Open, Randomised, Multi-center Study of on Demand Versus Continuous Esomeprazole Treatment in Patient With GERD

Study Overview
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Brief Summary
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The purpose of this study is to compare on demand with continuous treatment of endoscopy negative subjects with gastroesophageal reflux disease (GERD), with esomeprazole 20-mg once daily, with regards to willingness to continue in the study as a result of satisfactory treatment over a six-month long term management period, after initial symptom relief.

Official Title
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On Demand vs Continuous Treatment of Endoscopy Negative Subjects With Gastroesophageal Reflux Disease (GERD) With Esomeprazole 20-mg Once Daily Over a 6 Months Long Term Treatment Phase. An Open, Randomised, Multicenter Study. NEED.

Conditions
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Gastroesophageal Reflux

Intervention / Treatment
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* Drug: Esomeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms suggestive of GERD, with heartburn as their predominant symptom (described as a burning feeling, rising from the stomach or lower part of the chest up towards the neck), for longer than 6 months. Heartburn occurring for 4 days or more during the last 7 days prior to endoscopy. Or, if PPI treatment has been started within the last 7 days prior to endoscopy, then heartburn occurring for 4 days or more during the last 7 days prior to start of PPI treatment Male or female, at least 18 years of age (for Austria, at least 19 years of age) Have given written informed consent Ability to read and write (literate) 7 symptom free (from heartburn) days in the last week prior to randomisation (day of visit not included) Exclusion Criteria: Documented esophageal mucosal break History of esophageal, gastric or duodenal surgery, except closure and oversewing of an ulcer Chronic or recurrent abdominal pain associated with a chronic or recurrent bowel disturbance and/or bloating, that in the opinion of the investigator is likely to be due to irritable bowel syndrome or two or more of the following criteria: Symptoms relieved by defecation Symptoms associated with change in frequency of stools Symptoms associated with change in form of stools Any significant alarm symptoms such as unintentional weight loss, haematemesis melaena, jaundice or any other sign indicating serious or malignant disease. Subjects with current or historical evidence of the following diseases/conditions Zollinger Ellison syndrome Primary esophageal motility disorder(s) i.e. achalasia, scleroderma, esophageal spasm Complications of GERD such as esophageal stricture, ulcer and/or macroscopic Barrett's metaplasia (longer than 3 centimetres) or significant dysplastic changes in the esophagus Evidence of upper gastrointestinal malignancy at the screening endoscopy Gastric and/or duodenal ulcers within the last 2 years Malabsorption Malignancy, or significant cardiovascular, pulmonary, renal, pancreatic or liver disease as judged by the investigator Unstable diabetes mellitus. Stable diabetes controlled on diet, oral agents or insulin is acceptable Cerebrovascular disease, such as cerebral ischemia, infarction, haemorrhage or embolus Subjects using a PPI for more than 10 days in the last 28 days, prior to endoscopy Use of PPIs for more than 5 days in the last 7 days prior to endoscopy Subjects using daily H2-receptor antagonist, prokinetics recommended in the treatment of reflux symptoms or sucralfate during the 2 weeks prior to endoscopy and between the endoscopy and visit 1 and throughout the study Need for continuous concurrent therapy with NSAIDs (including selective COX II antagonists, salicylates (unless<165 mg daily for cardiovascular prophylaxis) anticholinergics prostaglandin analogues phenytoin ketoconazole itraconazole warfarin and other vitamin K antagonists Pregnancy or lactation. Women of childbearing potential must maintain effective contraception during the study period as judged by the investigator (for Austria: Women of child-bearing potential may only be included when their pregnancy status is assessed by the investigator prior to entry and then at monthly basis. For South-Africa and Spain: Women of child-bearing potential may only be included when their pregnancy status is assessed by the investigator prior to endoscopy) Use of any other investigational compound 28 days prior to start and during the study Requirement of an interpreter (illiterate) Alcohol and/or drug abuse or any condition associated with poor compliance, including expected non-co-operation, as judged by the investigator Previous participation in this study Contra-indications to study drugs, e.g. known or suspected allergy to esomeprazole and any other constituents of the formulation. Known hypersensitivity to substituted benzimidazole

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: On demand 20 mg esomeprazole<br>On demand treatment with 20-mg esomeprazole once daily when needed | Drug: Esomeprazole<br>* Proton pump inhibitor<br>* Other names: Nexium;|
| Active Comparator: Continuous 20 mg esomeprazole<br>Continuous treatment with 20 mg esomeprazole once daily | Drug: Esomeprazole<br>* Proton pump inhibitor<br>* Other names: Nexium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the proportion of patients who discontinued on-demand esomeprazole treatment versus continuous esomeprazole treatment due to unsatisfactory treatment as determined by the investigator in consultation with the patient | Compare on demand (taken as needed by the patient to adequately control their reflux disease) with continuous treatment of endoscopy negative subjects with gastroesophageal reflux disease (GERD), with esomeprazole 20-mg once daily, with regards to willingness to continue in the study as a result of satisfactory treatment over a six-month long term management period, after initial symptom relief | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reasons for discontinuation of on-demand or continuous esomeprazole treatment assessed by investigator-completed questionnaire at clinical visits |  | 6 months | 
| Mean number of esomeprazole tablets taken measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded) |  | 6 months | 
| Change from baseline in impact of reflux symptoms on health-related quality of life using pre-specified dimensions of the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire |  | 6 months | 
| Difference between the proportion of patients reporting treatment satisfaction with on-demand versus continuous esomeprazole treatment assessed by standard patient-completed electronic questionnaire at clinical visits and premature discontinuation |  | 6 months | 
| Frequency of adverse events and assessment of hematology (hemoglobin, leukocytes, thrombocytes) and clinical chemistry (creatinine, alkaline phosphate, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total bilirubin) |  | 6 months | 
| Individual patterns of esomeprazole tablet usage measured using the Medical Event Monitoring System (MEMS) container (date and time of use recorded) |  | 6 months | 
| Change from baseline in impact of reflux symptoms on health-related quality of life using pre-specified dimensions of the Quality Of Life in Reflux And Dyspepsia (QOLRAD) questionnaire |  | 6 months |