Gastroesophageal RefluxPhase 3LOTUSNCT00251927

Esomeprazole (NEXIUM) vs. Surgery

A Phase 3 study testing esomeprazole and Laparoscopic fundoplication (surgery) in people with Gastroesophageal Reflux, run by AstraZeneca at 59 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Gastroesophageal Reflux
What is being tested?: esomeprazole and Laparoscopic fundoplication (surgery)
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 626 participants
Where: 59 sitesin 12 countries
Study dates: Oct 2001to Apr 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects considered suitable for surgical treatment and long-term management of esomeprazole.
History of chronic reflux esophagitis or symptomatic GERD

Who cannot join

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.

Trial locations and contacts

59 sites in 12 countries.

Country

City, postcode or hospital

59 sites in 12 countries

Germany10 sites

Research Site
Cologne
Research Site
Dresden, 01307
Research Site
Frankfurt
Research Site
Hamburg
Research Site
Heidelberg
Research Site
Herne
Research Site
München
Research Site
Tübingen
Research Site
Wiesbaden
Research Site
Würzburg

Other trials in Germany

Italy10 sites

Research Site
Brescia
Research Site
Florence
Research Site
Modena
Research Site
Monfalcone
Research Site
Padova
Research Site
Perugia
Research Site
Pisa
Research Site
Rozzano
Research Site
San Donato Milanese
Research Site
Torino

Other trials in Italy

Belgium8 sites

Research Site
Brussels
Research Site
Brussels (Anderlecht)
Research Site
Brussels (Woluwé-St-Lambert)
Research Site
Ghent
Research Site
Haine-Saint-Paul
Research Site
Leuven
Research Site
Liège
Research Site
Rimavska Sobota

Other trials in Belgium

Denmark8 sites

Research Site
Århus C
Research Site
Glostrup Municipality
Research Site
Herning
Research Site
Hillerød
Research Site
Hvidovre
Research Site
Kolding
Research Site
Odense C
Research Site
Viborg

Other trials in Denmark

France7 sites

Research Site
Bordeaux
Research Site
Créteil
Research Site
Grenoble
Research Site
Nantes
Research Site
Nice
Research Site
Nîmes
Research Site
Rouen

Other trials in France

Norway6 sites

Research Site
Bergen
Research Site
Bodø
Research Site
Kristiansand
Research Site
Oslo
Research Site
Tromsø
Research Site
Trondheim

Other trials in Norway

Austria3 sites

Research Site
Linz
Research Site
Vienna
Research Site
Zell am See

Other trials in Austria

Finland2 sites

Research Site
Kuopio
Research Site
Tampere

Other trials in Finland

Sweden2 sites

Research Site
Gothenburg
Research Site
Lund

Other trials in Sweden

Iceland1 site

Research Site
Reykjavik

Other trials in Iceland

Netherlands1 site

Research Site
Utrecht

Other trials in Netherlands

United Kingdom1 site

Research Site
Salford

Other trials in United Kingdom

About this study

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.

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.

Conditions: Gastroesophageal Reflux
Being tested: esomeprazole, Laparoscopic fundoplication (surgery)
Keywords: Acid reflux disease, Gastroesophageal Reflux Disease
Medical subject headings: Gastroesophageal Reflux

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

esomeprazoleDrug
Also called Nexium®
40 mg oral tablet administered daily
Laparoscopic fundoplication (surgery)Procedure or surgery
Surgery

Study groups in NCT00251927
Study group	Role	What they receive
1	Active comparator	Surgery Receives: Procedure: Laparoscopic fundoplication (surgery)
2	Experimental	Esomeprazole (NEXIUM) therapy Receives: Drug: esomeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: During 5 years

Secondary outcomes (10)

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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: At 5 year visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2001Apr 2009

