Comparison of the Efficiency of Two Different PPI Formula in Atypical GERD
Comparison of the Efficiency of Two Different PPI Formula in Atypical GERD
Patients with atypical gastro-esophageal reﬂux disease (GERD), include cough, globus, and
 non-cardiac chest pain (NCCP) usually require more aggressive or double dose proton pump
 inhibitor (PPI) therapy than patients with typical GERD. Dexlansoprazole is a new, dual
 delayed release formulation of PPI that increases the mean intragastric pH during a 24-hour
 period. The prospective, open-label, randomized study aims to compare the efficacy of two
 different PPI formula in treating patients with atypical GERD symptoms.

 Patients with atypical GERD symptoms and a total Reflux Symptom Index (RSI) score ≥13 (cough,
 globus, and NCCP) will be invited to participate. Personal characteristics including age,
 sex, body mass index, and the severity of erosive esophagitis will be recorded. After
 enrollment, 120 subjects will randomly assign (at a 1:1 ratio) to receive either oral
 lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexilansoprazole,
 Dexilant 60 mg, once daily before breakfast for 8 weeks. Subjects will record their symptoms
 (cough, globus, NCCP, heart burn, and acid regurgitation) at daytime and nighttime everyday
 via diary for 8 weeks. The primary endpoint is to compare the cumulated incidence of each
 symptom free during 8-week therapy period between the two study groups. The secondary
 endpoint will be the withdrawal or drop-out rate due to poor symptoms response or drug
 adverse effects.

 Data will be analyzed with SPSS Statistical Software for descriptive statistics (percentage,
 mean, standard error, and 95% confidence interval) and analytical statistics (chi-square
 test, ANOVA, and generalized estimation equation; GEE).
We conduct a prospective randomized study since July 2017 after IRB approval. Patients
 between the ages of 20 and 80 years presenting to the gastroenterology outpatient clinic for
 atypical GERD symptoms (cough, globus, and NCCP) with or without typical symptoms (heartburn
 or acid regurgitation) of GERD will be invited to participate. After signing informed
 consents and screening, patients with atypical GERD symptoms for more than one month and with
 a total Reflux Symptom Index (RSI) score ≥13 were eligible for enrollment.Patients who
 currently took pro-kinetic agents, baclofen, antacid, sucralfate, histamin-2 receptor
 antagonists, PPI, antitussive, non-steroid anti-inflammatory drugs, anxiolytics, or
 anti-depressants or takes aforementioned medication during study period, who have severe
 cardiac, pulmonary, hepatic, or renal disease, who have uncured underlying malignancy, will
 be excluded as are subjects with laryngeal or pharyngeal disorders, a history of
 gastrointestinal (GI) surgery, symptoms of GI tract obstruction, or a contraindication for
 PPI use.

 Personal characteristics including age, sex, habit of drinking and smoking, body mass index
 (BMI), waist circumference and underlying co-morbidity including diabetes, hypertension and
 dyslipidemia will be recorded. The findings of esophageal gastroduodenal scopy (EGD) will be
 recorded including the severity of erosive esophagitis (Los Angeles grade A-D or non-erosive
 reflux disease).The symptoms of atypical GERD including cough, globus sensation, and NCCP and
 the symptoms of typical GERD (heart burn and acid regurgitation) will be recorded everyday
 (daytime and night respectively) via diary before PPI therapy for 2 days and after PPI
 therapy for 8 weeks. The definitions of cough, globus sensation, NCCP, heart burn, and acid
 regurgitation will be according to a previous publication After enrollment, 120 subjects will
 randomly assign (at a 1:1 ratio) to receive either oral lansoprazole (Takepron OD 30 mg,
 Takeda Co. Ltd, Tokyo, Japan) once daily before breakfast or oral dexilansoprazole (Dexilant
 60 mg, Takeda Co. Ltd, Tokyo, Japan) once daily before breakfast for 8 weeks. Subjects will
 record their symptoms (cough, globus, NCCP, heart burn, and acid regurgitation) at daytime
 and nighttime everyday for 8 weeks. Symptoms suspecting drug adverse effect including nausea,
 diarrhea, constipation, headache, dizziness, fatigue, flatulence, etc will be recorded for 8
 weeks. Head elevation during sleeping, or on diet for body weight reduction, medication with
 pro-kinetic agents, baclofen, antacid, sucralfate, histamin-2 receptor antagonists, other
 PPI, antitussive, non-steroid anti-inflammatory drugs, anxiolytics, or anti-depressants will
 not be allowed during study period.

 Endpoints We will evaluate the response rate (symptom free) everyday during the 8-week PPI
 therapy for cough, globus sensation, NCCP, acid regurgitation, and heartburn respectively.
 The primary endpoint is to compare the cumulated incidence and the time of each symptom free
 during 8-week therapy period between the two study groups. The secondary endpoint will be the
 withdrawal or drop-out rate due to poor symptoms response or drug adverse effects.
Inclusion Criteria:

 1. atypical GERD symptoms (cough, globus, or NCCP)

 2. with or without typical GERD symptoms (heartburn or acid regurgitation)

 3. A total Reflux Symptom Index (RSI) score ≥13

 Exclusion Criteria:

 1. Patients who currently took pro-kinetic agents, baclofen, antacid, sucralfate,
 histamin-2 receptor antagonists, PPI, antitussive, non-steroid anti-inflammatory
 drugs, anxiolytics, or anti-depressants during screening and during study period

 2. Patients who have severe cardiac, pulmonary, hepatic, or renal diseases

 3. Patients who have uncured underlying malignancy

 4. Patients with laryngeal or pharyngeal disorders

 5. Patients with a history of gastrointestinal (GI) surgery, symptoms of GI tract
 obstruction

 6. Patients with a contraindication for PPI use