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Esomeprazole (NEXIUM) vs. Surgery (LOTUS)

Primary Purpose

Gastroesophageal Reflux

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
esomeprazole
Laparoscopic fundoplication (surgery)
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastroesophageal Reflux focused on measuring Acid reflux disease, Gastroesophageal Reflux Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

Surgery

Esomeprazole (NEXIUM) therapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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
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
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
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
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
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
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

Full Information

First Posted
November 9, 2005
Last Updated
August 7, 2012
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00251927
Brief Title
Esomeprazole (NEXIUM) vs. Surgery
Acronym
LOTUS
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroesophageal Reflux
Keywords
Acid reflux disease, Gastroesophageal Reflux Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
626 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Surgery
Arm Title
2
Arm Type
Experimental
Arm Description
Esomeprazole (NEXIUM) therapy
Intervention Type
Drug
Intervention Name(s)
esomeprazole
Other Intervention Name(s)
Nexium®
Intervention Description
40 mg oral tablet administered daily
Intervention Type
Procedure
Intervention Name(s)
Laparoscopic fundoplication (surgery)
Intervention Description
Surgery
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Failure at 5 Years
Description
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.
Time Frame
During 5 years
Secondary Outcome Measure Information:
Title
Los Angeles (LA) Grade 'Normal' at 5 Year Visit
Description
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
Time Frame
At 5 year visit
Title
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn
Description
Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe) Participants with no heartburn
Time Frame
At 5 year visit
Title
Total Score for Microscopic Reflux-related Changes in the Distal Esophagus 2 cm Above the Z-line, at 5 Year Visit
Description
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
Time Frame
At 5 year visit
Title
Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit
Description
Intra-gastric acid exposures assessed by 24-h pH-metry. Only participants with pH-emtry performed at 5 year visit included
Time Frame
At 5 year visit
Title
Los Angeles (LA) Grade 'A' at 5 Year Visit
Description
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
Time Frame
At 5 year visit
Title
Los Angeles (LA) Grade 'B' at 5 Year Visit
Description
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
Time Frame
At 5 year visit
Title
Los Angeles (LA) Grade C at 5 Year Visit
Description
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
Time Frame
At 5 year visit
Title
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn
Description
Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with mild heartburn
Time Frame
At 5 year visit
Title
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn
Description
Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with moderate heartburn
Time Frame
At 5 year visit
Title
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn
Description
Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with severe heartburn
Time Frame
At 5 year visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AstraZeneca Nexium Medical Sciences Director, MD
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Lars Lundell, MD, PhD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Linz
Country
Austria
Facility Name
Research Site
City
Wien
Country
Austria
Facility Name
Research Site
City
Zell am See
Country
Austria
Facility Name
Research Site
City
Brussels (Anderlecht)
Country
Belgium
Facility Name
Research Site
City
Brussels (Woluwé-St-Lambert)
Country
Belgium
Facility Name
Research Site
City
Brussels
Country
Belgium
Facility Name
Research Site
City
Gent
Country
Belgium
Facility Name
Research Site
City
Haine-Saint-Paul
Country
Belgium
Facility Name
Research Site
City
Leuven
Country
Belgium
Facility Name
Research Site
City
Liège
Country
Belgium
Facility Name
Research Site
City
Rimavska Sobota
Country
Belgium
Facility Name
Research Site
City
Glostrup
Country
