Esomeprazole (NEXIUM) vs. Surgery

Study Overview
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Brief Summary
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The study investigates the efficacy of long-term treatment of esomeprazole compared to anti-reflux surgery in the control of gastroesophageal reflux disease by assessing time to treatment failure.

Official Title
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An Open, Randomized, Multicenter, Phase IIIB Study During 5 Years to Assess Long-term Efficacy and Tolerability of Esomeprazole Compared to Laparoscopic Anti-reflux Surgery in Adult Subjects With Gastroesophageal Reflux Disease - LOTUS.

Conditions
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Gastroesophageal Reflux

Intervention / Treatment
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* Drug: esomeprazole
* Procedure: Laparoscopic fundoplication (surgery)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects considered suitable for surgical treatment and long-term management of esomeprazole. History of chronic reflux esophagitis or symptomatic GERD Exclusion Criteria: History of esophageal, gastric, or duodenal surgery predicted to influence negatively on subsequent treatment within the study. Contraindication to the study drug. Pregnancy, lactating or of child-bearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Active Comparator: 1<br>Surgery | Procedure: Laparoscopic fundoplication (surgery)<br>* Surgery<br>|
| Experimental: 2<br>Esomeprazole (NEXIUM) therapy | Drug: esomeprazole<br>* 40 mg oral tablet administered daily<br>* Other names: Nexium®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Failure at 5 Years | Treatment failure in the surgical arm defined when need for medical treatment for control of symptoms from reflux disease. Treatment failure in the medical arm defined when need for treatment other than esomeprazole for control of symptoms of reflux disease. | During 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Los Angeles (LA) Grade 'Normal' at 5 Year Visit | Endoscopic findings classified according to the Los Angeles classification: Grade Normal - endoscopy reveals no mucosal break Grade A- one or more mucosal breaks <5 mm in maximal length Grade B - one or more mucosal breaks >5 mm, but without continuity across mucosal folds Grade C - Mucosal breaks continuous between >2 mucosal folds, but involving less than 75% of the esophageal circumference Grade D - Mucosal breaks involving more than 75% of the esophageal circumference | At 5 year visit | 
| Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn | Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe) Participants with no heartburn | At 5 year visit | 
| Total Score for Microscopic Reflux-related Changes in the Distal Esophagus 2 cm Above the Z-line, at 5 Year Visit | The total score expressed as a mean of all the scores/number of lesions assessed; scored 2 when erosion/necrosis is found. The score could range from 0 to 2 (maximum severity). Only participants with biopsy at 5 years visit included | At 5 year visit | 
| Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit | Intra-gastric acid exposures assessed by 24-h pH-metry. Only participants with pH-emtry performed at 5 year visit included | At 5 year visit | 
| Los Angeles (LA) Grade 'A' at 5 Year Visit | Endoscopic findings classified according to the Los Angeles classification: Grade Normal - endoscopy reveals no mucosal break Grade A- one or more mucosal breaks <5 mm in maximal length Grade B - one or more mucosal breaks >5 mm, but without continuity across mucosal folds Grade C - Mucosal breaks continuous between >2 mucosal folds, but involving less than 75% of the esophageal circumference Grade D - Mucosal breaks involving more than 75% of the esophageal circumference | At 5 year visit | 
| Los Angeles (LA) Grade 'B' at 5 Year Visit | Endoscopic findings classified according to the Los Angeles classification: Grade Normal - endoscopy reveals no mucosal break Grade A- one or more mucosal breaks <5 mm in maximal length Grade B - one or more mucosal breaks >5 mm, but without continuity across mucosal folds Grade C - Mucosal breaks continuous between >2 mucosal folds, but involving less than 75% of the esophageal circumference Grade D - Mucosal breaks involving more than 75% of the esophageal circumference | At 5 year visit | 
| Los Angeles (LA) Grade C at 5 Year Visit | Endoscopic findings classified according to the Los Angeles classification: Grade Normal - endoscopy reveals no mucosal break Grade A- one or more mucosal breaks <5 mm in maximal length Grade B - one or more mucosal breaks >5 mm, but without continuity across mucosal folds Grade C - Mucosal breaks continuous between >2 mucosal folds, but involving less than 75% of the esophageal circumference Grade D - Mucosal breaks involving more than 75% of the esophageal circumference | At 5 year visit | 
| Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn | Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with mild heartburn | At 5 year visit | 
| Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn | Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with moderate heartburn | At 5 year visit | 
| Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn | Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with severe heartburn | At 5 year visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acid reflux disease, Gastroesophageal Reflux Disease