Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial

Abstract

BackgroundCough is the most reported symptom in the US, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway.Research QuestionWe sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.Study Design and MethodsThis was a randomized, placebo-controlled, parallel design pilot trial of individuals with chronic refractory cough. The effects of six weeks of zinc acetateversusplacebo on quality of life and symptoms as measured by the Cough Quality of Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), Cough Visual Analog Score (C-VAS), and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome.ResultsA total of 34 participants, 17 in each group, were enrolled and randomized. Participants were primarily White females with moderate-severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS, and GACC scores, but the treatment effects of zinc acetateversusplacebo were small with confidence intervals that did not include the MCIDs.InterpretationWe observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.