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降低儿童心脏手术时接受同种异体瓣膜移植的同种免疫反应。19名患者参加了这项研究，但有6名患者因各种原因退出了研究。在随机接受硫唑嘌呤治疗的组中，有4例患者变得无法评估。1例患者在手术24小时内死于低心输出量；一名患者因静脉穿刺取血困难，应患者要求退出；两名患者被负责的外科医生撤院，一名患者因革兰氏阳性菌血症对静脉注射抗生素有反应，另一名患者因粪便呈艰难梭菌阳性。在对照组中，一名患者在手术后4周死于低心排血量，一名患者因静脉穿刺取血困难而退出手术。在目前登记或已完成研究的13名患者中，6名患者接受了硫唑嘌呤治疗，7名患者为对照组。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总反应性抗体水平没有显著差异。由于轻度转氨酶升高和轻度中性粒细胞减少症，用硫唑嘌呤治疗的患者需要在3个月后减少剂量。减少剂量后，所有实验室指标均恢复正常。本研究将确定更多的患者，直到有足够数量的患者具有统计能力，使研究人员能够确定治疗是否会降低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patient withdrew at the patient's request because of difficulty in obtaining blood by venipuncture; two patients were withdrawn by the responsible surgeon, one because of gram-positive bacteremia that responded to intravenous antibiotics, and one because of Clostridium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.