title: Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial.
abstract: BACKGROUND
  Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations.
  
  
  METHODS
  In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285.
  
  
  RESULTS
  Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group).
  
  
  CONCLUSIONS
  Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis.
  
  
  BACKGROUND
  National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.
authors.affiliation: Instituto Nacional de Ciencias Neurológicas, Lima, Peru; Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru; Center for Global Health Tumbes, Universidad Peruana Cayetano Heredia, Lima, Peru. Electronic address: hgarcia@jhsph.edu.
authors.forename: Hector H
authors.initials: HH
authors.lastname: Garcia
authors.affiliation: Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
authors.forename: Isidro
authors.initials: I
authors.lastname: Gonzales
authors.affiliation: School of Public Health, Universidad Peruana Cayetano Heredia, Lima, Peru; Department of Parasitology and Public Health Training Program, US Naval Medical Research Unit No 6 (NAMRU6), Callao, Peru.
authors.forename: Andres G
authors.initials: AG
authors.lastname: Lescano
authors.affiliation: Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Bustos
authors.affiliation: Bioinformatics Unit, Laboratory of Research and Development, School of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
authors.affiliation: Magnetic Resonance Imaging Center, Resocentro, Lima, Peru.
authors.forename: Diego
authors.initials: D
authors.lastname: Escalante
authors.affiliation: Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
authors.forename: Herbert
authors.initials: H
authors.lastname: Saavedra
authors.affiliation: Hospital Nacional Edgardo Rebagliati, Essalud, Lima, Peru.
authors.forename: Martin
authors.initials: M
authors.lastname: Gavidia
authors.affiliation: Hospital Nacional Guillermo Almenara, Essalud, Lima, Peru.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Peru.
authors.forename: Enrique
authors.initials: E
authors.lastname: Najar
authors.affiliation: Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Peru.
authors.forename: Hugo
authors.initials: H
authors.lastname: Umeres
authors.affiliation: Hospital Nacional Alberto Sabogal, Essalud, Callao, Peru.
authors.forename: E Javier
authors.initials: EJ
authors.lastname: Pretell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015766:Albendazole / Q000009:adverse effects / Q000627:therapeutic use*; D000871:Anthelmintics / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020019:Neurocysticercosis / Q000188:drug therapy*; D010919:Placebos / Q000008:administration & dosage; D011223:Praziquantel / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D010919:Placebos; D011223:Praziquantel; D015766:Albendazole