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NeurocysticercosisPhase 2/3NCT00441285

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

A Phase 2/3 study testing Praziquantel and Albendazole in people with Neurocysticercosis and Epilepsy, run by Universidad Peruana Cayetano Heredia at 5 sites in Peru.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine if combination drug therapy of praziquantel and albendazole is safe and effective to cure neurocysticercosis. Read more about this study

Who is it for?
Ages 16 to 65 years
Conditions the study is for
Neurocysticercosis, Epilepsy
What is being tested?
Praziquantel and Albendazole
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
156 participants
Where
5 sitesPeru
Study dates
Jan 2010to Sep 2013
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Peru5 sites
  • Hospital Nacional Edgardo Rebagliati

    Lima, Lima Province, Lima 11

  • Hospital Nacional Cayetano Heredia

    Lima, Lima Province, Lima 31

  • Hospital Nacional Guillermo Almenara

    Lima, Lima Province, Lima 5

  • Instituto Nacional de Ciencias Neurologicas

    Lima

  • Universidad Peruana Cayetano Heredia

    Lima

Other trials in Peru

About this study

Official title: Antiparasitic Therapy for Neurocysticercosis: Phase II/III Study on Safety and Efficacy of Combined Treatment With Praziquantel and Albendazole

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

Read the 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.

Being tested
Praziquantel, Albendazole, ABZ Placebo, PZQ Placebo
Keywords
neurocysticercosis, NCC, praziquantel, PZQ, albendazole, ABZ, parasite, pig tapeworm, Taenia solium, epilepsy, late-onset epilepsy, acquired epilepsy
Medical subject headings
Neurocysticercosis, Epilepsy, Taeniasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PraziquantelDrug

    Also called PZQ

    • Praziquantel 50 mg / kg / d (up to 3600 mg / d ) for 10 days.
  • AlbendazoleDrug

    Also called ABZ

    • 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 PlaceboDrug

    Also called Placebo of Albendazole

    • Placebo (of Albendazole ) 7.5 mg / kg / d in Arm I and II for 10 days.
  • PZQ PlaceboDrug

    Also called Placebo of PZQ

    • Placebo (of Praziquantel) 50 mg / kg / d in Arm II and III for 10 days.
Study groups in NCT00441285
Study groupRoleWhat they receive
I. ABZ + ABZ Placebo + PZQActive comparatorAlbendazole 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)
Receives: Drug: Praziquantel; Drug: Albendazole; Drug: ABZ Placebo
II.- ABZ + ABZ Placebo + PZQ PlaceboActive comparatorAlbendazole 15 mg / kg / d ( until 800 mg / d ) + Placebo of Albendazole ( 7.5 mg / Kg / d ) + Placebo of Praziquantel ( 50 mg / kg / d )
Receives: Drug: Albendazole; Drug: ABZ Placebo; Drug: PZQ Placebo
III .- Albendazole + PZQ PlaceboActive comparatorAlbendazole 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.
Receives: Drug: Albendazole; Drug: PZQ Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PK Substudy - Area Under the Curve of Albendazole in Treatment in 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).

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose on Treatment day 1

  2. PK Substudy - Area Under the Curve of Albendazole in Treatment Days 10 and 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).

    Measured: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on Treatment days 10-11

  3. PK Substudy - Maximum Concentration of Albendazole

    Highest serum level of Albendazole measured from all level assessments in the curve.

    Measured: Treatment day 1 and Treatment days 10-11

  4. Phase III Trial - Proportion of Patients Without Remaining Live Cysts

    Proportion of patients whose 6 month MR does not show viable parasites anymore

    Measured: Day 180

Secondary outcomes (5)
  1. PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug 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

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 12 hours post dose in treatment day 1

  2. PK Substudy - Area Under the Curve of Praziquantel by Antiepileptic Drug in Treatment Days 10 and 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

    Measured: 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 24 and 36 hours post dose on treatment days 10-11

  3. PK Substudy - Safety of Combined Albendazole Plus Praziquantel Therapy

    • Describe if some Serious Adverse Event was associated to combined Albendazole plus Praziquantel therapy.

    Measured: 90 days post tx

  4. Phase III Trial - Proportion of Cysts Which Resolved

    Proportion of Viable Brain Parasites which Are not Alive Anymore at 6 Months MRI

    Measured: Day 180

  5. Phase III Trial - Seizure Frequency

    Seizure frequency by treatment group

    Measured: Day 1 - 540

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2007 (estimated)
  2. Study startJan 2010
  3. Primary completionDec 2012
  4. Study completionSep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00441285
Sponsor's protocol ID
R01NS054805
Other IDs
R01NS054805
Status last verified
May 2015
First submitted
27 Feb 2007
Last updated
11 Jun 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21332573
  • 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.

    PubMed 24999157
  • 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.

    PubMed 26984901

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Praziquantel and Albendazole in people with Neurocysticercosis and Epilepsy, run by Universidad Peruana Cayetano Heredia at 5 sites in Peru.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Peru. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00441285, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2015.

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