Herbal Medicine Maekmundong-Tang on Patients with Nonspecific Chronic Cough: Study Protocol for a Double-Blind, Randomized Controlled Clinical Trial

Abstract

As the treatment of nonspecific chronic cough with conventional medications that treat cough according to the cause is limited, Maekmundong-tang (comprising Liriopis seu Ophiopogonis Tuber, Pinelliae Tuber, Oryzae Semen, Zizyphi Fructus, Ginseng Radix, and Glycyrrhizae Radix et Rhizoma) has been used empirically in the clinical setting of East Asian traditional medicine. This study is the first to explore the feasibility, preliminary effect, safety, and cost-effectiveness of Maekmundong-tang for nonspecific chronic cough. This study protocol is that of a double-blind, randomized, active-controlled, parallel-group clinical trial for comparing Maekmundong-tang with Saengmaek-san (comprising Liriopis seu Ophiopogonis Tuber, Ginseng Radix, and Schisandrae Fructus), a Korean national health insurance-covered herbal medicine for cough. A total of 30 nonspecific chronic cough patients will participate and receive the assigned herbal medicine for 6 weeks, and clinical parameters will be assessed at weeks 0 (baseline), 3 (midterm assessment), 6 (primary endpoint), 9, and 24 (follow-up). Study feasibility outcomes, including recruitment, adherence, and completion rates, will be assessed. Preliminary effects on cough severity, frequency, and quality of life will be evaluated using outcome measures, such as the Cough Symptom Score, Cough Visual Analog Scale, and the Leicester Cough Questionnaire. Adverse events and laboratory tests will be monitored for safety evaluation, and exploratory economic evaluations will be conducted. The results will provide evidence of Maekmundong-tang in the treatment of nonspecific chronic cough.

Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis

“…In particular, the effect of Maekmundong-tang (Maimendong-tang in Chinese), one of the HM, on cough hypersensitivity accompanied by chronic cough has been reported through clinical studies ( Watanabe et al, 2003 ; Watanabe et al, 2004 ). An RCT is also being attempted to explore the effects of Maekmundong-tang on nonspecific chronic cough ( Lee et al, 2023 ). Therefore, in clinical studies evaluating the effect of HM on chronic cough in the future, the cause of the cough should be reported if known, or it should be specified as an explained or nonspecific chronic cough based on the definition in the guideline ( Gibson et al, 2016 ; Song et al, 2018 ).…”

“…HM especially has the potential to be a treatment for nonspecific or unexplained chronic cough as well as specific coughs based on the characteristics of multi-components and multi-targets ( Wang et al, 2012 ). Accordingly, clinical trials to evaluate the effects of specific HMs on nonspecific chronic cough are being conducted ( Kim et al, 2016 ; Lee et al, 2023 ). Although the effects of HM were previously summarized through systematic reviews, these were mainly limited to common causes of chronic cough, such as CVA and UACS ( Jiang et al, 2016 ; Chen et al, 2021 ).…”