Iron Chelator in Contrast-Induced Acute Renal Failure

描述(由申请人提供)： 根据NIH工作人员的建议和评审员的批评，这份修订后的申请将作为R33申请重新提交。修订后的申请现在是一项多中心试验，涉及经验丰富的调查人员詹姆斯·A·图姆林医学博士(Emory)、帕特里克·T·默里医学博士(芝加哥大学)和由迈克尔·库特纳博士领导的著名生物统计中心。有大量证据表明氧化剂和铁(可参与自由基反应)在实验性急性肾功能衰竭模型中的重要性。然而，铁络合剂在预防人类ARF中的作用以前还没有得到检验。我们假设去铁酮，一种口服铁络合剂，可以在接受放射造影剂研究的患者中预防ARF。 我们建议研究CRI患者心脏手术后放射造影剂引起的肾病，因为这是一种明确的临床情况，很容易识别和监测。此外，造影剂通常用于各种诊断和治疗程序。我们建议开展的研究选择心导管检查，而不是需要使用造影剂的非冠脉手术，原因是：1)接受心导管检查的患者ARF的发生率要高得多，因此需要的患者更少；2)对于大多数患者来说，心导管检查(如果有适应症)是不能推迟的，即使是那些发生ARF的高风险患者，而需要进行非心脏造影剂检查的类似受试者通常有其他相对安全的选择(如MRI)。 拟议研究的主要目标是： 1.比较CRI患者接受心导管插管，每天两次口服长效去铁酮1800 mg与安慰剂治疗ARF的发生率。 2.为确定去铁酮缓释片1800 mg口服的安全性，每天两次，在心导管术前一天及当天。

DESCRIPTION (provided by applicant): This revised application is being resubmitted as an R33 application based on the recommendation of the NIH staff and the reviewers' critique. The revised application is now a multicenter trial involving experienced investigators James A. Tumlin, MD (Emory), Patrick T. Murray, MD (University of Chicago), and a well-established biostatistic center headed by Michael Kutner, PhD. There is a large body of evidence indicating the importance of oxidants and iron (which can participate in free radical reactions) in models of experimental acute renal failure. However, the effect of iron chelators in preventing ARF in humans previously has not been examined. We hypothesize that deferiprone, an oral iron chelator, can prevent ARF in patients undergoing a radiocontrast study. We propose to study radiocontrast medium-induced nephropathy after cardiac procedures in patients with CRI because this is a well-defined clinical situation that is easy to recognize and monitor. Furthermore, contrast medium is commonly used for various diagnostic and therapeutic procedures. Cardiac catheterization is selected for our proposed study as opposed to non-coronary procedures requiring contrast use because: 1) the incidence of ARF is much higher in patients undergoing cardiac catheterization and therefore fewer patients will be required 2) cardiac catheterization (when indicated) cannot be deferred in most patients, even in those who are at high risk for developing ARF, while similar subjects requiring a non-cardiac contrast study usually have other relatively safe options available (e.g., MRI). The Primary objectives of the proposed study are: 1.To compare the incidence of ARF in patients with CRI undergoing cardiac catheterization and receiving long-acting deferiprone 1800 mg orally twice a day versus placebo, one day prior to and on the day of the procedure. 2. To ascertain the safety of deferiprone 1800 mg sustained-release administered orally, twice a day, one day prior to, and on the day of cardiac catheterization.