First posted11 Nov 2005 (estimated)
Study startOct 2001
Primary completionApr 2009
Study completionApr 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Gastroesophageal RefluxStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 626 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00251927
Sponsor's protocol ID: D9612C00003
Other IDs: SH-NEG-0003
Acronym: LOTUS
Status last verified: Aug 2012
First submitted: 9 Nov 2005
Last updated: 8 Aug 2012
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 26226096
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.
PubMed 25858519
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.
PubMed 25350223
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.
PubMed 22998687
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.
PubMed 21586712

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Gastroesophageal Reflux trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT00251927
Acronym / sponsor ID: LOTUS / D9612C00003
Conditions: Gastroesophageal Reflux
Keywords: Acid reflux disease, Gastroesophageal Reflux Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 626 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Oct 2001
Primary completion: Apr 2009 (actual)
Study completion: Apr 2009 (actual)
First posted: 11 Nov 2005 (estimated)
Results: Posted 8 Aug 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
1	Active comparator	Procedure: Laparoscopic fundoplication (surgery)Surgery
2	Experimental	Drug: esomeprazoleEsomeprazole (NEXIUM) therapy

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Subjects considered suitable for surgical treatment and long-term management of esomeprazole.
History of chronic reflux esophagitis or symptomatic GERD

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
esomeprazoleAlso: Nexium®40 mg oral tablet administered daily	Drug	2
Laparoscopic fundoplication (surgery)Surgery	Procedure or surgery	1

Primary outcome

Number of Participants With Treatment Failure at 5 Years
Time frame: 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.

10 secondary outcomes

Los Angeles (LA) Grade 'Normal' at 5 Year Visit
Time frame: At 5 year visit
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn
Time frame: 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
Time frame: At 5 year visit
Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit
Time frame: At 5 year visit
Los Angeles (LA) Grade 'A' at 5 Year Visit
Time frame: At 5 year visit
Los Angeles (LA) Grade 'B' at 5 Year Visit
Time frame: At 5 year visit
Los Angeles (LA) Grade C at 5 Year Visit
Time frame: At 5 year visit
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn
Time frame: At 5 year visit
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn
Time frame: At 5 year visit
Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn
Time frame: At 5 year visit

Results and safety

Results posted to the registry on 8 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Esomeprazole Surgical Arm	288	180
Esomeprazole Medical Arm	266	192

Primary outcome: Number of Participants With Treatment Failure at 5 Years

Time frame: During 5 years. Number. Unit: participants

Measure	Esomeprazole Surgical Arm n = 288	Esomeprazole Medical Arm n = 266
Value	33	19

10 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Esomeprazole Surgical Arm	103 of 248 (41.5%)	0 of 248 (0%)	Not reported
Esomeprazole Medical Arm	101 of 266 (38%)	0 of 266 (0%)	Not reported
Non-Surgical Arm	3 of 40 (7.5%)	0 of 40 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26226096Hatlebakk 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.
Derived from this study: PubMed 25858519Attwood 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.
Derived from this study: PubMed 25350223Lundell 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.
Derived from this study: PubMed 22998687Fiocca 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.
Derived from this study: PubMed 21586712Galmiche 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.

Related trials for Gastroesophageal Reflux

Recruiting
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RecruitingObservational study
Post-Marketing Surveillance to Evaluate the Safety and Effectiveness of Zastaprazan Citrate
Erosive Gastroesophageal Reflux Disease
Not yet recruitingPhase 4
Effects of Tirzepatide on Esophagogastric Junction Mechanics, Reflux Burden, and Gastric Physiology in Adults With Obesity
Obese Adults
Recruiting
Phrenoesophageal Ligament Reconstruction With Mesh
Hiatus Hernia, Gastreoesophageal Reflux Disease
Recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

AstraZeneca Nexium Medical Sciences Director, MD study director

AstraZeneca

Lars Lundell, MD, PhD principal investigator

Karolinska University Hospital

59 sites in 12 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing esomeprazole and Laparoscopic fundoplication (surgery) in people with Gastroesophageal Reflux, run by AstraZeneca at 59 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in Germany, Italy, Belgium, Denmark, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Failure at 5 Years (time frame: During 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00251927, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2012.