“评价九一丹外用安全性和规范性的自身对照病例研究”的研究方案

Study protocol for a self-controlled case study to evaluate the safety and standardization for external application of Chinese medicine Jiuyi Powder

背景:升丹是中医外科外治具有提脓祛腐的主要药物,但是由于升丹含汞,有一定的毒性,虽有抗生素所不能替代的杀菌祛腐作用,在临床上使用受限,而且目前缺乏临床使用剂量和使用方法等的标准,缺少有关操作规范和毒副作用监测的相关研究。作者选择目前适用范围最广、使用频率最高的升丹类药物九一丹进行安全性研究,并期望形成临床安全使用的规范化方案。方法与设计:采用自身前后对照的病例研究,研究分两阶段。第一阶段选择粉刺性乳痈患者10例,以固定剂量(160 mg/d)连续外用九一丹,多时点检测患者外用九一丹后的血汞和尿汞水平,了解创面吸收九一丹后的药代动力学参数。第二阶段选择头面部术后创面、粉刺性乳痈、肛瘘和臁疮患者各30例。按照1.5 mg/cm^2的剂量外用九一丹于创面,治疗时间为14 d。根据第一阶段研究结果选择恰当的毒性指标和检测时间进行检测,以评价不同部位的外科疾病外用九一丹提脓祛腐的安全性。讨论:本研究通过两阶段的病例研究了解一定剂量范围内临床外用九一丹提脓祛腐的药代动力学参数及不同部位的外科疾病外用九一丹提脓祛腐的血汞、尿汞及相关安全性指标的变化情况,对临床外用九一丹的安全性进行评价,评估九一丹能否作为炎症性难愈性创面提脓祛腐阶段的常规用药。

Background： As the main medicinal powder for drawing out pus and removing necrotic tissue in external therapies of traditional Chinese surgery, Sheng Powder has made great contributions to the treatment of inflammatory wounds and has the unique bactericidal and decay-discharging function that can not be replaced by antibiotics. However, Sheng Powder has toxicity because it contains mercury. So far, there is no clinical research on the standards of dose and usage of Sheng Powder and there is a lack of objective and quantitative criteria for operating standards and monitoring of toxicity and side effects. Therefore, the authors choose Jiuyi Powder, one of the most commonly used Sheng Powder, to evaluate the safety of its external use, and form a standardization program for clinical implementation. Methods and design： This study is a nonrandomized, nonblinded, self-controlled case study. There will be two key stages in the study. In stage one, 10 patients with plasma cell mastitis will be enrolled. The patients will receive continuous external application of Jiuyi Powder with a fixed dose （160 mg/d）. Blood mercury and urine mercury levels will be dynamically tested at different time intervals, and the observation of pharmacokinetic parameters will be conducted after Jiuyi Powder has been absorbed by the surface of the wound. In stage two, 30 patients with each of the four conditions including postoperative wounds of head or facial surgeries, plasma cell mastitis, anal fistula and chronic absorption ulcer of the shank will be enrolled, respectively. According to the dose of 1.5 mg/cm2, Jiuyi Powder will be externally applied to the wound surface for 14 d. On the basis of the first-phase study, the test time will be chosen and the toxicity outcome will be detected to evaluate the safety of external application of Jiuyi Powder and to establish recommendations for standardized clinical use. Discussion： The purpose of this study is to evaluate the safety of the external application of Jiuyi Powder through a two-stage study. The pharmacokinetic parameters of external application of Jiuyi Powder at the clinical dose range, the changes in blood and urinary mercury levels and related safety indexes will be observed on different wounds located in different positions externally. The evaluation of whether Jiuyi Powder could be a routine medication for drawing out pus and removing necrotic tissue in inflammatory and refractory wounds will be stated.