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Jankowski, Janusz A.Z. and de Caestecker, John and Love, Sharon B. and Reilly, Gavin and Watson, Peter and Sanders, Scott and Ang, Yeng and Morris, Danielle and Bhandari, Pradeep and Attwood, Stephen and Ragunath, Krish and Rameh, Bashir and Fullarton, Grant and Tucker, Art and Penman, Ian and Rodgers, Colin and Neale, James and Brooks, Claire and Wise, Adelyn and Jones, Stephen and Church, Nicholas and Gibbons, Michael and Johnston, David and Vaidya, Kishor and Anderson, Mark and Balata, Sherzad and Davies, Gareth and Dickey, William and Goddard, Andrew and Edwards, Cathryn and Gore, Stephen and Haigh, Chris and Harding, Timothy and Isaacs, Peter and Jackson, Lucina and Lee, Thomas and Lim, Peik Loon and Macdonald, Christopher and Mairs, Philip and McLoughlin, James and Monk, David and Murdock, Andrew and Murray, Iain and Preston, Sean and Pugh, Stirling and Smart, Howard and Soliman, Ashraf and Todd, John and Turner, Graham and Worthington, Joy and Harrison, Rebecca and Barr, Hugh and Moayyedi, Paul (2018) Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT). Lancet Gastroenterology and Hepatology . ISSN 2468-1253 (In Press)

Abstract

Background: Oesophageal adenocarcinoma (OA) is the sixth commonest cause of cancer death worldwide and Barrett’s oesophagus (BO) is the most significant risk factor. We evaluated the efficacy of high-dose esomeprazole proton pump inhibitor acid suppression (PPI) and aspirin in improving outcome for BO patients in the largest such randomized controlled trial.

Methods: Patients with ≥1cm BO in UK and Canadian hospitals were randomized 1:1:1:1 using a computer-generated schedule held in a central trials unit in a 2X2 factorial design to high-dose (40mg twice-daily) or low-dose (20mg once-daily) PPI, alone or with aspirin (UK: 300mg/day, Canada: 325mg/day), unblinded (reporting pathologists blinded). The primary composite endpoint was time to all-cause mortality, OA, or high-grade dysplasia, analysed using accelerated failure time modelling adjusted for minimization factors (age, BO length, intestinal metaplasia).

Findings: Recruited patients (N=2557) were followed for 8·9 years (median; interquartile range 8·2–9·8), collecting 20,095 follow-up years and 99·9% of planned data. There were 313 primary events. High-dose PPI was superior to low-dose PPI (p=0·037, N=1265 (low dose), N=1270 (high dose), time ratio (TR)=1·27, 95%CI=1·01–1·58). Aspirin was not significantly better than no aspirin (p=0·068, N=1142 (no aspirin), N = 1138 (aspirin), TR=1·24, 95%CI=0·98–1·57). If patients using NSAIDs were censored at time of first use,aspirin was significantly better than no Aspirin (p=0·043, N=2,236, TR=1·29 95%CI=1·01– 1·66). Combining high-dose PPI with aspirin had the strongest effect compared with low dose PPI without aspirin (p=0·0068, TR=1·59, 95%CI=1·14–2·23). NNT for PPI and aspirin benefit is 34 and 43, respectively. Only 1·0% (28) of participants reported study-treatment related serious adverse events.

Interpretation: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improve outcome in BO patients.

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