Efficacy, safety, and economic evaluation of Ojeok-san plus Saengmaek-san for gastroesophageal reflux-induced chronic cough: Protocol for a randomized, double-blind, placebo-controlled, parallel, multicenter, investigator-initiated clinical trial.

Abstract

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.