Combined Albendazole Plus Praziquantel in Subarachnoid NCC, DCC Application

阿苯达唑联合吡喹酮在蛛网膜下腔 NCC、DCC 中的应用

• 批准号: 9323836
• 负责人: Andres G Lescano
• 金额: $ 8.03万
• 依托单位: UNIVERSIDAD PERUANA CAYETANO HEREDIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323836
• 关键词: Address; Affect; Aftercare; Albendazole; Antigens; Antiparasitic Agents; Brain; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Communication Programs; Cysticercosis; Data; Data Collection; Data Coordinating Center; Developing Countries; Disease; Double-Blind Method; Ecuador; Enrollment; Epilepsy; Fissural; Frequencies; Funding; Goals; Growth; Human; Human Resources; Hydrocephalus; Infection; Inflammatory; Institutes; Institution; Intracranial Hypertension; Knowledge; Larva; Lead; Lesion; Magnetic Resonance Imaging; Maintenance; Measures; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neurocysticercosis; Parasites; Parasitic infection; Patients; Peru; Praziquantel; Procedures; Process; Quality Control; Randomized; Regimen; Research; Research Design; Resolution; Resources; Role; Safety; Scanning; Scientist; Secure; Seizures; Serious Adverse Event; Serum; Solid; Standardization; Statistical Data Interpretation; Steroids; Sylvius fissure; Symptoms; System; Taenia solium; Testing; Therapeutic; Treatment Protocols; analytical method; brain tissue; computerized; control trial; data integrity; data management; design; experience; improved; instrument; mortality; nervous system disorder; neuroimaging; patient safety; public health relevance; randomized placebo controlled trial; randomized trial; response; secondary outcome; standard of care

 DESCRIPTION (provided by applicant): Neurocysticercosis (NCC) is the infection of the human nervous system by the larvae of the pork tapeworm Taenia solium. Subarachnoid neurocysticercosis (SANCC) accounts for 20-35% of all NCC cases. It is an aggressive, progressive and frequently lethal presentation of NCC, endemic in most non-Muslim developing countries. Unlike intraparenchymal disease (where the predominant manifestation is seizures and epilepsy, and parasites are located in the brain tissue), in subarachnoid disease the presence of the parasitic masses in the surroundings of the brain, their growth, and the concomitant inflammatory process lead to mass effect, intracranial hypertension and/or hydrocephalus, resulting in heavy morbidity and significant mortality which can be more than 20%. The response to antiparasitic treatment in SANCC is usually slow and partial, but if complete parasite resolution is obtained patients may be cured without further symptoms. This application naturally expands the scope of and applies the knowledge obtained from a recent NINDS-funded trial on combined albendazole (ABZ) plus praziquantel (PZQ) treatment of intraparenchymal NCC [R01 NS054805]. The current treatment regimens for SANCC have quite limited efficacy and the disease is still associated with significant mortality in many places of te world. Combining ABZ and PZQ, along with appropriate steroid coverage and other safety measures, is the logical next step to improve the management of subarachnoid NCC and has not been examined before in a controlled trial. In this double-blind, randomized, placebo-controlled study, 164 patients with subarachnoid cysticercosis of the basal cisterns or the Sylvain fissure, will be assigned to either the standard of care anti- parasitic regime (30-day ABZ at 15 mg/k/d) or a combined regime adding PZQ at 50 mg/k/d for the initial 15 days of anti-parasitic treatment. The primary study endpoint is the proportion of patients with disappearance of their parasitic lesions in neuroimaging at six months after therapy onset. Secondary outcomes include the decrease in volume of parasitic masses measured by MRI at 3 and 6 months after treatment onset, clinical improvement evaluated as the proportion of patients asymptomatic and without need for further antiparasitic treatment 6 months post-treatment, the frequency of serious adverse events (SAE) of the combined regime compared to the standard of care, the decrease in the serum levels of circulating parasitic antigen at 3 and 6 months after treatment onset, and the proportion of patients whose lesions resolve and do not relapse by 12 months after treatment onset. The trial will initially involve four centers: two in Peru, one in Brasil and one in Ecuador with the potential to expand to more centers if required. By comparing two active regimes, the proposed parallel group design permits open assessment of control neuroimaging scans for patient safety without affecting treatment blinding, and will provide the first data to support either therapeutic change or maintenance of the standard of care. If this tril succeeds, it will provide a new, more appropriate standard of care, available worldwide.

 描述（由申请人提供）：神经囊尾蚴病 (NCC) 是由猪带绦虫幼虫引起的人类神经系统感染，占所有 NCC 病例的 20-35%。 NCC 呈进行性且经常致命的表现，在大多数非穆斯林发展中国家流行，与实质内疾病不同（其中主要表现是癫痫发作和癫痫，寄生虫位于脑组织中），在蛛网膜下腔疾病中，大脑周围寄生虫肿块的存在、它们的生长以及伴随的炎症过程导致占位效应、颅内高压和/或脑积水，导致严重的发病率和显着的死亡率，可超过 20%。 SANCC 抗寄生虫治疗的反应通常缓慢且部分，但如果寄生虫完全消退。该应用自然扩大了 NINDS 资助的最近一项阿苯达唑 (ABZ) 加吡喹酮 (PZQ) 联合治疗实质内 NCC 试验的范围并应用了该试验的知识 [R01 NS054805]。 SANCC 的治疗方案疗效相当有限，并且结合 ABZ 和 PZQ，该疾病在世界许多地方仍然与显着的死亡率相关。结合适当的类固醇覆盖和其他安全措施，是改善蛛网膜下腔 NCC 治疗的合理下一步，并且之前尚未在一项对照试验中进行过检查。在这项双盲、随机、安慰剂对照研究中，有 164 名蛛网膜下腔患者参与。基底池或西尔万裂囊虫病，将被分配到标准护理抗寄生虫方案（30 天 ABZ，15 mg/k/d）或在抗寄生虫治疗的最初 15 天中添加 50 mg/k/d PZQ 的联合方案主要研究终点是治疗开始后 6 个月时神经影像学中寄生虫病灶消失的患者比例。治疗开始后 3 个月和 6 个月时通过 MRI 测量的寄生虫肿块体积的减少，以治疗后 6 个月无症状且无需进一步抗寄生虫治疗的患者比例来评估临床改善，与标准治疗相比，联合治疗方案严重不良事件 (SAE) 的频率、治疗开始后 3 个月和 6 个月时循环寄生虫抗原血清水平的下降，以及病变消退且不复发的患者比例治疗开始后 12 个月内，该试验最初将涉及四个中心：两个在秘鲁，一个在巴西，一个在厄瓜多尔，如果需要，有可能扩展到更多中心。控制神经影像学评估在不影响治疗盲法的情况下对患者安全进行扫描，并将提供第一批数据来支持治疗改变或护理标准的维持。如果这项试验成功，它将在全球范围内提供一种新的、更合适的护理标准。