Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial

Research output: Contribution to journalArticle

  • External authors:
  • Janusz A Z Jankowski
  • John De Caestecker
  • Sharon B Love
  • Gavin Reilly
  • Peter Watson
  • Scott Sanders
  • Danielle Morris
  • Pradeep Bhandari
  • Stephen Attwood
  • Krish Ragunath
  • Bashir Rameh
  • Grant Fullarton
  • Art Tucker
  • Ian Penman
  • Colin Rodgers
  • James Neale
  • Claire Brooks
  • Adelyn Wise
  • Stephen Jones
  • Nicholas Church
  • Michael Gibbons
  • David Johnston
  • Kishor Vaidya
  • Mark Anderson
  • Sherzad Balata
  • Gareth Davies
  • William Dickey
  • Andrew Goddard
  • Cathryn Edwards
  • Stephen Gore
  • Chris Haigh
  • Timothy Harding
  • Peter Isaacs
  • Lucina Jackson
  • Thomas Lee
  • Peik Loon Lim
  • Christopher Macdonald
  • Philip Mairs
  • James Mcloughlin
  • David Monk
  • Andrew Murdock
  • Iain Murray
  • Sean Preston
  • Stirling Pugh
  • Howard Smart
  • Ashraf Soliman
  • John Todd
  • Graham Turner
  • Joy Worthingon



Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.


The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.


Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01–1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98–1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.


High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.

Bibliographical metadata

Original languageEnglish
Pages (from-to)400-408
JournalThe Lancet
Issue number10145
Early online date26 Jul 2018
Publication statusPublished - 4 Aug 2018