Efficacy and Safety of Sodium Alginate Oral Suspension to Treat Non-erosive Gastro-esophageal Reflux Disease

Study Overview
=================
Brief Summary
-----------------
About 60% of patients with typical gastroesophageal reflux symptoms such as heartburn and regurgitation are considered to have non-erosive reflux disease (NERD). Patients with NERD show an overall poorer response to PPI treatment than patients with erosive reflux disease. Sodium alginate oral suspension is a medication indicated for the relief of gastroesophageal reflux symptoms. This multi-center, double blind, randomized trial aims to compare the efficacy and safety profiles of sodium alginate oral suspension (50 mg/ml) 20 ml three times daily with that of omeprazole (20 mg/capsule) 1 capsule once daily for the treatment of NERD patients in Taiwan. Efficacy assessments include percentage of patients achieving adequate relief of heartburn or regurgitation after 4 weeks treatment, improvement of reflux symptoms as assessed by reflux disease questionnaire before and after treatment, and patients overall satisfaction at the end of study. Safety assessments include incidence of adverse events and change of the laboratory test results. The study hypothesis is that treatment with sodium alginate is non-inferior to omeprazole in relieving heartburn or regurgitation symptoms of the NERD patients.

Detailed Description
-----------------
This multi-center, double blind, randomized trial aims to compared the efficacy and safety profiles of sodium alginate oral suspension (50 mg/ml) 20 ml three times daily with that of omeprazole (20 mg/capsule) 1 capsule once daily for the treatment of non-erosive reflux disease (NERD) patients in Taiwan. Patients will be included into study if they are diagnosed as NERD; with heartburn or regurgitation (either one) as main symptom at least 2 days a week and had been present for ≧1 month before screening; with heartburn or regurgitation (either one) during the 7 days screening period, either with frequency for ≧4 days of mild symptom, or ≧ 2 days of moderate to severe symptom; and have signed the informed consent. Patients will be excluded if they are diagnosed as erosive gastroesophageal reflux disease (GERD), Barrett's esophagus or esophageal stricture; with active or healing gastroduodenal ulcer (except scars); with history of gastric, duodenal or esophageal surgery; with intrahepatic stone, gallstone, gallbladder sludge, hepatic or pancreatic carcinoma as evidenced by abdominal ultrasonography, with ischemic heart disease as evidenced by electrocardiogram; taking a proton pump inhibitor (PPI) within 14 days before screening, or a H2-blocker, prokinetic agent or antacid within 7 days before screening; or with clinically significant liver or kidney disease. The primary efficacy endpoint is percentage of patients achieving adequate heartburn (defined as a burning feeling or pain behind the breast bone) or regurgitation (defined as an acid taste in the mouth or unpleasant movement of material upwards from the stomach) relief at day 28 as assessed by patient diary. The secondary efficacy endpoints are percentage of patients achieving adequate heartburn or regurgitation relief at day 14; change from baseline of the reflux disease questionnaire total score at day 14 & 28; patients' overall satisfaction at the end of study; and number of antacid used during the 4-week treatment period. The safety endpoints are incidence of adverse events, and changes in laboratory test results (hematology, biochemistry, and urinalysis). The study hypothesis is that treatment with sodium alginate is non-inferior to omeprazole in relieving heartburn or regurgitation symptoms of the NERD patients.

Official Title
-----------------
A Multi-center, Double-blind, Randomized, Parallel Study to Evaluate the Efficacy and Safety of Sodium Alginate Oral Suspension (50 mg/ml) in Comparison to Omeprazole (20 mg/Cap) to Treat Non-erosive Gastro-esophageal Reflux Disease (NERD)

Conditions
-----------------
Gastroesophageal Reflux Disease, Heartburn

Intervention / Treatment
-----------------
* Drug: Sodium alginate
* Drug: Omeprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with age of 20-75 years old (inclusive) in Taiwan of both genders Out-patients who had been diagnosed as non-erosive gastroesophageal reflux disease (NERD) Patients with heartburn or regurgitation (either one) as main symptom at least 2 days a week and had been present for > or = 1 month before screening Patients with heartburn or regurgitation (either one) during the 7 days screening period, either with frequency for > or = 4 days of mild symptom, or for > or = 2 days of moderate to severe symptom Patients have signed the informed consent form Exclusion Criteria: Patients with erosive gastroesophageal reflux disease (GERD), Barrett's esophagus or esophageal stricture Patients with active or healing gastroduodenal ulcer (except scars) Patients with history of gastric, duodenal or esophageal surgery Patients with malignant disease of any kind Patients with intrahepatic stone, gallstone, gallbladder sludge, hepatic or pancreatic carcinoma as evidenced by abdominal ultrasonography Patients with ischemic heart disease as evidenced by electrocardiogram Female patients who are pregnant or nursing mother Patients with a history of allergy to any of the study drugs or their related compounds Patients with a history of alcohol or drug abuse Patients with clinically significant liver disease (aspartate aminotransferase (AST), alanine aminotransferase (ALT)>2 upper limits of normal) Patients with clinically significant renal disease (serum creatinine >1.5 mg/dl) Patients taken a proton pump inhibitor (PPI) within 14 days before screening, or a H2-blocker, prokinetic agent or antacid within 7 days before screening Patients participated any investigational drug trial within 4 weeks before screening Patients with any other conditions or diseases that investigator considers it is not appropriate to enter the study

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium alginate<br>Oral suspension, 50 mg/ml | Drug: Sodium alginate<br>* oral suspension, 50 mg/ml, 20 ml three times daily, 4 weeks<br>* Other names: Alginos;|
| Active Comparator: Omeprazole<br>20 mg/cap | Drug: Omeprazole<br>* 20 mg capsule, 1 capsule once daily, 4 weeks<br>* Other names: Omelon;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving adequate heartburn or regurgitation relief at day 28 as assessed by patient diary | Adequate heartburn or regurgitation relief is defined as no more than 1 day of mild heartburn or regurgitation episodes in the last 7 days before day 28 | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving adequate heartburn or regurgitation relief at day 14 as assessed by patient diar | Adequate heartburn or regurgitation relief is defined as no more than 1 day of mild heartburn or regurgitation episodes in the last 7 days before day 14 | 2 weeks | 
| Change from baseline of the Reflux Disease Questionnaire (RDQ) total score at days 14 & 28 | RDQ is a 12-item self-administered questionnaire and there are 3 subscales that evaluate frequency and severity of heartburn, regurgitation and dyspepsia. Each item is scored on a 6-point Likert scale ranging from 0 to 5. The RDQ total scores are determined by the sum of 12-item scores. | 2 and 4 weeks | 
| Patients' overall satisfaction at the end of study | The overall satisfaction is categorized as:0=very poor; 1=poor; 2=unsatisfactory; 3=satisfactory; 4=good; 5=very good | 4 weeks | 
| Number of antacid used during the treatment period |  | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alginate, Gastroesophageal reflux disease