Hector H Garcia1, Isidro Gonzales2, Andres G Lescano3, Javier A Bustos4, Mirko Zimic5, Diego Escalante6, Herbert Saavedra2, Martin Gavidia7, Lourdes Rodriguez8, Enrique Najar9, Hugo Umeres9, E Javier Pretell10. 1. 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. 2. Instituto Nacional de Ciencias Neurológicas, Lima, Peru. 3. 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. 4. Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru. 5. Bioinformatics Unit, Laboratory of Research and Development, School of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru. 6. Magnetic Resonance Imaging Center, Resocentro, Lima, Peru. 7. Hospital Nacional Edgardo Rebagliati, Essalud, Lima, Peru. 8. Hospital Nacional Guillermo Almenara, Essalud, Lima, Peru. 9. Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Peru. 10. Hospital Nacional Alberto Sabogal, Essalud, Callao, Peru.
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. FINDINGS: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). INTERPRETATION: 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. FUNDING: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.
RCT Entities:
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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.
Authors: T E Nash; G Singh; A C White; V Rajshekhar; J A Loeb; J V Proaño; O M Takayanagui; A E Gonzalez; J A Butman; C DeGiorgio; O H Del Brutto; A Delgado-Escueta; C A W Evans; R H Gilman; S M Martinez; M T Medina; E J Pretell; J Teale; H H Garcia Journal: Neurology Date: 2006-10-10 Impact factor: 9.910
Authors: Hector H Garcia; Andres G Lescano; Vera L Lanchote; E Javier Pretell; Isidro Gonzales; Javier A Bustos; Osvaldo M Takayanagui; Pierina S Bonato; John Horton; Herbert Saavedra; Armando E Gonzalez; Robert H Gilman Journal: Br J Clin Pharmacol Date: 2011-07 Impact factor: 4.335
Authors: Christina M Coyle; Siddhartha Mahanty; Joseph R Zunt; Mitchell T Wallin; Paul T Cantey; A Clinton White; Seth E O'Neal; Jose A Serpa; Paul M Southern; Patricia Wilkins; Anne E McCarthy; Elizabeth S Higgs; Theodore E Nash Journal: PLoS Negl Trop Dis Date: 2012-05-29
Authors: A Clinton White; Christina M Coyle; Vedantam Rajshekhar; Gagandeep Singh; W Allen Hauser; Aaron Mohanty; Hector H Garcia; Theodore E Nash Journal: Clin Infect Dis Date: 2018-11-13 Impact factor: 9.079
Authors: Gianfranco Arroyo; Javier A Bustos; Andres G Lescano; Isidro Gonzales; Herbert Saavedra; Silvia Rodriguez; E Javier Pretell; Pierina S Bonato; Vera L Lanchote; Osvaldo M Takayanagui; John Horton; Armando E Gonzalez; Robert H Gilman; Hector H Garcia Journal: Clin Infect Dis Date: 2019-11-13 Impact factor: 9.079
Authors: A Clinton White; Christina M Coyle; Vedantam Rajshekhar; Gagandeep Singh; W Allen Hauser; Aaron Mohanty; Hector H Garcia; Theodore E Nash Journal: Clin Infect Dis Date: 2018-04-03 Impact factor: 9.079