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

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    • Janusz A Z Jankowski
    • John de Caestecker
    • Sharon B Love
    • Gavin Reilly
    • Peter Watson
    • Scott Sanders
    • Yeng Ang
    • 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
    • Rebecca Harrison
    • Hugh Barr
    • Paul Moayyedi

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    BACKGROUND: 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.

    METHODS: 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.

    FINDINGS: 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.

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

    FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

    Documents

    DOI

    Original languageEnglish
    Number of pages9
    Pages (from-to)400-408
    JournalLancet
    Journal publication date04 Aug 2018
    Issue number10145
    Volume392
    Early online date26 Jul 2018
    DOIs
    Publication statusPublished - 04 Aug 2018

    ID: 157602554