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Sub Arachnoid Neurocysticercosis Treatment Outcome (SANTO) (SANTO)

Primary Purpose

Neurocysticercosis

Status
Terminated
Phase
Phase 3
Locations
Peru
Study Type
Interventional
Intervention
Albendazole and praziquantel
Albendazole and praziquantel placebo
Sponsored by
Universidad Peruana Cayetano Heredia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurocysticercosis focused on measuring subarachnoid neurocysticercosis, albendazole, praziquantel

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas
  • Hospital Nacional Cayetano Heredia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Interventions

Comparison regime

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.
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.
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

Full Information

First Posted
October 24, 2016
Last Updated
November 11, 2022
Sponsor
Universidad Peruana Cayetano Heredia
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1. Study Identification

Unique Protocol Identification Number
NCT02947581
Brief Title
Sub Arachnoid Neurocysticercosis Treatment Outcome (SANTO)
Acronym
SANTO
Official Title
A Randomized Trial of Combined Albendazole Plus Praziquantel for Subarachnoid Cysticercosis of the Sylvian Fissure or the Basal Cisterns
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Albendazole and albendazole placebo are not available in our local suppliers or in the international market. Consequently, it is no possible to re-initiate the enrollment to complete the original sample size.
Study Start Date
November 14, 2016 (Actual)
Primary Completion Date
August 21, 2020 (Actual)
Study Completion Date
February 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universidad Peruana Cayetano Heredia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurocysticercosis
Keywords
subarachnoid neurocysticercosis, albendazole, praziquantel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model 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.
Masking
ParticipantInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
107 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interventions
Arm Type
Experimental
Arm Description
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).
Arm Title
Comparison regime
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Albendazole and praziquantel
Other Intervention Name(s)
ABZ+PZQ
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Albendazole and praziquantel placebo
Other Intervention Name(s)
ABZ+PZQ PCB
Intervention Description
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)
Primary Outcome Measure Information:
Title
Radiological efficacy at three months (3-month improvement).
Description
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.
Time Frame
Day 90 +/- 15 days
Secondary Outcome Measure Information:
Title
Radiological efficacy at six months (marked improvement or "radiological cure") (evaluated only in patients with improvement at month 3).
Description
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).
Time Frame
Day 180 +/- 15 days
Title
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)
Description
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.
Time Frame
Day 365 +/- 15 days
Title
Clinically asymptomatic patient
Description
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.
Time Frame
3, 6, and 12 months
Title
Decrease in serum levels
Description
will be measured at 3 months, and expressed as a proportion of the baseline level. This variable will be compared between arms
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hector H. Garcia Lescano, Ph.D
Organizational Affiliation
Universidad Peruana Cayetano Heredia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas
City
Lima
ZIP/Postal Code
Lima 1
Country
Peru
Facility Name
Hospital Nacional Cayetano Heredia
City
Lima
Country
Peru

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized patient data will be shared upon request and review by the project leaders.
IPD Sharing Time Frame
Available: December 2021, until December 2023
IPD Sharing Access Criteria
The information will be shared upon requested by interested researchers

Learn more about this trial

Sub Arachnoid Neurocysticercosis Treatment Outcome (SANTO)

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