Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT)
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: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Elsevier
2018
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/52852/ |
| _version_ | 1848798824119664640 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Jankowski, Janusz A.Z. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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 | 2025-11-14T20:25:54Z |
| format | Article |
| id | nottingham-52852 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:25:54Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-528522020-05-04T19:42:34Z https://eprints.nottingham.ac.uk/52852/ Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) 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 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. Elsevier 2018-06-27 Article PeerReviewed 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 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) Aspirin Barrett’s oesophagus cancer chemoprevention randomized clinical trial proton pump inhibitors. |
| spellingShingle | Aspirin Barrett’s oesophagus cancer chemoprevention randomized clinical trial proton pump inhibitors. 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 Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title | Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title_full | Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title_fullStr | Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title_full_unstemmed | Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title_short | Randomized factorial trial of esomeprazole and aspirin in Barrett’s oesophagus: the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) |
| title_sort | randomized factorial trial of esomeprazole and aspirin in barrett’s oesophagus: the aspirin and esomeprazole chemoprevention in barrett’s metaplasia trial (aspect) |
| topic | Aspirin Barrett’s oesophagus cancer chemoprevention randomized clinical trial proton pump inhibitors. |
| url | https://eprints.nottingham.ac.uk/52852/ |