Esomeprazole (NEXIUM) vs. Surgery (LOTUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00251927
First received: November 9, 2005
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux
Drug: esomeprazole
Procedure: Laparoscopic fundoplication (surgery)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Participants With Treatment Failure at 5 Years [ Time Frame: During 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Los Angeles (LA) Grade 'Normal' at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]

    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


  • Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe) Participants with no heartburn

  • Total Score for Microscopic Reflux-related Changes in the Distal Esophagus 2 cm Above the Z-line, at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    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

  • Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    Intra-gastric acid exposures assessed by 24-h pH-metry. Only participants with pH-emtry performed at 5 year visit included

  • Los Angeles (LA) Grade 'A' at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]

    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


  • Los Angeles (LA) Grade 'B' at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]

    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


  • Los Angeles (LA) Grade C at 5 Year Visit [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]

    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


  • Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with mild heartburn

  • Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with moderate heartburn

  • Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn [ Time Frame: At 5 year visit ] [ Designated as safety issue: No ]
    Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with severe heartburn


Enrollment: 626
Study Start Date: October 2001
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Surgery
Procedure: Laparoscopic fundoplication (surgery)
Surgery
Experimental: 2
Esomeprazole (NEXIUM) therapy
Drug: esomeprazole
40 mg oral tablet administered daily
Other Name: Nexium®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00251927

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Locations
Austria
Research Site
Linz, Austria
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Wien, Austria
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Zell am See, Austria
Belgium
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Brussels, Belgium
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Brussels (Anderlecht), Belgium
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Brussels (Woluwé-St-Lambert), Belgium
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Gent, Belgium
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Haine-Saint-Paul, Belgium
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Leuven, Belgium
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Liège, Belgium
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Rimavska Sobota, Belgium
Denmark
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Glostrup, Denmark
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Herning, Denmark
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Hillerød, Denmark
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Hvidovre, Denmark
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Kolding, Denmark
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Odense C, Denmark
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Viborg, Denmark
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Århus C, Denmark
Finland
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Kuopio, Finland
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Tampere, Finland
France
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Bordeaux, France
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Creteil, France
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GRENOBLE Cedex 09, France
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Nantes, France
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Nice, France
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NIMES Cedex 4, France
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Rouen, France
Germany
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Dresden, Germany, 01307
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Frankfurt, Germany
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Hamburg, Germany
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Heidelberg, Germany
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Herne, Germany
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Köln, Germany
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München, Germany
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Tübingen, Germany
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Wiesbaden, Germany
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Würzburg, Germany
Iceland
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Reykjavik, Iceland
Italy
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Brescia, Italy
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Firenze, Italy
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Modena, Italy
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Monfalcone, Italy
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Padova, Italy
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Perugia, Italy
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Pisa, Italy
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Rozzano, Italy
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San Donato Milanese, Italy
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Torino, Italy
Netherlands
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Utrecht, Netherlands
Norway
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Bergen, Norway
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Bodø, Norway
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Kristiansand S, Norway
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Oslo, Norway
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Tromsø, Norway
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Trondheim, Norway
Sweden
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Göteborg, Sweden
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Lund, Sweden
United Kingdom
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Salford, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: AstraZeneca Nexium Medical Sciences Director, MD AstraZeneca
Principal Investigator: Lars Lundell, MD, PhD Karolinska University Hospital
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00251927     History of Changes
Other Study ID Numbers: D9612C00003, SH-NEG-0003
Study First Received: November 9, 2005
Results First Received: July 8, 2010
Last Updated: August 7, 2012
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by AstraZeneca:
Acid reflux disease
Gastroesophageal Reflux Disease

Additional relevant MeSH terms:
Gastroesophageal Reflux
Deglutition Disorders
Digestive System Diseases
Esophageal Diseases
Esophageal Motility Disorders
Gastrointestinal Diseases
Esomeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014