The efficacy and safety of Ojeok-san plus Saengmaek-san for gastro-esophageal reflux-induced chronic cough: a protocol for a pilot, randomized, double-blind, placebo-controlled trial

Abstract Background Gastro-esophageal reflux disease (GERD) is a major cause of chronic cough. GERD-induced chronic cough is difficult to diagnose because some patients do not complain of any gastrointestinal (GI) reflux symptoms. Although chronic cough due to GERD is highly prevalent, no effective treatment is currently available, especially for GERD-related cough without GI symptoms. As the herbal medicines Ojeok-san and Saengmaek-san can effectively treat GERD and cough, we aim to evaluate the efficacy and safety of a combination of these components for relieving chronic cough due to GERD. Methods This is a study protocol of a randomized, double-blind, placebo-controlled, single-center pilot trial. After one-week run-in period, a total of 30 patients with GERD-induced chronic cough will be randomly allocated to an intervention group (n=15) or placebo group (n=15). Participants will receive 5.76 g of Ojeok-san plus Saengmaek-san or a placebo three times per day for 6 weeks. The primary outcome measures, the frequency and severity of cough, will be recorded using a cough diary. The secondary outcome measures will include a cough visual analog scale, the Leicester Cough Questionnaire (Korean version), Gastrointestinal Symptom Rating Scale, Hull Airway Reflux (hypersensitivity) Questionnaire, Pattern Identification for Chronic Cough Questionnaire, Pattern Identification for Gastroesophageal Reflux Disease, and safety testing. Adverse events will also be reported. Discussion This will be the first clinical trial to explore herbal medicines for the GERD-related chronic cough, including patients without GI reflux symptoms. This study will provide useful evidence regarding the efficacy and safety of Ojeok-san plus Saengmaek-san treatment. In addition, this trial will offer scientific basis for the combination of herbal medicines. This finding will also serve as an important data for conducting a larger-scale clinical trial on GERD-induced chronic cough. Trial registration This trial has been registered with Clinical Research Information Service (CRIS) of South Korea (http://cris.nih.go.kr; registration number: KCT0003115). Registered August 28, 2018.