Denmark
Facility Name
Research Site
City
Herning
Country
Denmark
Facility Name
Research Site
City
Hillerød
Country
Denmark
Facility Name
Research Site
City
Hvidovre
Country
Denmark
Facility Name
Research Site
City
Kolding
Country
Denmark
Facility Name
Research Site
City
Odense C
Country
Denmark
Facility Name
Research Site
City
Viborg
Country
Denmark
Facility Name
Research Site
City
Århus C
Country
Denmark
Facility Name
Research Site
City
Kuopio
Country
Finland
Facility Name
Research Site
City
Tampere
Country
Finland
Facility Name
Research Site
City
Bordeaux
Country
France
Facility Name
Research Site
City
Creteil
Country
France
Facility Name
Research Site
City
GRENOBLE Cedex 09
Country
France
Facility Name
Research Site
City
Nantes
Country
France
Facility Name
Research Site
City
Nice
Country
France
Facility Name
Research Site
City
NIMES Cedex 4
Country
France
Facility Name
Research Site
City
Rouen
Country
France
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Research Site
City
Frankfurt
Country
Germany
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Heidelberg
Country
Germany
Facility Name
Research Site
City
Herne
Country
Germany
Facility Name
Research Site
City
Köln
Country
Germany
Facility Name
Research Site
City
München
Country
Germany
Facility Name
Research Site
City
Tübingen
Country
Germany
Facility Name
Research Site
City
Wiesbaden
Country
Germany
Facility Name
Research Site
City
Würzburg
Country
Germany
Facility Name
Research Site
City
Reykjavik
Country
Iceland
Facility Name
Research Site
City
Brescia
Country
Italy
Facility Name
Research Site
City
Firenze
Country
Italy
Facility Name
Research Site
City
Modena
Country
Italy
Facility Name
Research Site
City
Monfalcone
Country
Italy
Facility Name
Research Site
City
Padova
Country
Italy
Facility Name
Research Site
City
Perugia
Country
Italy
Facility Name
Research Site
City
Pisa
Country
Italy
Facility Name
Research Site
City
Rozzano
Country
Italy
Facility Name
Research Site
City
San Donato Milanese
Country
Italy
Facility Name
Research Site
City
Torino
Country
Italy
Facility Name
Research Site
City
Utrecht
Country
Netherlands
Facility Name
Research Site
City
Bergen
Country
Norway
Facility Name
Research Site
City
Bodø
Country
Norway
Facility Name
Research Site
City
Kristiansand S
Country
Norway
Facility Name
Research Site
City
Oslo
Country
Norway
Facility Name
Research Site
City
Tromsø
Country
Norway
Facility Name
Research Site
City
Trondheim
Country
Norway
Facility Name
Research Site
City
Göteborg
Country
Sweden
Facility Name
Research Site
City
Lund
Country
Sweden
Facility Name
Research Site
City
Salford
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26226096
Citation
Hatlebakk JG, Zerbib F, Bruley des Varannes S, Attwood SE, Ell C, Fiocca R, Galmiche JP, Eklund S, Langstrom G, Lind T, Lundell LR; LOTUS Study Group. Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy. Clin Gastroenterol Hepatol. 2016 May;14(5):678-85.e3. doi: 10.1016/j.cgh.2015.07.025. Epub 2015 Jul 27.
Results Reference
derived
PubMed Identifier
25858519
Citation
Attwood SE, Ell C, Galmiche JP, Fiocca R, Hatlebakk JG, Hasselgren B, Langstrom G, Jahreskog M, Eklund S, Lind T, Lundell L. Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther. 2015 Jun;41(11):1162-74. doi: 10.1111/apt.13194. Epub 2015 Apr 10.
Results Reference
derived
PubMed Identifier
25350223
Citation
Lundell L, Hatlebakk J, Galmiche JP, Attwood SE, Ell C, Fiocca R, Persson T, Nagy P, Eklund S, Lind T. Long-term effect on symptoms and quality of life of maintenance therapy with esomeprazole 20 mg daily: a post hoc analysis of the LOTUS trial. Curr Med Res Opin. 2015 Jan;31(1):65-73. doi: 10.1185/03007995.2014.980500. Epub 2014 Oct 31.
Results Reference
derived
PubMed Identifier
22998687
Citation
Fiocca R, Mastracci L, Attwood SE, Ell C, Galmiche JP, Hatlebakk J, Barthel A, Langstrom G, Lind T, Lundell L; LOTUS trial collaborators. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5-year follow-up in the LOTUS trial. Aliment Pharmacol Ther. 2012 Nov;36(10):959-71. doi: 10.1111/apt.12052. Epub 2012 Sep 23.
Results Reference
derived
PubMed Identifier
21586712
Citation
Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, Langstrom G, Lind T, Lundell L; LOTUS Trial Collaborators. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011 May 18;305(19):1969-77. doi: 10.1001/jama.2011.626.
Results Reference
derived

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Esomeprazole (NEXIUM) vs. Surgery

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