Fatores associados à adesão a diferentes esquemas de tratamento com antimoniato de meglumina em ensaio clínico para leishmaniose cutânea

O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods

Fatores associados à adesão a diferentes esquemas de tratamento com antimoniato de meglumina em ensaio clínico para Leishmaniose cutânea

Made available in DSpace on 2018-08-13T15:46:52Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) madelon_ribeiro_ipec_mest_2013.pdf: 406392 bytes, checksum: dd6d0734b46be0333d634d142a057a6c (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose (5mg Sb5+/kg/dia) de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.Favorable outcome to the treatment of a disease is influenced by adherence to therapy. We aimed to evaluate factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard treatment regimen and alternate ones with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL) in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods to monitor adherence were used: exceeding vials counting, treatment card monitoring, Morisky test and modified Morisky test (without the question regarding the timetable for taking medication). We observed adherence of 82.1% (returned ampoules), 86.0% (treatment card), 66.7% (Morisky test) and 86.0% (modified Morisky test). Substantial agreement was demonstrated between the method of counting exceeding vials and treatment card monitoring, as well as between that and the modified Morisky test. There was a significant association between higher adherence to treatment and low dose (5mg of the pentavalent antimony / kg / day) of MA, as well as a smaller number of people sleeping in the same room at home. We recommend the use of the modified Morisky test in the evaluation of adherence to treatment of CL with MA as a simple method with good performance when compared to other tests

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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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 <i>Leishmania (Viannia) braziliensis</i> 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: <a href="https://clinicaltrials.gov/ct2/show/NCT01301924" target="_blank">NCT01301924</a>.</p><p>Results</p><p>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<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony.</p><p>Conclusions</p><p>Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.</p></div

Baseline demographic and clinical characteristics of the modified intention-to-treat population.

<p>Baseline demographic and clinical characteristics of the modified intention-to-treat population.</p

Bubble plot of -log10(Raw p-value) by risk difference with a two-sided 95% confidence interval sized by number of subjects with adverse events in high dose versus low dose antimony groups.

<p>Note: Grey zone area corresponds to area of p-value<0.05; X stands for point estimates; point estimates within the grey zone area have p-values<0.05; circles are sized by the number of patients with adverse events; circles located to the right of the vertical solid line favor more adverse events in the high dose antimony group.</p

Different stages of the wound healing process in American cutaneous leishmaniasis.

<p>Different stages of the wound healing process in American cutaneous leishmaniasis.</p

Subgroup analysis: Forest plot of absolute risk difference (RD) and relative risk (RR) with two-sided 95% confidence interval (CI) for major adverse events according to low versus high dose antimony treatment.

<p>Squares located to the right of the vertical solid line favor more major adverse events in the high dose antimony group.</p

Non-inferiority plot of low dose antimony versus high dose antimony for American cutaneous leishmaniasis.

<p>Data are shown as point estimates and 90% confidence interval (CI) for absolute risk difference in clinical cure for intention-to-treat and per-protocol populations. Non-inferiority can be established if confidence intervals are within the prespecified boundary for non-inferiority (Δ).</p