Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)

NCT ID: NCT00441285

Last Updated: 2015-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-09-30

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.

Conditions

Neurocysticercosis; Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

I. ABZ + ABZ Placebo + PZQ

Albendazole 15 mg / kg / d (until 800 mg / d) + Placebo of Albendazole ( 7.5 mg / Kg / d )+ Praziquantel 50 mg / kg / d (until 3600 mg / d)

Group Type: ACTIVE_COMPARATOR

Praziquantel

Intervention Type: DRUG

\- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.

Albendazole

Intervention Type: DRUG

• Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
• Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.

ABZ Placebo

Intervention Type: DRUG

\- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.

II.- ABZ + ABZ Placebo + PZQ Placebo

Albendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )

Group Type: ACTIVE_COMPARATOR

Albendazole

Intervention Type: DRUG

• Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
• Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.

ABZ Placebo

Intervention Type: DRUG

\- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.

PZQ Placebo

Intervention Type: DRUG

\- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.

III .- Albendazole + PZQ Placebo

Albendazole 22.5 mg / kg / d (until 1200 mg / d) + Placebo of Praziquantel ( 50 mg / kg / d )

This arm was not used in the first substudy ( initial part and guide to the design of the parent study ) however it will be used henceforward.

Group Type: ACTIVE_COMPARATOR

Albendazole

Intervention Type: DRUG

• Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
• Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.

PZQ Placebo

Intervention Type: DRUG

\- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.

Interventions

Praziquantel

\- Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.

Intervention Type: DRUG

Albendazole

• Albendazole 15 mg / kg / d ( up to 800 mg /d ) in Arm I for 10 days.
• Albendazole at an increased dose, 22.5 mg / kg / d (up to 1200 mg / d ), in Arm II for 10 days.

Intervention Type: DRUG

ABZ Placebo

\- Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.

Intervention Type: DRUG

PZQ Placebo

\- Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.

Intervention Type: DRUG

Other Intervention Names

PZQ; ABZ; Placebo of Albendazole; Placebo of PZQ

Eligibility Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Universidad Peruana Cayetano Heredia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hector H. Garcia, MD

Role: PRINCIPAL_INVESTIGATOR

Universidad Peruana Cayetano Heredia

E. Javier Pretell, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Alberto

Javier A. Bustos, MD

Role: PRINCIPAL_INVESTIGATOR

Universidad Peruana Cayetano Heredia

Locations

Hospital Nacional Edgardo Rebagliati

Lima, Lima Province, Peru

Hospital Nacional Cayetano Heredia

Lima, Lima Province, Peru

Hospital Nacional Guillermo Almenara

Lima, Lima Province, Peru

Instituto Nacional de Ciencias Neurologicas

Lima, , Peru

Universidad Peruana Cayetano Heredia

Lima, , Peru

Countries

Peru

References

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.

Reference Type: RESULT

PMID: 21332573 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24999157 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26984901 (View on PubMed)

Other Identifiers

R01NS054805

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS054805

Identifier Type: NIH

Identifier Source: org_study_id

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