Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial.
Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial.
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DOI：
10.1111/j.1600-6143.2012.04212.x
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
H2304 Study Group
中科院分区：
文献类型：
--
作者：
De Simone P;Nevens F;De Carlis L;Metselaar HJ;Beckebaum S;Saliba F;Jonas S;Sudan D;Fung J;Fischer L;Duvoux C;Chavin KD;Koneru B;Huang MA;Chapman WC;Foltys D;Witte S;Jiang H;Hexham JM;Junge G;H2304 Study Group
在一项前瞻性、多中心、开放标签研究中，初治肝移植患者在第30±5天被随机分配至（i）依维莫司开始给药伴他克莫司消除（TAC消除）（ii）依维莫司开始给药伴他克莫司减少暴露（EVR+减少TAC）或（iii）他克莫司标准暴露（TAC对照）。由于经治疗的活检证实的急性排斥反应（tBPAR）发生率较高，提前终止了随机分配至TAC消除组。EVR+减少TAC的主要疗效终点（tBPAR、移植后12个月移植物丢失或死亡）不劣于TAC对照：6.7% vs 9.7%（−3.0%; 95% CI −8.7，2.6%;非劣效性p<0.001 [12%界值]）。2.9%的EVR+ TAC降低患者发生tBPAR，而TAC对照组为7.0%（p = 0.035）。EVR+减少TAC组从随机化至第12个月的校正估计GFR变化上级TAC对照组（差异为8.50 mL/min/1.73 m2，97.5% CI 3.74，13.27 mL/min/1.73 m2，p<0.001，优效性）。EVR+ TAC降低组和TAC对照组中因不良事件停药的发生率分别为25.7%和14.1%（相对风险1.82，95% CI 1.25，2.66）。EVR+减少TAC组与TAC对照组之间严重感染的相对风险为1.76（95% CI 1.03，3.00）。与肝移植后12个月的标准他克莫司暴露方案相比，依维莫司有助于早期他克莫司最小化，具有相当的疗效和更好的上级肾功能。
In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.
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