LOTUS: Esomeprazole (NEXIUM) vs. Surgery

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00251927
• Collaborator: (none)
• Enrollment: 626
• Locations: 59
• Arms: 2
• Duration (Months): 90
• Patients Per Site: 10.6
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Gastroesophageal Reflux	Drug: esomeprazole; Procedure: Laparoscopic fundoplication (surgery)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 626 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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.
• Study Start Date: Oct 1, 2001
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Surgery	Procedure: Laparoscopic fundoplication (surgery); Surgery
Experimental: 2 Esomeprazole (NEXIUM) therapy	Drug: esomeprazole; 40 mg oral tablet administered daily; Other Names: Nexium®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Failure at 5 Years [During 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

1. Los Angeles (LA) Grade 'Normal' at 5 Year Visit [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

2. Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn [At 5 year visit]

   Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe) Participants with no heartburn

3. Total Score for Microscopic Reflux-related Changes in the Distal Esophagus 2 cm Above the Z-line, at 5 Year Visit [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

4. Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit [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

5. Los Angeles (LA) Grade 'A' at 5 Year Visit [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

6. Los Angeles (LA) Grade 'B' at 5 Year Visit [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

7. Los Angeles (LA) Grade C at 5 Year Visit [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

8. Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn [At 5 year visit]

   Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with mild heartburn

9. Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn [At 5 year visit]

   Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with moderate heartburn

10. Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn [At 5 year visit]

    Presence of heartburn assessed retrospectively by the investigator. Classified by severity (none, mild, moderate, severe). Participants with severe heartburn

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Linz		Austria
2	Research Site	Wien		Austria
3	Research Site	Zell am See		Austria
4	Research Site	Brussels (Anderlecht)		Belgium
5	Research Site	Brussels (Woluwé-St-Lambert)		Belgium
6	Research Site	Brussels		Belgium
7	Research Site	Gent		Belgium
8	Research Site	Haine-Saint-Paul		Belgium
9	Research Site	Leuven		Belgium
10	Research Site	Liège		Belgium
11	Research Site	Rimavska Sobota		Belgium
12	Research Site	Glostrup		Denmark
13	Research Site	Herning		Denmark
14	Research Site	Hillerød		Denmark
15	Research Site	Hvidovre		Denmark
16	Research Site	Kolding		Denmark
17	Research Site	Odense C		Denmark
18	Research Site	Viborg		Denmark
19	Research Site	Århus C		Denmark
20	Research Site	Kuopio		Finland
21	Research Site	Tampere		Finland
22	Research Site	Bordeaux		France
23	Research Site	Creteil		France
24	Research Site	GRENOBLE Cedex 09		France
25	Research Site	Nantes		France
26	Research Site	Nice		France
27	Research Site	NIMES Cedex 4		France
28	Research Site	Rouen		France
29	Research Site	Dresden		Germany	01307
30	Research Site	Frankfurt		Germany
31	Research Site	Hamburg		Germany
32	Research Site	Heidelberg		Germany
33	Research Site	Herne		Germany
34	Research Site	Köln		Germany
35	Research Site	München		Germany
36	Research Site	Tübingen		Germany
37	Research Site	Wiesbaden		Germany
38	Research Site	Würzburg		Germany
39	Research Site	Reykjavik		Iceland
40	Research Site	Brescia		Italy
41	Research Site	Firenze		Italy
42	Research Site	Modena		Italy
43	Research Site	Monfalcone		Italy
44	Research Site	Padova		Italy
45	Research Site	Perugia		Italy
46	Research Site	Pisa		Italy
47	Research Site	Rozzano		Italy
48	Research Site	San Donato Milanese		Italy
49	Research Site	Torino		Italy
50	Research Site	Utrecht		Netherlands
51	Research Site	Bergen		Norway
52	Research Site	Bodø		Norway
53	Research Site	Kristiansand S		Norway
54	Research Site	Oslo		Norway
55	Research Site	Tromsø		Norway
56	Research Site	Trondheim		Norway
57	Research Site	Göteborg		Sweden
58	Research Site	Lund		Sweden
59	Research Site	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00251927
• Other Study ID Numbers: D9612C00003; SH-NEG-0003
• First Posted: Nov 11, 2005
• Last Update Posted: Aug 8, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by AstraZeneca: Acid reflux disease; Gastroesophageal Reflux Disease
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic; Esomeprazole

Study Results

Participant Flow

Recruitment Details	The first patient was enrolled on 16 October 2001. Last patient completed the last visit on 07 April 2009.
Pre-assignment Detail	The study started with a 12-week run-in period. Patients had either been treated or untreated with a proton pump inhibitor (PPI) prior to entering this phase of the study.

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Period Title: Overall Study
STARTED	288	266
COMPLETED	180	192
NOT COMPLETED	108	74

Baseline Characteristics

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm	Total
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)	Total of all reporting groups
Overall Participants	288	266	554
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.8 (10.9)	45.3 (11.5)	45.05 (11.2)
Sex: Female, Male (Count of Participants)
Female	89 30.9%	67 25.2%	156 28.2%
Male	199 69.1%	199 74.8%	398 71.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	33 11.5%	19 7.1%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	144 50%	158 59.4%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	163 56.6%	161 60.5%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	153	177
Mean (Standard Error) [units on a scale]	0.23 (0.10)	0.25 (0.03)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	124	162
Mean (Standard Deviation) [percentage of time recorded]	2.9 (7.0)	4.7 (7.0)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	12 4.2%	16 6%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	5 1.7%	7 2.6%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	1 0.3%	2 0.8%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	11 3.8%	25 9.4%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	3 1%	3 1.1%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Esomeprazole Surgical Arm	Esomeprazole Medical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)
Measure Participants	288	266
Number [participants]	0 0%	2 0.8%

Adverse Events

Arm/Group Title	Esomeprazole Surgical Arm		Esomeprazole Medical Arm		Non-Surgical Arm
Arm/Group Description	Esomeprazole 40 mg once daily during a 12-week run-in period, followed by laparoscopic anti-reflux fundoplication anti-reflux surgery.		Esomeprazole 40 mg once daily during a 12-week run-in period, followed by esomeprazole treatment (start dose 20 mg once daily, if needed adjusted to 40 mg once daily)		This group of patients was randomized to receive surgery but were on operated on and were followed for safety purposes
All Cause Mortality
	Esomeprazole Surgical Arm		Esomeprazole Medical Arm		Non-Surgical Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Esomeprazole Surgical Arm		Esomeprazole Medical Arm		Non-Surgical Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/248 (41.5%)		101/266 (38%)		3/40 (7.5%)
Blood and lymphatic system disorders
Microcytic Anaemia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Cardiac disorders
Acute Myocardial Infarction	0/248 (0%)		2/266 (0.8%)		0/40 (0%)
Angina Pectoris	1/248 (0.4%)		3/266 (1.1%)		0/40 (0%)
Arrhythmia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Arteriosclerosis Coronary Artery	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Atrial Fibrillation	0/248 (0%)		1/266 (0.4%)		1/40 (2.5%)
Cardiac Failure	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Coronary Artery Disease	2/248 (0.8%)		0/266 (0%)		0/40 (0%)
Coronary Artery Stenosis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Myocardial Infarction	2/248 (0.8%)		3/266 (1.1%)		0/40 (0%)
Myocardial Ischaemia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Palpitations	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Pericarditis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Sinus Tachycardia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Ear and labyrinth disorders
Conductive Deafness	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Endocrine disorders
Hyperthyroidism	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Eye disorders
Cataract	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Corneal Oedema	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Glaucoma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Keratitis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Retinal Vein Occlusion	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Gastrointestinal disorders
Abdominal Hernia	2/248 (0.8%)		1/266 (0.4%)		0/40 (0%)
Abdominal Pain	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Acute Abdomen	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Barrett's Oesophagus	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Colitis Ulcerative	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Colonic Pseudo-Obstruction	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Constipation	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Diverticulitis Intestinal Haemorrhagic	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Dysphagia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Flatulence	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Gastric Perforation	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Gastric Ulcer Perforation	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Gastritis Haemorrhagic	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Gastrointestinal Motility Disorder	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Gastrooesophageal Reflux Disease	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Haemorrhoids	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Ileus	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Ileus Paralytic	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Impaired Gastric Emptying	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Large Intestine Perforation	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Lumbar Hernia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Mallory-Weiss Syndrome	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Subileus	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Chest Discomfort	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
General disorders
Dysplasia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Multi-Organ Failure	0/248 (0%)		0/266 (0%)		0/40 (0%)
Non-Cardiac Chest Pain	3/248 (1.2%)		5/266 (1.9%)		0/40 (0%)
Oedema Peripheral	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Pyrexia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Hepatobiliary disorders
Bile Duct Stenosis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Bile Duct Stone	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Cholecystitis	1/248 (0.4%)		2/266 (0.8%)		1/40 (2.5%)
Cholecystitis Acute	0/248 (0%)		0/266 (0%)		0/40 (0%)
Cholelithiasis	3/248 (1.2%)		0/266 (0%)		0/40 (0%)
Infections and infestations
Abscess Jaw	0/248 (0%)		0/266 (0%)		1/40 (2.5%)
Appendicitis	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Diverticulitis	0/248 (0%)		2/266 (0.8%)		0/40 (0%)
Erysipelas	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Gastroenteritis	1/248 (0.4%)		3/266 (1.1%)		0/40 (0%)
Pneumonia	0/248 (0%)		2/266 (0.8%)		0/40 (0%)
Pneumonia Primary Atypical	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Sepsis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Tubo-Ovarian Abscess	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Urinary Tract Infection	2/248 (0.8%)		0/266 (0%)		0/40 (0%)
Injury, poisoning and procedural complications
Complication Of Device Insertion	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Fall	0/248 (0%)		0/266 (0%)		0/40 (0%)
Femur Fracture	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Gas Poisoning	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Incisional Hernia	3/248 (1.2%)		0/266 (0%)		0/40 (0%)
Meniscus Lesion	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Operative Haemorrhage	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Overdose	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Patella Fracture	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Pelvic Fracture	0/248 (0%)		0/266 (0%)		0/40 (0%)
Post Procedural Complication	4/248 (1.6%)		0/266 (0%)		0/40 (0%)
Procedural Complication	2/248 (0.8%)		0/266 (0%)		0/40 (0%)
Procedural Pain	3/248 (1.2%)		0/266 (0%)		0/40 (0%)
Radius Fracture	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Skull Fracture	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Tendon Rupture	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Traumatic Brain Injury	0/248 (0%)		0/266 (0%)		0/40 (0%)
Urinary Bladder Rupture	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Vascular Pseudoaneurysm	0/248 (0%)		2/266 (0.8%)		0/40 (0%)
Metabolism and nutrition disorders
Diabetes Mellitus	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Hyponatraemia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Bursitis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Chondropathy	1/248 (0.4%)		2/266 (0.8%)		0/40 (0%)
Foot Deformity	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Intervertebral Disc Protrusion	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Musculoskeletal Chest Pain	1/248 (0.4%)		4/266 (1.5%)		0/40 (0%)
Musculoskeletal Pain	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Osteoarthritis	4/248 (1.6%)		2/266 (0.8%)		0/40 (0%)
Rotator Cuff Syndrome	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Spondylolisthesis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Tendonitis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Pancreas	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Benign Neoplasm Of Thyroid Gland	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Benign Peritoneal Neoplasm	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Breast Cancer	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Carcinoid Tumour Pulmonary	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Chronic Lymphocytic Leukaemia	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Lung Neoplasm Malignant	0/248 (0%)		0/266 (0%)		0/40 (0%)
Lymphoma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Malignant Neoplasm Of Spermatic Cord	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Multiple Myeloma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Ovarian Cancer	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Pancreatic Carcinoma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Prostate Cancer	1/248 (0.4%)		2/266 (0.8%)		0/40 (0%)
Seminoma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Tongue Neoplasm	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Uterine Leiomyoma	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Nervous system disorders
Carotid Artery Stenosis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Cerebral Infarction	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Cerebrovascular Accident	2/248 (0.8%)		1/266 (0.4%)		0/40 (0%)
Headache	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Polyneuropathy	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Sciatica	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Subarachnoid Haemorrhage	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Transient Ischaemic Attack	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Psychiatric disorders
Anxiety Disorder	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Depression	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Suicide Attempt	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Renal and urinary disorders
Calculus Ureteric	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Nephrolithiasis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	1/248 (0.4%)		2/266 (0.8%)		0/40 (0%)
Epididymitis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Menorrhagia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Metrorrhagia	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Ovarian Torsion	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Uterine Polyp	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Vaginal Prolapse	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Epistaxis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Pleurisy	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Pneumothorax	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Suffocation Feeling	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Vocal Cord Cyst	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Skin and subcutaneous tissue disorders
Skin Fissures	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Vascular disorders
Aortic Aneurysm	0/248 (0%)		2/266 (0.8%)		0/40 (0%)
Arterial Thrombosis Limb	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Arteriosclerosis	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Embolism	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Hypertension	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Hypertensive Crisis	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Necrosis Ischaemic	0/248 (0%)		1/266 (0.4%)		0/40 (0%)
Peripheral Arterial Occlusive Disease	1/248 (0.4%)		1/266 (0.4%)		0/40 (0%)
Varicose Vein	1/248 (0.4%)		0/266 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Esomeprazole Surgical Arm		Esomeprazole Medical Arm		Non-Surgical Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/248 (0%)		0/266 (0%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.