Lyu Yee Ran, Kwon O-Jin, Kim Ae-Ran, Kim Min Ji, Lee Yoon Jae, Kim Kwan-Il, Park Jae-Woo, Ko Seok-Jae, Park Yang-Chun, Choi Jun-Yong, Park Tae-Yong, Lee Jun-Hwan, Lee Beom-Joon
Korean Medicine Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
Clinical Medicine Division, R&D Strategy Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
PLoS One. 2025 Jun 25;20(6):e0325786. doi: 10.1371/journal.pone.0325786. eCollection 2025.
Gastroesophageal reflux-induced chronic cough (GERC) is a common extraesophageal manifestation of gastroesophageal reflux disease (GERD). However, the mechanisms underlying GERC remain unclear, and current treatments with anti-reflux drugs do not provide significant benefits in the management of GERC. Therefore, safe and effective drugs to treat GERC are urgently needed.
We designed a randomized, double-blind, placebo-controlled, parallel, multi-center, investigator-initiated clinical trial to assess the efficacy, safety, and economics of combined Ojeok-san (OJS) and Saengmaek-san (SMS) in treating GERC. Our trial will be conducted in five hospitals in Korea, and a total of 138 participants will be enrolled, equally divided between the OJS plus SMS and placebo groups. All participants will be instructed to receive OJS plus SMS or a placebo for 6 weeks and visit hospitals every 2 weeks until week 8 to evaluate their efficacy or safety outcomes. For efficacy outcomes, the cough diary score, cough VAS, Leicester Cough Questionnaire, Gastroesophageal Reflux Disease Questionnaire, Hull Airway Reflux Questionnaire, and 5-level EuroQol 5-dimensional Questionnaire will be evaluated to observe symptoms of cough and GERD, as well as the quality of life in patients with GERC. Pattern identification for the Chronic Cough Questionnaire and gastroesophageal reflux disease will be measured as an additional exploratory outcome. Safety will be assessed in terms of laboratory tests, vital signs, and adverse events; economic evaluation will be simultaneously conducted through the healthcare system and societal perspectives by estimating cost-utility and cost-effectiveness.
Our study proposes a combination of OJS and SMS to manage the symptoms of GERC as a new insight and this study results will provide scientific evidence for the use of OJS plus SMS in the treatment of GERC.
胃食管反流引起的慢性咳嗽（GERC）是胃食管反流病（GERD）常见的食管外表现。然而，GERC的潜在机制仍不清楚，目前使用抗反流药物治疗在GERC的管理中并未带来显著益处。因此，迫切需要安全有效的药物来治疗GERC。
我们设计了一项随机、双盲、安慰剂对照、平行、多中心、研究者发起的临床试验，以评估合枳术散（OJS）和升麻散（SMS）联合治疗GERC的疗效、安全性和经济性。我们的试验将在韩国的五家医院进行，共招募138名参与者，平均分为OJS加SMS组和安慰剂组。所有参与者将被指导接受OJS加SMS或安慰剂治疗6周，每2周前往医院就诊直至第8周，以评估其疗效或安全性结果。对于疗效结果，将评估咳嗽日记评分、咳嗽视觉模拟评分、莱斯特咳嗽问卷、胃食管反流病问卷、赫尔气道反流问卷和5级欧洲五维健康量表，以观察咳嗽和GERD症状以及GERC患者的生活质量。慢性咳嗽问卷和胃食管反流病的模式识别将作为额外的探索性结果进行测量。将通过实验室检查、生命体征和不良事件评估安全性；将通过医疗保健系统和社会视角同时进行经济评估，估计成本效用和成本效益。
我们的研究提出将OJS和SMS联合用于管理GERC症状作为一种新的见解，本研究结果将为使用OJS加SMS治疗GERC提供科学依据。
