Oxfendazole in Mild Parenchymal Brain Cysticercosis

Phase 3Not Yet RecruitingNCT06565507

Universidad Peruana Cayetano Heredia544 enrolled

Overview

The goal of this clinical trial is to compare a single and multiple dose regimens of oxfendazole with the standard treatment in patients with mild (one or two lesions) parenchymal brain cisticercosis. The main question it aims to answer is if OXF will enhance clearance of brain parasites and therefore provide greater cysticidal efficacy, with the potential to provide a single-dose therapy for this type of NCC. The study cohort will also allow us to identify early imaging markers that predict lesion resolution, as well as factors associated with residual calcification or focal gliosis after lesion resolution. This study will also provide additional information on the safety of the study interventions.

This three-arm randomized controlled phase II/III clinical trial will compare the efficacy and safety of a single-dose regimen with 20 mg/kg oxfendazole and a regimen with three similar doses spread over seven days (day 1, day 4 and day 7), with the most effective antiparasitic regimen available, combined albendazole plus praziquantel for ten days in individuals with mild NCC (with one to two lesions). Participants will receive treatment with oxfendazole (one or three dose regimens) or the standard treatment (albendazole + praziquantel). At day 15 after treatment onset, an MRI will be perfomed to evaluate early predictors of lesion resolution. MRI at day 90 will serve to evaluate efficacy (lesion resolution) and a day 180 MRI will evaluate sequelar lesions. CT will be perfomed at the en of the study to confirm persistence of calcified sequelar lesion. The study will enroll 544 patients with viable or degenerating parenchymal NCC with no more than two lesions, all in a single brain area. Lesions can be one or two adjacent, viable or degenerating NCC lesions. Patients with only calcified lesions will not be included even if they show perilesional contrast enhancement.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Interventions

Oxfendazole single doseDRUG

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, as a single dose. Oxfendazole placebo will be used at days 4 and 7 to maintain blinding between the two intervention arms.

Oxfendazole three dosesDRUG

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, in three days (1, 4 and 7)

albendazole plus praziquantel regimeDRUG

Subjects will receive a combination of albendazole plus praziquantel, as a standard treatment for brain cysticercosis (neurocysticercosis), orally, for ten days. Albendazole will be given at 15/kg/d and praziquantel at 50/kg/d.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female individuals between 12 and 75 years of age, with suspected viable or degenerating intraparenchymal brain cysticercosis on neuroimaging (CT or MRI) and fulfill the diagnostic criteria for solitary cysticercus granuloma (Rajshekhar and Chandy, 1997) 2. If female of child-bearing potential and men, willing to use an adequate method of contraception\*, including implants, injectables, combined oral contraceptives, effective intrauterine devices, sexual abstinence, or vasectomized partner while participating in the study. 3. Patients with normal laboratory values for hemoglobin, platelet counts, total white blood cells, glucose, creatinine, bilirubin, ALT, and AST. 4. Availability to grant informed consent if you are over 18 years of age or assent if you are a minor between 12 and 17 years of age. Exclusion Criteria: 1. Multiple lesion sites or more than two adjacent lesions. 2. Suspected neurotuberculosis (Rajshekhar's criteria) \[66,67\] 3. More than two viable brain cysts. 4. Large brain cysts (\> 3cm in diameter) 5. Subarachnoid neurocysticercosis or intraventricular 6. Untreated ocular cysticercosis 7. Previous therapy with ABZ (does not include patients who received single-dose 400 mg ABZ for intestinal parasites), or PZQ in the past twelve months. 8. Active pulmonary tuberculosis evidenced by a positive chest X-ray and positive sputum smears. 9. Systemic disease other than NCC 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. 10. Patients in unstable condition or with severe intracranial hypertension (ICH). Definition of severe ICH for this study would be the presence of headaches, nausea, and vomiting, and papilledema at fundoscopic examination. 11. Pregnancy 12. History of hypersensitivity to ABZ or PZQ 13. Concurrent treatment with cimetidine, ranitidine, or theophylline. 14. Chronic alcohol or drug abuse 15. Positive to Strongyloides infection 16. History of reported allergy to contrast substances used in MRI.

Outcomes

Primary Outcomes

Efficacy: completely resolution or persistance only as small lesion remnants.

Proportion of participants whose lesions completely resolved or persist only as small lesion remnants (\<20% of the original lesion size).

Time frame: Three months after treatment onset

Secondary Outcomes

Clinical effectiveness: Seizure relapses.

The frequency of seizure relapses in individuals whose lesions resolved compared to those who had remaining viable or degenerating lesions on month 3 MRI

Time frame: In the initial 12 months after treatment

Safety: Serious adverse events

Proportion of participants in each group who develop serious or severe adverse events, and the numbers of adverse events per group