Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial
Hull MA, Sprange K, Hepburn T, Tan W, Shafayat A, Rees CJ, Clifford G, Logan RF, Loadman PM, Williams EA, Whitham D, Montgomery AA, seAFOod Collaborative Group
Lancet (London, England) · 124 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- National Institute for Health and Care Research
- University or hospital
- University of Leeds
- Government
- Medical Research Council
- Government
- Efficacy and Mechanism Evaluation Programme
- Government
- National Institute for Health Research (NIHR)
- Authors
- At least one author declares a financial tie to industry
- Grants
- Efficacy and Mechanism Evaluation Programme (09/100/25); Medical Research Council (MC_G1002465); National Institute for Health and Care Research (09/100/25)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-11-19 · Lancet · vol. 392 · issue 10164 · pp. 2583–2594
- Publisher
- Elsevier BV
- Cited
- 149 citations · more than 97% of similar papers · 5.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 29 works
- Access
- Open access (hybrid journal) · CC-BY
- Research areas
- Colorectal Cancer Screening and Detection · Inflammatory mediators and NSAID effects · Fatty Acid Research and Health
- Keywords
- Eicosapentaenoic acid, Clinical trial, Colorectal adenoma, Dietary supplement, Randomized controlled trial, MEDLINE
- MeSH
- humans, adenoma, colorectal neoplasms, aspirin, eicosapentaenoic acid, anticarcinogenic agents, colonoscopy, drug therapy, combination, double-blind method, aged, middle aged, female, male
12 authors
From GB
- Mark A HullSt James's University Hospital
- Kirsty SprangeUniversity of Nottingham; Queen's Medical Centre
- Trish HepburnUniversity of Nottingham; Queen's Medical Centre
- Wei TanUniversity of Nottingham; Queen's Medical Centre
- Aisha ShafayatUniversity of Nottingham; Queen's Medical Centre
- Colin J ReesNewcastle University
Abstract
Background
The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy.
Methods
In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55-73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847.
Findings
Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group).
Interpretation
Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.
Funding
Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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