Sub Arachnoid Neurocysticercosis Treatment Outcome (SANTO)

Neurocysticercosis Clinical Trial

— SANTO  

Official title:

A Randomized Trial of Combined Albendazole Plus Praziquantel for Subarachnoid Cysticercosis of the Sylvian Fissure or the Basal Cisterns

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02947581
• Other study ID #: 61449
• Status: Terminated
• Phase: Phase 3
• Start date: November 14, 2016
• Est. completion date: February 27, 2021

Study information

• Verified date: November 2022
• Source: Universidad Peruana Cayetano Heredia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 107
• Est. completion date: February 27, 2021
• Est. primary completion date: August 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• - 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cysticercosis
• Neurocysticercosis

Intervention

Drug:
• Albendazole and praziquantel
Intervention - PZQ (50 mg/k/d, up to 3600 mg/d, for 15 days), as an add-on to ABZ treatment (15 mg/k/d, up to 800 mg/d for days 1-20, up to 1200 mg/d for days 21-30). In order to maintain the double blind nature of the trial, ABZ placebo will be administered to individuals over 53 kg of weight until completing the equivalent doses in the comparison group.
• Albendazole and praziquantel placebo
PZQ placebo in similar doses, given during the initial 15 days of ABZ treatment at standard doses (15 mg/k/d up to 1200 mg/d for 30 days)

Locations

Country	Name	City	State
Peru	Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas	Lima
Peru	Hospital Nacional Cayetano Heredia	Lima

Sponsors (1)

Lead Sponsor	Collaborator
Universidad Peruana Cayetano Heredia

Country where clinical trial is conducted

Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiological efficacy at three months (3-month improvement).	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.	Day 90 +/- 15 days
Secondary	Radiological efficacy at six months (marked improvement or "radiological cure") (evaluated only in patients with improvement at month 3).	Total disappearance or greater than 50% decrease in the combined volume of subarachnoid parasites, evaluated by contrast-enhanced MRI 6 months after therapy onset, and recorded both as a dichotomous outcome and as a continuous quantification. three.months after treatment onset (comparative between treatment arms).	Day 180 +/- 15 days
Secondary	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)	No reappearance or re-growth of the parasitic lesions on contrast enhanced MRI at 12 months after therapy onset, recorded as a dichotomous outcome. hypertension, or progressive neurologic deficits (in cognitive functions, motor function, gait, or other defined neurological signs) in a patient off steroid therapy, as assessed by a study neurologist 12 months post treatment.	Day 365 +/- 15 days
Secondary	Clinically asymptomatic patient	No evidence of uncontrolled seizures, chronic severe headaches, intracranial hypertension, or progressive neurologic deficits (in cognitive functions, motor function, gait, or other defined neurological signs) in a patient off steroid therapy, as assessed by a study neurologist at 3, 6, and 12 months post treatment.	3, 6, and 12 months
Secondary	Decrease in serum levels	will be measured at 3 months, and expressed as a proportion of the baseline level. This variable will be compared between arms	3 months