Clinical trial NCT00441285: Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)
Official title: Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Neurocysticercosis
Epilepsy
Keywords: neurocysticercosis
NCC
praziquantel
PZQ
albendazole
ABZ
parasite
pig tapeworm
Taenia solium
epilepsy
late-onset epilepsy
acquired epilepsy
Lead sponsor: Universidad Peruana Cayetano Heredia
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2007-02-28
Enrollment: 156
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if combination drug therapy of praziquantel and albendazole is safe and effective to cure neurocysticercosis.

Detailed description: Neurocysticercosis is the single major cause of acquired or late-onset epilepsy in the world, and a common diagnosis in immigrant populations in the United States and other industrialized countries. An estimated 50 million humans are affected by Neurocysticercosis. The disease occurs when a parasite called Taenia solium, or the pig tapeworm, infects the brain, forming cysts. Neurocysticercosis is generally treated with 1 of 2 drugs, praziquantel or albendazole. However, current treatment with either of these drugs alone is not totally effective.

The goal of this trial is to determine if combination drug therapy of praziquantel and albendazole is safe and more effective to cure Neurocysticercosis than either drug administered alone. This trial will consist of two sub-studies and a parent study.

In the first substudy which was performed and completed as the initial part and guide to the design of the parent study, a series of 32 patients with viable cystic intraparenchymal Neurocysticercosis were treated with either albendazole ( 15 mg / kg /d ) + praziquantel ( 50 mg / kg/ d ) or albendazole+Placebo in a double blind randomized study. Half of patients in each group had their seizure disorder treated with phenytoin and the other half with carbamazepine (not assigned by the study). The study was designed and powered for pharmacokinetic evaluation and exploratory safety so comparative cysticidal efficacy has not yet been analyzed. There were no safety concerns. Pharmacokinetics of ABZ and PZQ were obtained and described.

In the parent study, a total of 240 participants ( including the 32 participants from the first substudy ) will be randomly chosen to receive albendazole + praziquantel, albendazole + placebo or albendazole at an increased dose + placebo for 10 days. These groups will also receive other standard medications to manage the disease including appropriate anti-epileptic drug therapy. Participants will stay in the hospital for at least 2 weeks after treatment begins, which includes 5 days after the end of anti-parasitic treatment. After discharge from the hospital, follow-up visits will be on days 21 and 30 after treatment begins, then monthly until day 90, and finally every 3 months until completing 18 months. Brain images will be taken at 6 and 12 months after treatment begins. For participants, duration of the trial is 1 year and a half.

Eligibility criteria: For parent study:

Inclusion Criteria:

* Male or female individuals between 16 to 65 years of age, with a diagnosis of Neurocysticercosis and 20 or less viable cysts.
* Patients with a diagnosis of epilepsy secondary to Neurocysticercosis and a history of one or more spontaneous seizures within the previous year but not longer than 10 years.
* Willingness to complete a minimum of two weeks of hospitalization.
* If female of child bearing potential, negative urine pregnancy testing and willingness to use an adequate method of contraception while on study medications and for at least 3 months following Albendazole therapy.
* Normal laboratory values for hematocrit, platelets, white blood cells and glucose and normal or decreased values for Alanine transaminase, Aspartate transaminase and creatinine.
* Negative PPD measurement and if positive ( \> 9mm induration in the absence of other findings or immunosuppression ) , negative smears for TB.
* Negative fecal exam for Taenia eggs or Strongyloides larvae.

Exclusion Criteria:

* Primary generalized seizures ( e.g., not caused by Neurocysticercosis )
* A history of generalized epileptic status .
* A type of Neurocysticercosis which can expose the patient to increased risk during the study.
* Patients with persistent or progressive symptomatic intracranial hypertension or intracranial hypertension.
* Previous therapy with Albendazole or Praziquantel in the previous year.
* Pulmonary tuberculosis, or symptoms compatible with tuberculosis not otherwise explained.
* Active hepatitis
* Systemic disease that may affect short term prognosis.
* Patients in unstable condition ( consistently abnormal vital signs: body temperature, heart rate, respiratory rate, and blood pressure )
* Pregnancy during antiparasitic treatment
* History of hypersensitivity to Albendazole or Praziquantel
* Concurrent treatment with Cimetidine or Theophylline
* Chronic alcohol or drug abuse
* Unwilling or unable to provide a Computed tomography initially or an Magnetic resonance imaging at 6 months ( as patients with ferromagnetic implants ) , Computed tomography at the end of therapy.
* Unwillingness of subject or legal representative to give written informed consent.

Primary outcomes:
measure: PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1
measure: PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11
measure: PK Substudy - Maximum Concentration of Albendazole
timeFrame: Treatment day 1 and Treatment days 10-11
measure: Phase III Trial - Proportion of Patients Without Remaining Live Cysts
timeFrame: Day 180
Secondary outcomes:
measure: PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1
timeFrame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1
measure: PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11
measure: PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy
timeFrame: 90 days post tx
measure: Phase III Trial - Proportion of Cysts Which Resolved
timeFrame: Day 180
measure: Phase III Trial - Seizure Frequency
timeFrame: Day 1 - 540
Other outcomes:
Locations:
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara
city: Lima
country: Peru
facility: Instituto Nacional de Ciencias Neurologicas
city: Lima
country: Peru
facility: Universidad Peruana Cayetano Heredia
Study officials:
affiliation: Universidad Peruana Cayetano Heredia
name: Hector H. Garcia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Alberto
name: E. Javier Pretell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Peruana Cayetano Heredia
name: Javier A. Bustos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garcia HH, Lescano AG, Lanchote VL, Pretell EJ, Gonzales I, Bustos JA, Takayanagui OM, Bonato PS, Horton J, Saavedra H, Gonzalez AE, Gilman RH; Cysticercosis Working Group in Peru. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis. Br J Clin Pharmacol. 2011 Jul;72(1):77-84. doi: 10.1111/j.1365-2125.2011.03945.x.
citation: Garcia HH, Gonzales I, Lescano AG, Bustos JA, Zimic M, Escalante D, Saavedra H, Gavidia M, Rodriguez L, Najar E, Umeres H, Pretell EJ; Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014 Aug;14(8):687-695. doi: 10.1016/S1473-3099(14)70779-0. Epub 2014 Jul 3.
citation: Garcia HH, Lescano AG, Gonzales I, Bustos JA, Pretell EJ, Horton J, Saavedra H, Gonzalez AE, Gilman RH; Cysticercosis Working Group in Peru. Cysticidal Efficacy of Combined Treatment With Praziquantel and Albendazole for Parenchymal Brain Cysticercosis. Clin Infect Dis. 2016 Jun 1;62(11):1375-9. doi: 10.1093/cid/ciw134. Epub 2016 Mar 16.