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

联合阿苯达唑和吡喹酮治疗蛛网膜下腔 NCC、CCC、铅应用

• 批准号: 9751405
• 负责人: Javier A Bustos
• 金额: $ 36.66万
• 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 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751405
• 关键词: Adverse event; Affect; Aftercare; Albendazole; Antigens; Antiparasitic Agents; Appearance; Area; Brain; Clinical; Complement; Conduct Clinical Trials; Cysticercosis; Data; Developing Countries; Disease; Double-Blind Method; Ecuador; Enrollment; Epilepsy; Fissural; Frequencies; Funding; Growth; Human; Hydrocephalus; Infection; Inflammatory; Intracranial Hypertension; Knowledge; Larva; Lead; Lesion; Magnetic Resonance Imaging; Maintenance; Measures; Microbiology; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neurocysticercosis; Outcome; Parasites; Parasitic infection; Patients; Peru; Praziquantel; Process; Recrudescences; Regimen; Research; Resolution; Safety; Scanning; Seizures; Serious Adverse Event; Serum; Steroids; Symptoms; Taenia solium; Therapeutic; Treatment Protocols; brain tissue; clinical center; clinical efficacy; delta opioid receptor; design; improved; mortality; nervous system disorder; neuroimaging; patient safety; prognostic; public health relevance; quantitative imaging; randomized placebo controlled study; response; secondary outcome; standard of care; treatment duration; treatment effect

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（由申请方提供）：脑囊虫病（NCC）是猪带绦虫幼虫对人类神经系统的感染。蛛网膜下腔脑囊虫病（SANC）占所有NCC病例的20-35%。这是一种侵袭性、渐进性和经常致命的NCC表现，在大多数非穆斯林发展中国家流行。与脑实质内疾病（其中主要表现为癫痫发作和癫痫，寄生虫位于脑组织中）不同，在蛛网膜下腔疾病中，脑周围存在寄生虫团块，它们的生长和伴随的炎症过程导致团块效应、颅内高压和/或脑积水，导致严重的发病率和显著的死亡率，其可超过20%。在SANCC中，抗寄生虫治疗的反应通常是缓慢和部分的，但是如果获得完全的寄生虫消退，则患者可以治愈而没有进一步的症状。 本申请自然扩展了最近NINDS资助的阿苯达唑（ABZ）联合吡喹酮（PZQ）治疗脑实质内NCC试验的范围并应用了该试验获得的知识[R 01 NS 054805]。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显著的死亡率相关。联合使用ABZ和PZQ，沿着适当的类固醇覆盖和其他安全措施，是改善蛛网膜下腔NCC管理的合理下一步，以前没有在对照试验中进行过检查。 在这项双盲、随机化、安慰剂对照研究中，164例基底池或侧裂蛛网膜下腔囊虫病患者将被分配至标准抗寄生虫治疗方案（15 mg/k/d ABZ治疗30天）或在抗寄生虫治疗的最初15天中加入50 mg/k/d PZQ的联合治疗方案。主要研究终点是治疗开始后6个月神经影像学检查中寄生虫病变消失的患者比例。次要结局包括在治疗开始后3个月和6个月通过MRI测量的寄生虫肿块体积的减少，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，与标准治疗相比，联合方案的严重不良事件（SAE）频率，治疗开始后3个月和6个月循环寄生虫抗原血清水平的降低，以及治疗开始后12个月病变消退且未复发的患者比例。 该试验最初将涉及4个中心：2个在秘鲁，1个在巴西，1个在厄瓜多尔，如果需要，可能会扩展到更多的中心。通过比较两种活性治疗方案，拟定的平行组设计允许在不影响治疗设盲的情况下开放评估对照神经影像学扫描的患者安全性，并将提供支持治疗改变或维持标准治疗的首个数据。如果这个试验成功，它将提供一个新的，更合适的护理标准，在世界范围内可用。