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: 9134908
• 负责人: Hector Hugo Garcia
• 金额: $ 42.27万
• 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/9134908
• 关键词: Accounting; 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; Frequencies; Funding; Growth; Health; Human; Hydrocephalus; Infection; Inflammatory; 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; Outcome; Parasites; Parasitic infection; Patients; Peru; Praziquantel; Process; Recrudescences; Regimen; Relapse; Research; Resolution; Safety; Scanning; Seizures; Serious Adverse Event; Serum; Staging; Steroids; Symptoms; Taenia solium; Therapeutic; Treatment Protocols; brain tissue; clinical efficacy; control trial; design; improved; mortality; nervous system disorder; neuroimaging; patient safety; prognostic; quantitative imaging; randomized placebo controlled trial; 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（由申请人提供）：神经囊虫病（NCC）是猪肉tapeworm taenia solium的幼虫对人类神经系统的感染。蛛网膜下腔神经囊肿（SANCC）占所有NCC病例的20-35％。这是对NCC的一种积极进取，进步且经常致命的表现，在大多数非穆斯林发展中国家中流行。与核内疾病（主要表现是癫痫发作和癫痫病，以及寄生虫位于脑组织中），在蛛网膜下腔疾病中，大脑周围的寄生质量存在，其生长，它们的生长以及炎症过程会导致质量较大的疾病，从而产生了巨大的疾病，从而导致了高度的高度和氢化性，从而导致了高度含量，从而导致了高度含量，并导致高含量，造成了脑力的疾病，并导致高度渗透性，并导致高度渗透性，并导致高度渗透性，并导致高度含量，并导致高度含量，并导致高度含量，并导致脑中的高度含量，并导致脑电图症20％。在SANCC中对抗寄生虫治疗的反应通常是缓慢而部分的，但是如果获得了完全寄生虫，则可以治愈患者，而无需进一步的症状。 该应用自然扩大了从NINDS资助的Arbendazole（ABZ）加上Praziquantel（PZQ）治疗核内核内NCC [R01 NS054805]的近期试验中获得的知识[R01 NS054805]。当前的SANCC治疗方案的疗效非常有限，在许多地方，该疾病仍然与死亡率显着有关。将ABZ和PZQ与适当的类固醇覆盖范围和其他安全措施相结合，是改善蛛网膜下腔NCC管理的逻辑下一步，并且在对照试验中之前尚未对其进行检查。 在这项双盲，随机，安慰剂对照的研究中，将有164例基础蓄水池的蛛网膜下腔病或Sylvain Fissure患者分配给护理抗寄生状态的标准（以15 mg/k/d为例30天ABZ）或在50 mg/ks/ks的联合治疗中以50 mg/k/d的合并状态为50 mg/d添加。主要研究终点是在治疗后六个月内神经影像学中寄生病变消失的患者的比例。次要结局包括在治疗开始后3和6个月测量的MRI测量的寄生质量的体积减少，临床改善是无症状的患者比例，无需进一步的抗寄生虫治疗，治疗后6个月，严重不良事件的频率（SAE）在3个月后的循环均降低，与循环的循环降低，循环降低了循环，相比之下。发作，病变可以解决并且在治疗发作后12个月后不会复发的患者比例。 该试验最初将涉及四个中心：秘鲁两个中心，一个在巴西，一个在厄瓜多尔，有可能在需要时扩展到更多中心。通过比较两个主动制度，提出的平行组设计允许对控制神经影像扫描进行公开评估患者安全，而不会影响治疗失明，并将提供第一个数据以支持治疗性更改或维护护理标准。如果这个三角形成功，它将提供全球可用的新的，更合适的护理标准。