Supplementary Material for: Efficacy and safety of GutGard® in managing gastro-esophageal reflux (GER)-related symptoms - A Phase III, single centre, double-blind, randomized placebo-controlled trial

Introduction: Liquorice (Glycyrrhiza glabra) is a traditional herbal remedy with various pharmacological activities mainly used for digestive and respiratory ailments. GutGard® is a flavonoid-rich, deglycyrrhinizated liquorice root extract and is standardized to glabridin (≥3.5% w/w), glabrol (≥0.5% w/w), eicosanyl caffeate (≥0.1% w/w), docosyl caffeate (≥0.1% w/w) and total flavonoids (≥10% w/w) with glycyrrhizin (≤0.5% w/w) as glycyrrhizin causes electrolyte imbalance, hypertension and water retention. . Hence, the objective of the current study was to assess the efficacy, safety and tolerability of GutGard® in managing gastro-esophageal reflux (GER) related symptoms when compared to placebo. Methods: It was a double blind, parallel group, randomized, placebo-controlled trial with participants randomized in a 1:1 ratio to either the placebo group or GutGard® group. The duration of the interventions/treatment was for 28 days and the follow-up visits were done at day-7, day-14, day-28 and day-35. A telephonic follow-up was also done on day-21. The primary outcome measures studied was the change in the Gastroesophageal Reflux Disease – Health Related Quality of Life (GERD- HRQL) and the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS). Results: We screened a total of n=296 participants and enrolled n=200 participants and obtained written, informed consent from them. Participants in the GutGard® group reported a significantly better quality of life at the end of the intervention period (p = 0.014). They also reported earlier resolution of symptoms of GER as against the placebo group especially the symptoms of heartburn (p = 0.017 on day-14 and p = 0.005 on day-28) and regurgitation (p = 0. 025 on day-7, p = 0.029 on day-14 and p = 0.022 on day-28). Conclusions: The GutGard® group showed better and earlier resolution (within two weeks) of symptoms of GER as against the placebo group especially heartburn and regurgitation.