Efficacy and Tolerability of Zinc Acetate for Treatment of Chronic Refractory Cough: Pilot Randomized Futility Trial
- Aparna Balasubramanian1,
- Janet T. Holbrook2,
- Brendan J. Canning1,
- Loretta G. Que3,
- Mario Castro4,
- Barry J. Make5,
- Linda Rogers6,
- Michael F. Busk7,
- Alexis Rea2,
- Ashley A. McCook-Veal2,
- Jiaxian He2,
- Meredith C. McCormack1 and
- Robert A. Wise1
- on behalf of the American Lung Association Airways Clinical Research Centers
- 1The Johns Hopkins University, School of Medicine, Pulmonary and Critical Care Medicine, Baltimore, MD, USA
- 2The Johns Hopkins University, Bloomberg School of Public Health, Epidemiology, Baltimore, MD, USA
- 3Duke University School of Medicine, Pulmonary, Allergy, and Critical Care Medicine, Durham, NC, USA
- 4Kansas University Medical Center, Pulmonary, Critical Care and Sleep Medicine, Kansas City, KA, USA
- 5National Jewish Health, Division of Pulmonary, Critical Care and Sleep Medicine, Denver, CO, USA
- 6Icahn School of Medicine at Mount Sinai, Pulmonary, Critical Care and Sleep Medicine, NY, NY, USA
- 7St. Vincent Health, Wellness and Preventive Care Institute, Indianapolis, IN, USA
- Corresponding author: Robert Wise (rwise{at}jhmi.edu)
Abstract
Background Cough 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 Question We sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.
Study Design and Methods This was a randomized, placebo-controlled, parallel design pilot trial of individuals with chronic refractory cough. The effects of six weeks of zinc acetate versus placebo 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.
Results A 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 acetate versus placebo were small with confidence intervals that did not include the MCIDs.
Interpretation We 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.
Footnotes
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Conflict of interest: Author M.C. reports grant funding from the NIH, American Lung Association, and PCORI, pharmaceutical grant funding from AstraZeneca, GSK, Novartis, Pulmatrix, Sanofi-Aventis, Shionogi, is a consultant for Genentech, Teva, Sanofi-Aventis, Merck, Novartis, a speaker for for Amgen, AstraZeneca, Genentech, GSK, Regeneron, Sanofi-Aventis, Teva, and receives royalties from Elsevier.
Conflict of interest: Authors A.B., J.T.H, B.J.C, L.G.Q, B.J.M, L.R., M.F.B, A.R, A.A.M, J.H, and M.C.M report no conflicts of interest related to this manuscript.
Conflict of interest: R.A.W reports personal fees for consultation from Merck relevant to the content of this manuscript.
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- Received December 6, 2022.
- Accepted January 13, 2023.
- Copyright ©The authors 2023
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