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

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

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.

Citation

Jankowski, J. A., de Caestecker, J., Love, S. B., Reilly, G., Watson, P., Sanders, S., Ang, Y., Morris, D., Bhandari, P., Attwood, S., Ragunath, K., Rameh, B., Fullarton, G., Tucker, A., Penman, I., Rodgers, C., Neale, J., Brooks, C., Wise, A., Jones, S., …Moayyedi, P. (2018). Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial. Lancet, 392(10145), 400-408. https://doi.org/10.1016/S0140-6736%2818%2931388-6

• Journal Article Type: Article
• Acceptance Date: Jun 27, 2018
• Online Publication Date: Jul 26, 2018
• Publication Date: Aug 4, 2018
• Deposit Date: Jul 11, 2018
• Publicly Available Date: Jul 26, 2018
• Journal: Lancet Gastroenterology and Hepatology
• Print ISSN: 0140-6736
• Electronic ISSN: 1474-547X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 392
• Issue: 10145
• Pages: 400-408
• DOI: https://doi.org/10.1016/S0140-6736%2818%2931388-6
• Keywords: Aspirin, Barrett’s oesophagus, cancer, chemoprevention, randomized clinical trial, proton pump inhibitors.
• Public URL: https://nottingham-repository.worktribe.com/output/942038
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0140673618313886?via%3Dihub
• Contract Date: Jul 11, 2018