MEDIDAS DE DESFECHO PRIMÁRIO EM ENSAIOS CLÍNICOS PARA AVALIAÇÃO DA EFICÁCIA DE INTERVENÇÕES NO TRATAMENTO DE ZUMBIDO: UMA REVISÃO DE ESCOPO
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2023-06-28
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Coelho, Cláudia Couto De Barros
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Timmers, Luís Fernando Saraiva Macedo
Picon, Rafael Da Veiga Chaves
Oliveira, Ramatis Birnfeld De
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Múltiplos mecanismos podem estar associados à etiopatogênese do zumbido, como o efeito deletério das espécies reativas de oxigênio sobre o endotélio da microvasculatura que irriga o aparelho auditivo e suas vias de condução neurossensorial. Clinicamente, o zumbido se manifesta como um estímulo sonoro conscientemente percebido, e as particularidades de cada mecanismo fisiopatológico que o origina, por sua vez, refletem na característica sonora referida, que varia de indivíduo para indivíduo. Não por acaso, é experienciado individualmente, especialmente no que se refere à magnitude do impacto na qualidade de vida das pessoas acometidas e o consequente comprometimento funcional destas. Inclusive, instrumentos específicos foram desenvolvidos e validados para avaliar o grau de comprometimento na qualidade de vida dos indivíduos. Em função dessas peculiaridades, da gama de queixas associadas ao sintoma, e da diversidade de mecanismos fisiopatológicos correlacionados à sua etiopatogênese, o delineamento de ensaios clínicos que objetivam a avaliação da eficácia de intervenções para o tratamento de zumbido é um desafio para a pesquisa clínica. Isso explica, em parte, a carência de homogeneidade metodológica na pesquisa clínica de zumbido e, conseguintemente, a variabilidade de abordagens de avaliação da eficácia das intervenções testadas. Dentro deste contexto — e considerando que: i) o uso de substâncias com propriedades antioxidantes ainda é um campo aberto para a pesquisa clínica; ii) a N-acetilcisteína (NAC) é o principal antioxidante endógeno do ser humano, apresentando propriedades otoprotetoras reconhecidas; iii) a necessidade de uniformização no delineamento de ensaios clínicos que avaliem a eficácia terapêutica na pesquisa clínica de zumbido, o presente estudo, em seu objetivo primário, propôs a realização de um ensaio clínico randomizado, triplo-cego, placebo-controlado, para avaliar a eficácia e da NAC no tratamento de zumbido induzido por ruído, quando comparada ao placebo. O ensaio clínico proposto foi aprovado pelo Comitê de Ética em Pesquisa da Universidade de Vale do Taquari e registrado na Plataforma Brasil (Parecer Consubstanciado: 4.810.302). A retomada de sua execução está prevista para 2023. Em seu objetivo secundário, este estudo realizou uma revisão de escopo das principais medidas de desfecho primário utilizadas em ensaios clínicos de avaliação da eficácia de intervenções para o tratamento de zumbido no período 2017-2022. Noventa publicações foram inclusas na revisão. Os instrumentos avaliativos mais utilizados foram o Tinnitus Handicap Inventory, presente em 51% dos estudos; a Visual Analogue Scale, presente em 36% dos estudos; e o Tinnitus Funcional Index, presente em 24% dos estudos. Observou-se, contudo, que um avanço dos padrões para estudos de caráter intervencionista em zumbido ainda não foi alcançado, haja vista que tanto os aspectos de delineamento quanto de relato dos resultados persistem inconsistentes entre as publicações avaliadas. Os resultados desta revisão, dessa forma, podem servir como um alerta para a comunidade de pesquisadores de zumbido, ressaltando, novamente, a necessidade de medidas concretas quanto ao aprimoramento da qualidade metodológica da pesquisa com zumbido e, consequentemente, as chances de progresso no sentido da obtenção de terapias eficazes para o tratamento deste sintoma que impacta na qualidade de vida de milhões de pessoas no mundo todo.
