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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.LI

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.

Authors+Show Affiliations

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.Instituto Nacional de Ciencias Neurológicas, Lima, Peru.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.Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru.Bioinformatics Unit, Laboratory of Research and Development, School of Sciences and Philosophy, Universidad Peruana Cayetano Heredia, Lima, Peru.Magnetic Resonance Imaging Center, Resocentro, Lima, Peru.Instituto Nacional de Ciencias Neurológicas, Lima, Peru.Hospital Nacional Edgardo Rebagliati, Essalud, Lima, Peru.Hospital Nacional Guillermo Almenara, Essalud, Lima, Peru.Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Peru.Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Peru.Hospital Nacional Alberto Sabogal, Essalud, Callao, Peru.No affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24999157

Citation

Garcia, Hector H., et al. "Efficacy of Combined Antiparasitic Therapy With Praziquantel and Albendazole for Neurocysticercosis: a Double-blind, Randomised Controlled Trial." The Lancet. Infectious Diseases, vol. 14, no. 8, 2014, pp. 687-695.
Garcia HH, Gonzales I, Lescano AG, et al. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis. 2014;14(8):687-695.
Garcia, H. H., Gonzales, I., Lescano, A. G., Bustos, J. A., Zimic, M., Escalante, D., Saavedra, H., Gavidia, M., Rodriguez, L., Najar, E., Umeres, H., & Pretell, E. J. (2014). Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. The Lancet. Infectious Diseases, 14(8), 687-695. https://doi.org/10.1016/S1473-3099(14)70779-0
Garcia HH, et al. Efficacy of Combined Antiparasitic Therapy With Praziquantel and Albendazole for Neurocysticercosis: a Double-blind, Randomised Controlled Trial. Lancet Infect Dis. 2014;14(8):687-695. PubMed PMID: 24999157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. AU - Garcia,Hector H, AU - Gonzales,Isidro, AU - Lescano,Andres G, AU - Bustos,Javier A, AU - Zimic,Mirko, AU - Escalante,Diego, AU - Saavedra,Herbert, AU - Gavidia,Martin, AU - Rodriguez,Lourdes, AU - Najar,Enrique, AU - Umeres,Hugo, AU - Pretell,E Javier, AU - ,, Y1 - 2014/07/03/ PY - 2014/7/8/entrez PY - 2014/7/8/pubmed PY - 2014/9/16/medline SP - 687 EP - 695 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 14 IS - 8 N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/24999157/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(14)70779-0 DB - PRIME DP - Unbound Medicine ER -