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

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ClinicalTrials.gov Identifier: NCT00441285
Recruitment Status : Completed
First Posted : February 28, 2007
Results First Posted : August 7, 2013
Last Update Posted : June 11, 2015
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Universidad Peruana Cayetano Heredia

Tracking Information
First Submitted Date  ICMJE February 27, 2007
First Posted Date  ICMJE February 28, 2007
Results First Submitted Date  ICMJE January 28, 2010
Results First Posted Date  ICMJE August 7, 2013
Last Update Posted Date June 11, 2015
Study Start Date  ICMJE January 2010
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2013)
  • PK Substudy - Area Under the Curve of Albendazole in Treatment in Day 1 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1 ]
    - To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).
  • PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 11 [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11 ]
    - To evaluate kinetic disposition of Albendazole we calculated the Area under the curve of the active metabolite of Albendazole (Albendazole Sulphoxide) with Praziquantel or Placebo (of Praziquantel).
  • PK Substudy - Maximum Concentration of Albendazole [ Time Frame: Treatment day 1 and Treatment days 10-11 ]
    Highest serum level of Albendazole measured from all level assessments in the curve.
  • Phase III Trial - Proportion of Patients Without Remaining Live Cysts [ Time Frame: Day 180 ]
    Proportion of patients whose 6 month MR does not show viable parasites anymore
Original Primary Outcome Measures  ICMJE
 (submitted: February 27, 2007)
The primary study endpoint is the proportion of parasites that die after one course of antiparasitic therapy (evaluated by contrast-enhanced MRI 6 months after therapy onset) in patients receiving combined ABZ+PZQ therapy compared to ABZ only.
Change History Complete list of historical versions of study NCT00441285 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2013)
  • PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Day 1 [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1 ]
    - To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin
  • PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 11 [ Time Frame: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11 ]
    - To evaluate the kinetic disposition of Praziquantel by antiepileptic drug after the last praziquantel dose, we calculated the Area Under the Curve of Praziquantel with Carbamazepine or Phenytoin
  • PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy [ Time Frame: 90 days post tx ]
    - Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.
  • Phase III Trial - Proportion of Cysts Which Resolved [ Time Frame: Day 180 ]
    Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI
  • Phase III Trial - Seizure Frequency [ Time Frame: Day 1 - 540 ]
    Seizure frequency by treatment group
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neurocysticercosis: Combined Treatment With Praziquantel (PZQ) and Albendazole (ABZ)
Official Title  ICMJE Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Neurocysticercosis
  • Epilepsy
Intervention  ICMJE
  • Drug: Praziquantel
    - Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.
    Other Name: PZQ
  • 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.
    Other Name: ABZ
  • Drug: ABZ Placebo
    - Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
    Other Name: Placebo of Albendazole
  • Drug: PZQ Placebo
    - Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.
    Other Name: Placebo of PZQ
Study Arms  ICMJE
  • Active Comparator: 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)
    Interventions:
    • Drug: Praziquantel
    • Drug: Albendazole
    • Drug: ABZ Placebo
  • Active Comparator: 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 )
    Interventions:
    • Drug: Albendazole
    • Drug: ABZ Placebo
    • Drug: PZQ Placebo
  • Active Comparator: 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.

    Interventions:
    • Drug: Albendazole
    • Drug: PZQ Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 3, 2013)
156
Original Enrollment  ICMJE
 (submitted: February 27, 2007)
180
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Peru
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00441285
Other Study ID Numbers  ICMJE R01NS054805( U.S. NIH Grant/Contract )
R01NS054805 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Universidad Peruana Cayetano Heredia
Study Sponsor  ICMJE Universidad Peruana Cayetano Heredia
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: Hector H. Garcia, MD Universidad Peruana Cayetano Heredia
Principal Investigator: E. Javier Pretell, MD Hospital Alberto
Principal Investigator: Javier A. Bustos, MD Universidad Peruana Cayetano Heredia
PRS Account Universidad Peruana Cayetano Heredia
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP