PROSPECTIVE STUDY TO DETERMINE THE EFFICACY AND SAFETY OF AZATHIOPRINE

本研究的目的是确定硫唑嘌呤是否能降低小儿心脏手术时接受瓣膜同种异体移植的儿童的同种免疫反应。 19例患者入组本研究，但6例因各种原因退出。 在随机接受硫唑嘌呤的组中，有4名患者无法评估。 1例患者在手术后24小时内死于低心输出量; 1例患者因静脉穿刺采血困难应患者要求退出; 2例患者由责任外科医生退出，1例患者因革兰氏阳性菌血症对静脉注射抗生素有反应，1例患者因艰难梭菌阳性粪便。 在对照组中，1例患者在术后4周死于低心排血量，1例患者因静脉穿刺采血困难而退出研究。在目前入选或已完成研究的13例患者中，6例接受硫唑嘌呤治疗，7例为对照组。 迄今为止，在手术后1个月或3个月，治疗组和对照组之间的群体反应性抗体水平无显著差异。 接受硫唑嘌呤治疗的患者在3个月后需要减量，因为转氨酶轻度升高和轻度中性粒细胞减少。 剂量降低后，所有实验室检查值均恢复正常。本研究将确定额外的患者，直到有足够的数量可用于具有统计学把握度，使研究者能够确定治疗是否降低PRA滴度。

The objective of this study is to determine if azathioprine reduces the alloimmune response in children who receive valved allografts at the time of pediatric heart surgery. Nineteen patients have been enrolled in this study, but six withdrew for various reasons. In the group randomized to receive azathioprine, four patients became inevaluable. One patient died within 24 hours of surgery from low cardiac output; one patient withdrew at the patient's request because of difficulty in obtaining blood by venipuncture; two patients were withdrawn by the responsible surgeon, one because of gram-positive bacteremia that responded to intravenous antibiotics, and one because of Clostridium difficile-positive stools. In the control groups, one patient died four weeks after surgery from low cardiac output, and one patient withdrew because of difficulty in obtaining blood by venipuncture. Of the thirteen patients currently enrolled, or who have completed the study, six were treated with azathioprine and seven were in the control group. To date, there is no significant difference in the level of panel-reactive antibodies between the treated group and the control group at the one-month point or at three months after surgery. Patients treated with azathioprine required dose reductions after three months because of mild liver elevations in transaminases and mild neutropenia. All laboratory values returned to normal after dose reduction. Additional patients will be ascertained for this study until a sufficient number are available to have statistical power enabling the investigators to determine if the therapy decreases the titer of PRA or not.