Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
Elsevier
2018
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| _version_ | 1797061776478568448 |
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| author | Jankowski, J de Caestecker, J Love, S 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 Church, N |
| author_facet | Jankowski, J de Caestecker, J Love, S 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 Church, N |
| author_sort | Jankowski, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:36:07Z |
| format | Journal article |
| id | oxford-uuid:32af0433-bbef-46c8-91c8-99df5ccecfea |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:36:07Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:32af0433-bbef-46c8-91c8-99df5ccecfea2022-03-26T13:15:48ZEsomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:32af0433-bbef-46c8-91c8-99df5ccecfeaSymplectic Elements at OxfordElsevier2018Jankowski, Jde Caestecker, JLove, SReilly, GWatson, PSanders, SAng, YMorris, DBhandari, PAttwood, SRagunath, KRameh, BFullarton, GTucker, APenman, IRodgers, CNeale, JBrooks, CWise, AJones, SChurch, NBackground: 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. |
| spellingShingle | Jankowski, J de Caestecker, J Love, S 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 Church, N Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title_full | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title_fullStr | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title_full_unstemmed | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title_short | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial |
| title_sort | esomeprazole and aspirin in barrett s oesophagus aspect a randomised factorial trial |
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