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

描述(申请人提供)：神经囊虫病(NCC)是由猪带绦虫幼虫感染人类神经系统的疾病。蛛网膜下腔脑囊虫病(SANCC)占所有NCC病例的20-35%。它是一种侵略性、进行性和经常致命的NCC，在大多数非穆斯林发展中国家流行。与实质内疾病(主要表现为癫痫和癫痫，寄生虫位于脑组织)不同，蛛网膜下腔疾病中，脑部周围寄生性肿块的存在、生长和伴随的炎症过程会导致肿块效应、颅内高压和/或脑积水，导致严重的发病率和显著的死亡率，可达20%以上。在SANCC中，抗寄生虫治疗的反应通常是缓慢的和部分的，但如果寄生虫完全消失，患者可能会被治愈，而不会出现进一步的症状。这项申请自然扩大了NINDS资助的关于阿苯达唑(ABZ)和吡喹酮(PZQ)联合治疗实质内NCC的试验所获得的知识的范围和应用[R01 NS054805]。目前对SANCC的治疗方案疗效相当有限，在世界上许多地方，这种疾病仍然与显著的死亡率有关。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，以前从未在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，164名患有基底脑池或侧裂蛛网膜下腔囊虫病的患者将被分配到标准护理抗寄生虫疗法(30天ABZ，15 mg/k/d)或联合疗法加PZQ，50 mg/k/d，最初15天的抗寄生虫治疗。主要的研究终点是在治疗开始后6个月的神经成像中寄生性病变消失的患者的比例。次要结果包括在治疗开始后3个月和6个月时磁共振成像测量的寄生虫性肿块体积的减少，以治疗6个月后无症状和不需要进一步抗寄生虫治疗的患者的比例来评估临床改善，与治疗标准相比，联合治疗方案的严重不良事件(SAE)的频率，在治疗开始3个月和6个月时血清循环寄生虫抗原水平的下降，以及在治疗开始后12个月皮损消失且未复发的患者的比例。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，可能会扩大到更多的中心。通过比较两种有效方案，拟议的平行分组设计允许在不影响治疗失明的情况下对患者安全性的控制神经成像扫描进行开放评估，并将提供支持治疗变化或维持护理标准的第一批数据。如果TRIL成功，它将提供一种新的、更合适的护理标准，可在全球范围内使用。

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.