Sub Arachnoid Neurocysticercosis Treatment Outcome (SANTO)

NCT02947581 | Terminated Phase 3 DMC

• 1 other identifier: 61449
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Neurocysticercosis

Keywords

subarachnoid neurocysticercosis; albendazole; praziquantel

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Radiological efficacy at six months (marked improvement or "radiological cure") (evaluated only in patients with improvement at month 3).

  Day 180 +/- 15 days

• 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

• Decrease in serum levels

  3 months

Study Arms (2)

Interventions

EXPERIMENTAL

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).

Drug: Albendazole and praziquantel

Comparison regime

ACTIVE COMPARATOR

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).

Drug: Albendazole and praziquantel placebo

Interventions

Albendazole and praziquantel DRUG

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.

Also known as: ABZ+PZQ

Interventions

Albendazole and praziquantel placebo DRUG

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)

Also known as: ABZ+PZQ PCB

Comparison regime

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad Peruana Cayetano Heredia: lead

Study Sites (2)

Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas

Lima, Lima 1, Peru

Location

Hospital Nacional Cayetano Heredia

Lima, Peru

Location

MeSH Terms

Conditions

Neurocysticercosis

Interventions

Albendazole; Praziquantel

Condition Hierarchy (Ancestors)

Central Nervous System Helminthiasis; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Cysticercosis; Taeniasis; Cestode Infections; Helminthiasis; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoquinolines

Study Officials

• Hector H. Garcia Lescano, Ph.D

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: October 28, 2016
• Study Start: November 14, 2016
• Primary Completion: August 21, 2020
• Study Completion: February 27, 2021
• Last Updated: November 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Available: December 2021, until December 2023
• Access Criteria: The information will be shared upon requested by interested researchers

Locations

PE (2)