Comparing laparoscopic anti-reflux surgery to esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: A 3-year interim analysis of the LOTUS trial

Lars Lundell ^1*, Stephen Attwood ², Christian Ell ³, Roberto Fiocca ⁴, Jean Paul Galmiche ⁵, Jan Hatlebakk ⁶, Tore Lind ⁷ and Ola Junghard ⁷

¹ Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
² Department of Surgery, North Tyneside General Hospital, Tyne and Wear, United Kingdom
³ Department of Gastroenterology, Dr. Horst Schmidt-Hospital, Wiesbaden, Germany
⁴ Anatomic Pathology Division, University of Genova, Italy
⁵ Nantes University, and CIC INSERM, Nantes, France
⁶ Institute of Medicine, Haukeland University Hospital, University of Bergen, Norway
⁷ Astra Zeneca R & D, Mölndal, Sweden

^* To whom correspondence should be addressed. E-mail: lars.lundell{at}karolinska.se.

Accepted 8 April 2008

Abstract

Background: With the introduction of laparoscopic anti-reflux surgery (LARS) for GORD along with the increasing efficacy of modern medical therapy, a direct comparison is warranted. We report the 3-year interim results of a randomised study comparing both efficacy and safety of LARS and esomeprazole (ESO).

Methods: LOTUS is an open, parallel-group multicentre, randomised, and controlled trial conducted in dedicated centres in eleven European countries. LARS was completed according to a standardised protocol, comprising a total fundoplication and a crural repair. Medical treatment comprised ESO 20 mg od, which could be increased stepwise to 40 mg od and then 20 mg bid in case of incomplete GORD control. The primary outcome variable was time to treatment failure (Kaplan-Meier analysis). Treatment failure was defined on the basis of symptomatic relapse requiring treatment beyond that stated in the protocol.

Results: 554 patients were randomised of whom 288 were allocated to LARS and 266 to ESO. The two study arms were well matched. The proportions of patients who remained in remission after 3 years were similar for the two therapies: 90% of surgical patients compared with 93% medically treated for the ITT population, p=0.25 (90% vs 95% PP). No major unexpected post-operative complications were experienced and ESO was well tolerated. However, post-fundoplication complaints remain a problem after LARS.

Conclusions Over the first 3 years of this long-term study, both laparoscopic total fundoplication and continuous esomeprazole treatment were similarly effective and well-tolerated therapeutic strategies for providing effective control of GORD.