Clinical trial NCT00251927: Esomeprazole (NEXIUM) vs. Surgery
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastroesophageal Reflux
Keywords: Acid reflux disease
Gastroesophageal Reflux Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-11-11
Enrollment: 626
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Treatment Failure at 5 Years
timeFrame: During 5 years
Secondary outcomes:
measure: Los Angeles (LA) Grade 'Normal' at 5 Year Visit
timeFrame: At 5 year visit
measure: Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With no Heartburn
timeFrame: At 5 year visit
measure: Total Score for Microscopic Reflux-related Changes in the Distal Esophagus 2 cm Above the Z-line, at 5 Year Visit
timeFrame: At 5 year visit
measure: Percentage Time With pH<4 During 24-hour pH Metry at 5 Year Visit
timeFrame: At 5 year visit
measure: Los Angeles (LA) Grade 'A' at 5 Year Visit
timeFrame: At 5 year visit
measure: Los Angeles (LA) Grade 'B' at 5 Year Visit
timeFrame: At 5 year visit
measure: Los Angeles (LA) Grade C at 5 Year Visit
timeFrame: At 5 year visit
measure: Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Mild Heartburn
timeFrame: At 5 year visit
measure: Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Moderate Heartburn
timeFrame: At 5 year visit
measure: Investigator-assessed Heartburn Severity at 5 Year Visit, Participants With Severe Heartburn
timeFrame: At 5 year visit
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Zell am See
country: Austria
facility: Research Site
city: Brussels (Anderlecht)
country: Belgium
facility: Research Site
city: Brussels (Woluwé-St-Lambert)
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Haine-Saint-Paul
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Rimavska Sobota
country: Belgium
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Herning
country: Denmark
facility: Research Site
city: Hillerød
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: Kolding
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Viborg
country: Denmark
facility: Research Site
city: Århus C
country: Denmark
facility: Research Site
city: Kuopio
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: GRENOBLE Cedex 09
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: NIMES Cedex 4
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Herne
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Reykjavik
country: Iceland
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Monfalcone
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: San Donato Milanese
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Bergen
country: Norway
facility: Research Site
city: Bodø
country: Norway
facility: Research Site
city: Kristiansand S
country: Norway
facility: Research Site
city: Oslo
country: Norway
facility: Research Site
city: Tromsø
country: Norway
facility: Research Site
city: Trondheim
country: Norway
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Nexium Medical Sciences Director, MD
role: STUDY_DIRECTOR
affiliation: Karolinska University Hospital
name: Lars Lundell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.