Liver cystic echinococcosis: pre-clinical assessment of a novel, single step percutaneous treatment procedure (intracystic albendazole sulfoxide injection)

肝囊型包虫病：新型单步经皮治疗程序（囊内阿苯达唑亚砜注射液）的临床前评估

• 批准号: 9072551
• 负责人: Saul J Santivanez
• 金额: $ 13.5万
• 依托单位: UNIVERSIDAD PERUANA CAYETANO HEREDIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-07 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9072551
• 关键词: Affect; Africa; Albendazole; Animals; Antiparasitic Agents; Area; Argentina; Australia; Biliary; Biliary Fistula; Biochemical; Biological Assay; Central Asia; China; Clinical; Clinical Trials; Clinical assessments; Collection; Communicable Diseases; Country; Cyst; Data; Development; Dipylidium caninum; Disease; Dose; Echinococcosis; Echinococcus granulosus; Evaluation; Evolution; Future; Hand; Hepatic; Hepatic Cyst; Human; Injectable; Injection of therapeutic agent; Liver; Liver diseases; Livestock; Lung diseases; Medical; Mediterranean Region; Methods; Modality; Modeling; Operative Surgical Procedures; Oral; Parasitic Diseases; Patients; Performance; Peru; Pharmacology and Toxicology; Placebo Control; Population; Preparation; Principal Investigator; Procedures; Public Health; Puncture procedure; Randomized Controlled Trials; Research; Research Personnel; Resources; Russia; Safety; Sheep; Sodium Chloride; Solvents; South America; Staging; Sulfoxide; Technology Transfer; Testing; Time; Toxic effect; Training; Ultrasonography; Water; base; blind; cost; effective therapy; improved; interest; novel; novel therapeutic intervention; pre-clinical; prevent; public health relevance; randomized placebo controlled trial; safety study; success; systemic toxicity; unnecessary treatment

 DESCRIPTION (provided by applicant): Cystic echinococcosis (CE), a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus, is endemic to areas where livestock are raised including Eurasia, UK, Australia, South America and North and East Africa, and considered a serious and costly public health problem in endemic regions. Liver CE is the most common clinical presentation, representing around 70% of human CE cases. Treatment procedures for liver CE have evolved over the past four decades. Currently, four treatment modalities are used: (1) medical treatment with albendazole (ABZ), (2) PAIR (Puncture, Aspiration, Injection of protoscolicidal agent; Reaspiration), (3) surgery to remove the cyst and (4) watch and wait for inactive, clinically silent cysts. In most endemic countries, surgery is the main treatment approach for liver cysts. PAIR has gained ground in the treatment of liver CE and can be performed in centers with limited resources as much as ultrasound guiding is available. PAIR however has some technical drawbacks that include the need to rule out the presence of a cysto-biliary fistula, and is not completely efficacious. A simpler, safer an more effective treatment approach would be of great benefit for patients in endemic regions. The current proposal will evaluate a new treatment approach that consists on a single step injection of albendazole sulfoxide (ABZ-SF), the active metabolite of ABZ, into the cyst. This procedure is less resource and time demanding than PAIR, should not be hampered by the presence of cysto-biliary fistula, and should also be safer than oral ABZ therapy since it avoids the systemic toxicity associated with a prolonged therapy with oral ABZ. The first project is a pilot placebo controlled experimental / interventional animal safety study comparing two different doses of ABZ-SF to determine the higher safe doses as well as to provide preliminary information about efficacy of the antiparasitic drug injection. The second study is a blind, placebo controlled randomized trial testing the highest safe dose of ABZ-SF identified in study 1. Finally, in a third study, which is also a blind, controlled randomized trial, we will determine the minimal needed concentration of intracystic ABZ-SF to achieve treatment success. This proposal can eventually provide a new therapeutic approach for human liver CE, and should result in an R34 application for a future human trial.

 描述（由申请方提供）：囊状棘球蚴病（CE）是一种由犬绦虫细粒棘球绦虫幼虫期引起的人畜共患疾病，在包括欧亚大陆、英国、澳大利亚、南美洲以及北非和东非在内的牲畜饲养地区流行，在流行地区被认为是一种严重且代价高昂的公共卫生问题。肝脏CE是最常见的临床表现，约占人类CE病例的70%。肝脏CE的治疗程序在过去四十年中不断发展。目前，使用了四种治疗方式：（1）用阿苯达唑（ABZ）进行医学治疗，（2）PAIR（穿刺、抽吸、注射杀原生真菌剂;再抽吸），（3）手术移除肿瘤，（4）使用抗真菌药物治疗。 囊肿和（4）观察和等待不活跃的，临床上沉默的囊肿。在大多数流行国家，手术是肝囊肿的主要治疗方法。PAIR已在肝脏CE治疗中取得进展，可以在资源有限的中心进行，只要有超声引导。然而，PAIR有一些技术缺陷，包括需要排除膀胱胆瘘的存在，并且不是完全有效的。一种更简单、更安全、更有效的治疗方法将对流行地区的患者大有裨益。目前的建议将评估一种新的治疗方法，包括一个单一的步骤注射阿苯达唑亚砜（ABZ-SF），ABZ的活性代谢产物，进入囊肿。这种方法比PAIR需要更少的资源和时间，不应该受到膀胱胆瘘的阻碍，并且也应该比口服ABZ治疗更安全，因为它避免了与口服ABZ长期治疗相关的全身毒性。第一个项目是一项安慰剂对照实验/干预性动物安全性试验，比较两种不同剂量的ABZ-SF，以确定更高的安全剂量，并提供有关抗寄生虫药物注射有效性的初步信息。第二项研究是一项盲法、安慰剂对照随机试验，测试研究1中确定的ABZ-SF的最高安全剂量。最后，在第三项研究中，这也是一项盲法对照随机试验，我们将确定 囊内ABZ-SF达到治疗成功所需的最低浓度。这一提议最终可以为人类肝脏CE提供一种新的治疗方法，并将导致R34应用于未来的人体试验。