , Stanley C Jordan  1
Affiliations
Clinical Trial

Three-Year Outcomes of a Randomized, 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

Edmund Huang et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: Delayed graft function is related to ischemia-reperfusion injury and may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated with a shorter duration of delayed graft function and higher eGFR at 1 year. Here, we report longer-term outcomes from this trial.

Design, setting, participants, & measurements: This is a post hoc analysis of a phase 1/2, randomized, controlled trial enrolling 70 recipients of deceased donor kidney transplants at risk for delayed graft function (NCT02134314). Subjects were randomized to receive C1 esterase inhibitor 50 U/kg (n=35) or placebo (n=35) intraoperatively and at 24 hours. The cumulative incidence functions method was used to compare graft failure and death over 3.5 years. eGFR slopes were compared using a linear mixed effects model.

Results: Three deaths occurred among C1 esterase inhibitor-treated patients compared with none receiving placebo. Seven graft failures developed in the placebo group compared with one among C1 esterase inhibitor-treated recipients; the cumulative incidence of graft failure was lower over 3.5 years among C1 esterase inhibitor-treated recipients compared with placebo (P=0.03). Although no difference in eGFR slopes was observed between groups (P for group-time interaction =0.12), eGFR declined in placebo-treated recipients (-4 ml/min per 1.73 m2 per year; 95% confidence interval, -8 to -0.1) but was stable in C1 esterase inhibitor-treated patients (eGFR slope: 0.5 ml/min per 1.73 m2 per year; 95% confidence interval, -4 to 5). At 3.5 years, eGFR was 56 ml/min per 1.73 m2 (95% confidence interval, 42 to 70) in the C1 esterase inhibitor group versus 35 ml/min per 1.73 m2 (95% confidence interval, 21 to 48) in the placebo group, with an estimated mean eGFR difference of 21 ml/min per 1.73 m2 (95% confidence interval, 2 to 41 ml/min per 1.73 m2).

Conclusions: Treatment of patients at risk for ischemia-reperfusion injury and delayed graft function with C1 esterase inhibitor was associated with a lower incidence of graft failure.

Keywords: complement C1 inhibitor protein; complement c1s; death; delayed graft function; double-blind method; epidermal growth factor receptor; glomerular filtration rate; human EGFR protein; humans; incidence; ischemia-reperfusion; kidney transplantation; reperfusion injury; tissue donors.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Study flowchart. There were a total of 70 patients randomized, 35 each to the C1 esterase inhibitor and placebo groups. No patients were excluded from the analysis.
Figure 2.
Figure 2.
Cumulative incidence of graft failure and death among placebo-treated and C1 esterase inhibitor–treated patients. There was a higher incidence of graft failure and no difference in the incidence of death over 3.5 years in the placebo group compared to the C1 esterase inhibitor group. Event-free survival was not different between the groups.
Figure 3.
Figure 3.
Kaplan–Meier curve for rejection-free survival comparing C1 esterase inhibitor–treated and placebo-treated patients. There was no difference in rejection-free survival over 3.5 years between the C1 esterase inhibitor and placebo groups.
Figure 4.
Figure 4.
Comparison of eGFR over time among C1 esterase inhibitor–treated and placebo-treated patients. The eGFR slope was stable in the C1 esterase inhibitor group but declined in the placebo group over the study period. At 3.5 years, eGFR was higher among C1 esterase inhibitor-treated recipients compared to placebo-treated patients.
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References

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