Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. A single-blind...

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Published in:PloS one 2017-05, Vol.12 (5), p.e0178592
Main Authors: Saheki, Mauricio Naoto, Lyra, Marcelo Rosandiski, Bedoya-Pacheco, Sandro Javier, Antônio, Liliane de Fátima, Pimentel, Maria Inês Fernandes, Salgueiro, Mariza de Matos, Vasconcellos, Érica de Camargo Ferreira E, Passos, Sonia Regina Lambert, Santos, Ginelza Peres Lima Dos, Ribeiro, Madelon Novato, Fagundes, Aline, Madeira, Maria de Fátima, Mouta-Confort, Eliame, Marzochi, Mauro Célio de Almeida, Valete-Rosalino, Cláudia Maria, Schubach, Armando de Oliveira
Format: Article
Language:English
Subjects:
Access control
Antimony
Antimony compounds
Benign
Biology and Life Sciences
Brazil
Cadmium
Care and treatment
CD-ROM
Chin
Clinical trials
Complications and side effects
Cost analysis
Cutaneous leishmaniasis
Dermatology
Dosage and administration
Dose-Response Relationship, Drug
Drug development
Drugs
Effectiveness
Epidemiology
Healing
Health care
Humans
Immunology
Infections
Infectious diseases
Intervention
Jaw
Laboratories
Leishmaniasis, Cutaneous - drug therapy
Lesions
Mail
Medical research
Medicine
Medicine and Health Sciences
Meglumine - administration & dosage
Meglumine - therapeutic use
Meglumine antimoniate
Miltefosine
Mucocutaneous leishmaniasis
Mucosa
Ophthalmology
Organometallic Compounds - administration & dosage
Organometallic Compounds - therapeutic use
Otolaryngology
Parasitic diseases
Pharmaceutical industry
Physical Sciences
Poverty
Promastigotes
Public health
Research and Analysis Methods
Risk
Skin
Skin diseases
Surveillance
Tegumentary leishmaniasis
Therapy
Tissues
Ulcers
Vector-borne diseases
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Summary:Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0178592