Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX)BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f1908 (Published 18 April 2013) Cite this as: BMJ 2013;346:f1908
- A M Grant, professor of health services research1,
- S C Cotton, trial coordinator1,
- C Boachie, statistician1,
- C R Ramsay, professor of health services research1,
- Z H Krukowski, professor of clinical surgery2,
- R C Heading, honorary professor3,
- M K Campbell, director1
- the REFLUX Trial Group
- 1Health Services Research Unit, University of Aberdeen, Aberdeen AB25 2ZD, UK
- 2Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK
- 3School of Medicine and Health, Wolfson Research Institute, Durham University, Queen’s Campus, Stockton-on-Tees, TS17 6BH, UK
- Correspondence to: A M Grant
- Accepted 25 November 2012
Objectives To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD).
Design Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups).
Setting Initial recruitment in 21 UK hospitals.
Participants Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months.
Intervention The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care.
Main outcome measures Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications.
Results By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations—most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups.
Conclusions After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery.
Trial registration Current Controlled Trials ISRCTN15517081.
We thank Janice Cruden and Pauline Garden for their secretarial support and data management; Samantha Wileman and Julie Bruce for help with the overview of trials; Samantha Wileman, Maureen G C Gillan, Marie Cameron, Christiane Pflanz-Sinclair, and Lynne Swan for their assistance in nurse coordination and patient recruitment and follow-up; Sharon McCann for assistance in the piloting of the practical arrangements of this trial; and Allan Walker, Daniel Barnett, and Gladys McPherson for database and programming support.
Contributors: AMG was the principal grant holder, helped develop the trial protocol and prepare the paper, and was responsible for the overall conduct and reporting of the study. SCC was responsible for the day to day management of the trial, monitored data collection, and helped prepare the paper. CB conducted the statistical analysis. CRR helped with the grant application and trial design and conducted the statistical analysis. ZHK advised on clinical aspects of the trial and commented on the paper. RCH advised on clinical aspects of the trial design and the conduct of the trial and commented on the paper. MKC helped develop the trial design and contributed to all aspects of the conduct of the trial. AMG is the guarantor for this paper.
Members of the REFLUX Trial Group primarily responsible for the economic evaluation of the trial (reported separately) were Rita Faria, Laura Bojke, David Epstein, Belen Corbacho, and Mark Sculpher.
Members of the REFLUX Trial Group responsible for recruitment in the clinical centres were: A Mowat, Z Krukowski, E El-Omar, P Phull, T Sinclair, Aberdeen Royal Infirmary; B Clements, J Collins, A Kennedy, H Lawther, Royal Victoria Hospital, Belfast; D Bennett, N Davies, S Toop, P Winwood, Royal Bournemouth Hospital; D Alderson, P Barham, K Green, R Mittal, Bristol Royal Infirmary; M Asante, S El Hasani, Princess Royal University Hospital, Bromley; A De Beaux, R Heading, L Meekison, S Paterson-Brown, H Barkell, Royal Infirmary of Edinburgh; G Ferns, M Bailey, N Karanjia, TA Rockall, L Skelly, Royal Surrey County Hospital, Guildford; M Dakkak, J King, C Royston, P Sedman, Hull Royal Infirmary; K Gordon, LF Potts, C Smith, PL Zentler-Munro, A Munro, Raigmore Hospital, Inverness; S Dexter, P Maoyeddi, General Infirmary at Leeds; DM Lloyd, Leicester Royal Infirmary; V Loh, M Thursz, A Darzi, St Mary’s Hospital, London; A Ahmed, R Greaves, A Sawyerr, J Wellwood, T Taylor, Whipps Cross Hospital, London; S Hosking, S Lowrey, J Snook, Poole Hospital; P Goggin, T Johns, A Quine, S Somers, S Toh, Queen Alexandra Hospital, Portsmouth; J Bancewicz, M Greenhalgh, W Rees, Hope Hospital, Salford; CVN Cheruvu, M Deakin, S Evans, J Green, F Leslie, North Staffordshire Hospital, Stoke-on-Trent; JN Baxter, P Duane, MM Rahman, M Thomas, J Williams, Morriston Hospital, Swansea; D Maxton, A Sigurdsson, MSH Smith, G Townson, Princess Royal Hospital, Telford; S Gore, RH Kennedy, ZH Khan, J Knight, Yeovil District Hospital; D Alexander, G Miller, D Parker, A Turnbull, J Turvill, York District Hospital.
Funding: This project was funded by the NIHR Health Technology Assessment Programme (Project No 97/10/03) and will be published in full in Health Technology Assessment. See the HTA Programme website for further information. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate.
This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA Programme, or the Department of Health.
The sponsor had no direct role in the study design, analysis or reporting of the study. The researchers are independent of the funder.
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support for the submitted work; RCH has received money from Reckitt Benckiser as chairman of its Medical Advisory Board and for consultancy and lectures, he has also received money for lectures from Nycomed (Takeda) and holds stock in Procter & Gamble, Reckitt Benckiser, and Novartis; AMG received partial salary support from the NIHR as director of the NIHR Programme Grants for Applied Research programme; no other relationships or activities that could appear to have influenced the submitted work have been declared.
Ethical approval: The study was approved by the Scotland A Multicentre Research Ethics Committee (MREC/00/0/30).
Data sharing: An anonymised study dataset is available on request subject to resource implications and proposed use.
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