A Randomized Trial of Combined Albendazole Plus Praziquantel for Subarachnoid Cysticercosis of the Sylvian Fissure or the Basal Cisterns
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 107
- 试验地点
- 2
- 主要终点
- Radiological efficacy at three months (3-month improvement).
研究概览
简要总结
Taenia solium neurocysticercosis (NCC) is a parasitic infection causing much neurological disease in most of the world. When parasites locate in the cavities around the brain (subarachnoid NCC, SANCC), it becomes an aggressive, progressive and frequently lethal presentation. Current treatment regimens for SANCC have quite limited efficacy. The investigators propose to compare the current standard of care (a single antiparasitic drug, albendazole) with a combined regimen using two antiparasitic drugs simultaneously by adding praziquantel. The trial will enrol 164 patients in four centers, two in Peru, one in Ecuador, and one in Brasil.
详细描述
Double-blind, randomized, placebo-controlled study in patients with subarachnoid cysticercosis of the basal cisterns or the Sylvian fissure, comparing in two parallel arms the efficacy of the standard of care anti-parasitic regime (30 days of ABZ at 15 mg/k/d, up to 1200 mg/k/d) with a combined regime using similar doses of ABZ and adding PZQ at 50 mg/k/d for the initial 15 days of anti-parasitic treatment. The study and interim analysis plan are designed to allow direct, concrete efficacy comparison in this deadly type of NCC while minimizing the risks of disease progression in the standard of care arm.
In short, this is a parallel group study with a dichotomous primary outcome variable. The main analysis will compare the proportions of patients obtaining the primary outcome at 6 months, using a Chi-square test in a bivariate analysis. A similar analysis will be used for the proportions of patients with a good clinical outcome, and the proportions of patients in whom lesion resolution sustains when assessed at month 12. A Student T test analysis will be used to compare for reduction in parasite volume and non-parametric Mann-Whitney test will be alternatively applied for non-normally distributed data. A non-parametric Spearman's Rho test will be used to assess the correlation between the proportions of cyst mass reduction with the decrease in antigen levels in each study group. A Chi-square test in a bivariate analysis will evaluate the association between negative antigen levels at 6 months versus the complete disappearance of cyst mass.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Tablets containing placebo for PZQ and placebo for ABZ will be purchased from the same commercial sources than those containing active drug if possible. As much as possible, they should have the same size, appearance, excipient, smell, and taste as those containing active drug. A preliminary evaluation of the potential for distinction of active drug and placebo by patients will be performed by the investigators before randomization of the drugs and placebos to their individual coded packages. If distinguishable, a new lot will be ordered.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Male or female adult individuals (18 to 65 y.o.) with a diagnosis of basal subarachnoid cysticercosis (including locations in the Sylvian fissure or lower interhemispheric spaces) by neuroimaging and confirmed by serology.
- •Baseline laboratory results along acceptable ranges (specifically defined in the study protocol).
- •Willingness to accomplish the two-week minimum hospitalization required.
排除标准
- •Previous therapy with ABZ or PZQ in the preceding 3 years (except for patients who received single-dose ABZ for intestinal parasites, or patients who received antiparasitic treatment between one and three years before enrollment but demonstrated lesion persistence or progression during the past 12 months).
- •A type of NCC which can expose the patient to increased risk during the study, specifically: a) intraventricular cysts; b) cysts in brainstem; c) concomitant intraparenchymal lesions greater than 3 cm of diameter in addition to their SANCC lesions; d) more than 20 intraparenchymal cysts in addition to their SANCC lesions; or d) untreated ocular cysticercosis. Patients with a lateral ventricle cyst, less than 2 cm in diameter, without hydrocephalus or intracranial hypertension, can be included. The presence of concomitant intraparenchymal cysts of less than 3 cm in diameter will not exclude the patient unless there are more than 20 of them.
- •Active pulmonary tuberculosis evidenced by positive chest X-ray and positive sputum smears, or symptoms compatible with tuberculosis (fever+sweats or fever+cough) not otherwise explained.
- •Individuals with positive markers for active hepatitis.
- •Systemic disease that may affect therapy or short-term prognosis, including but not limited to chronic renal failure, hepatic insufficiency, cardiac failure, and steroid-dependent immune diseases.
- •Patients in unstable condition or with symptomatic intracranial hypertension (ICH). Definition of symptomatic ICH for this study is the presence of headaches, nausea, and vomiting, with papilledema at fundoscopic examination. Patients in this category can be considered for entrance into the study only after resolution of ICH by ventricular-peritoneal shunting or neuroendoscopic procedures involving CSF flow derivation. These procedures would be done as part of their standard medical care and are not part of the trial intervention.
- •Pregnancy during anti-parasitic treatment. If a patient becomes pregnant after treatment, she will continue in the study but will have radiological exams delayed until after delivery.
- •History of hypersensitivity to ABZ or PZQ
- •Chronic or drug abuse as defined in the study protocol.
- •Unwilling or unable to undergo MRI exams (like patients with ferromagnetic implants)
- •Inability or unwillingness of subject or legal representative to give written informed consent.
研究组 & 干预措施
Interventions
Albendazole and praziquantel. Albendazole: 15 mg/k/d up to 800 mg/d (days 1 to 20), followed by 15 mg/k/d up to 1200 mg/d (day 21 to 30) and prazicuantel (50 mg/k/d days 1 to 15).
干预措施: Albendazole and praziquantel (Drug)
Comparison regime
Albendazole and praziquantel placebo. Albendazole: 15 mg/k/d (days 1 to 30) and prazicuantel placebo in similar doses 50 mg/k/d (days 1 to 15).
干预措施: Albendazole and praziquantel placebo (Drug)
结局指标
主要结局
Radiological efficacy at three months (3-month improvement).
时间窗: Day 90 +/- 15 days
Thirty percent or greater decrease in the combined volume of all parasitic masses, evaluated by contrast-enhanced MRI 3 months after therapy onset, and recorded both as a dichotomous outcome and as a continuous quantification.
次要结局
- Effect persistence at 12 months (no relapse) (evaluated only in patients with marked improvement at month 6) Effect persistence at 12 months (no relapse) (evaluated only in patients with marked improvement at month 6)(Day 365 +/- 15 days)
- Clinically asymptomatic patient(3, 6, and 12 months)
- Radiological efficacy at six months (marked improvement or "radiological cure") (evaluated only in patients with improvement at month 3).(Day 180 +/- 15 days)
- Decrease in serum levels(3 months)