Multiple mechanisms may be associated with the etiopathogenesis of tinnitus, such as the deleterious effect of reactive oxygen species on the endothelium of the microvasculature that irrigates the auditory system and its sensorineural conduction pathways. Clinically, tinnitus manifests as a consciously perceived sound stimulus. The particularities of each pathophysiological mechanism that originates it, in turn, reflect on the referred sound characteristic, which varies from individual to individual. Tinnitus is experienced individually, especially regarding the magnitude of the impact on the quality of life of affected people and their consequent functional impairment. Specific instruments were even developed and validated to assess the degree of impairment in the quality of life of individuals. Due to these peculiarities, the range of complaints associated with the symptom, and the diversity of pathophysiological mechanisms correlated to its etiopathogenesis, the design of clinical trials that aim to evaluate the effectiveness of interventions for the treatment of tinnitus is a challenge for clinical research. This explains, in part, the lack of methodological homogeneity in tinnitus clinical research and, consequently, the variability of approaches to evaluating the effectiveness of the tested interventions. Within this context — and considering that: i) the use of substances with antioxidant properties is still an open field for clinical research; ii) N-acetylcysteine (NAC) is the main endogenous antioxidant in humans, with recognized otoprotective properties; iii) the need for standardization in the design of clinical trials that assess therapeutic efficacy in tinnitus clinical research, the present study, in its primary objective, proposed the performance of a randomized, triple-blind, placebo-controlled clinical trial, to evaluate the efficacy and of NAC in the treatment of noise-induced tinnitus when compared to placebo. The proposed clinical trial was approved by the Research Ethics Committee of the University of Vale do Taquari and registered on the Plataforma Brasil (approval number: 4.810.302). The resumption of its execution is scheduled for 2023. In its secondary objective, this study carried out a scoping review of the main primary outcome measures used in clinical trials evaluating the effectiveness of interventions for the treatment of tinnitus in the period 2017-2022. Ninety publications were included in the review. The most used evaluative instruments were the Tinnitus Handicap Inventory, present in 51% of the studies; the Visual Analogue Scale, present in 36% of the studies; and the Functional Tinnitus Index, present in 24% of the studies. It was observed, however, that an advance in the standards for studies of an interventionist nature in tinnitus has not yet been achieved, given that both aspects of design and reporting of results remain inconsistent among the evaluated publications. The results of this review, therefore, can serve as an alert for the tinnitus research community, emphasizing, once again, the need for concrete measures regarding the improvement of the methodological quality of tinnitus research and, consequently, the chances of progress toward obtaining effective therapies for the treatment of this symptom that impacts the quality of life of millions of people worldwide.
Multiple mechanisms may be associated with the etiopathogenesis of tinnitus, such as the deleterious effect of reactive oxygen species on the endothelium of the microvasculature that irrigates the auditory system and its sensorineural conduction pathways. Clinically, tinnitus manifests as a consciously perceived sound stimulus. The particularities of each pathophysiological mechanism that originates it, in turn, reflect on the referred sound characteristic, which varies from individual to individual. Tinnitus is experienced individually, especially regarding the magnitude of the impact on the quality of life of affected people and their consequent functional impairment. Specific instruments were even developed and validated to assess the degree of impairment in the quality of life of individuals. Due to these peculiarities, the range of complaints associated with the symptom, and the diversity of pathophysiological mechanisms correlated to its etiopathogenesis, the design of clinical trials that aim to evaluate the effectiveness of interventions for the treatment of tinnitus is a challenge for clinical research. This explains, in part, the lack of methodological homogeneity in tinnitus clinical research and, consequently, the variability of approaches to evaluating the effectiveness of the tested interventions. Within this context — and considering that: i) the use of substances with antioxidant properties is still an open field for clinical research; ii) N-acetylcysteine (NAC) is the main endogenous antioxidant in humans, with recognized otoprotective properties; iii) the need for standardization in the design of clinical trials that assess therapeutic efficacy in tinnitus clinical research, the present study, in its primary objective, proposed the performance of a randomized, triple-blind, placebo-controlled clinical trial, to evaluate the efficacy and of NAC in the treatment of noise-induced tinnitus when compared to placebo. The proposed clinical trial was approved by the Research Ethics Committee of the University of Vale do Taquari and registered on the Plataforma Brasil (approval number: 4.810.302). The resumption of its execution is scheduled for 2023. In its secondary objective, this study carried out a scoping review of the main primary outcome measures used in clinical trials evaluating the effectiveness of interventions for the treatment of tinnitus in the period 2017-2022. Ninety publications were included in the review. The most used evaluative instruments were the Tinnitus Handicap Inventory, present in 51% of the studies; the Visual Analogue Scale, present in 36% of the studies; and the Functional Tinnitus Index, present in 24% of the studies. It was observed, however, that an advance in the standards for studies of an interventionist nature in tinnitus has not yet been achieved, given that both aspects of design and reporting of results remain inconsistent among the evaluated publications. The results of this review, therefore, can serve as an alert for the tinnitus research community, emphasizing, once again, the need for concrete measures regarding the improvement of the methodological quality of tinnitus research and, consequently, the chances of progress toward obtaining effective therapies for the treatment of this symptom that impacts the quality of life of millions of people worldwide.
Descrição
Palavras-chave
Zumbido induzido por ruído; N-acetilcisteína; Ensaio clínico randomizado triplo-cego placebo-controlado; Noise-induced tinnitus; N-acetylcysteine; Randomized triple-blind placebo- controlled clinical trial
Citação
SANT'ANA, Wilian Luan Pilatti. MEDIDAS DE DESFECHO PRIMÁRIO EM ENSAIOS CLÍNICOS PARA AVALIAÇÃO DA EFICÁCIA DE INTERVENÇÕES NO TRATAMENTO DE ZUMBIDO: UMA REVISÃO DE ESCOPO . 2022. Dissertação (Mestrado) – Curso de Ciências Médicas, Universidade do Vale do Taquari - Univates, Lajeado, 30 set. 2022. Disponível em: http://hdl.handle.net/10737/3576.