Combined Albendazole and Praziquantel in Subarachnoid NCC, CCC, Lead application

描述（由申请人提供）：神经囊虫病（NCC）是由猪带绦虫的幼虫感染人类神经系统。蛛网膜下神经囊虫病（SANCC）占所有NCC病例的20-35%。它是一种侵袭性、进行性和经常致命的NCC表现形式，在大多数非穆斯林发展中国家流行。与实质内疾病（主要表现为癫痫发作和癫痫，寄生虫位于脑组织）不同，蛛网膜下腔疾病在脑周围存在寄生肿块，它们的生长和伴随的炎症过程导致肿块效应、颅内高压和/或脑积水，导致高发病率和高死亡率，可超过20%。在SANCC中，抗寄生虫治疗的反应通常是缓慢和部分的，但如果寄生虫得到完全消除，患者可能会痊愈，没有进一步的症状。这项申请自然扩大了范围，并应用了最近由ninds资助的阿苯达唑（ABZ）和吡喹酮（PZQ）联合治疗肺实质内NCC的试验所获得的知识[R01 NS054805]。目前的治疗方案对SANCC的疗效相当有限，并且该疾病在世界许多地方仍然与高死亡率有关。结合ABZ和PZQ，以及适当的类固醇覆盖和其他安全措施，是改善蛛网膜下腔NCC管理的合乎逻辑的下一步，之前没有在对照试验中进行过检查。在这项双盲、随机、安慰剂对照的研究中，164例基底池或Sylvain裂隙蛛网膜下腔囊虫病患者将被分配到标准抗寄生虫治疗方案（30天ABZ剂量为15mg /k/d）或在最初的15天抗寄生虫治疗中添加PZQ剂量为50mg /k/d的联合方案。主要研究终点是在治疗开始后6个月神经影像学检查中寄生虫病变消失的患者比例。次要结局包括治疗开始后3个月和6个月MRI测量的寄生虫肿块体积减少，临床改善评估为治疗后6个月无症状且无需进一步抗寄生虫治疗的患者比例，与标准护理相比，联合方案的严重不良事件（SAE）频率，治疗开始后3个月和6个月血清循环寄生虫抗原水平下降。在治疗开始12个月后病变消退且不复发的患者比例。这项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，可能会扩展到更多的中心。通过比较两种有效方案，提出的平行组设计允许在不影响治疗盲法的情况下对对照神经成像扫描进行开放评估，以确保患者的安全性，并将提供支持治疗改变或维持标准护理的第一批数据。如果试验成功，它将为全世界提供一种新的、更合适的护理标准。

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.