{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:12:19Z","timestamp":1782846739673,"version":"3.54.5"},"reference-count":102,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["09\/55\/52"],"award-info":[{"award-number":["09\/55\/52"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title>\n<jats:p>Peptic ulcers in patients on aspirin are associated with <jats:italic>Helicobacter pylori<\/jats:italic> infection. We investigated whether <jats:italic>H. pylori<\/jats:italic> eradication would protect against aspirin-associated ulcer bleeding.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-2\"><jats:title>Methods<\/jats:title>\n<jats:p>The <jats:italic>Helicobacter<\/jats:italic> Eradication Aspirin Trial was a randomised placebo-controlled trial (European Union Drug Regulating Authorities Clinical Trials 2011-003425-96), conducted in United Kingdom primary care using routinely collected clinical data. Consenting participants aged \u2265\u00a060 years prescribed aspirin \u2264\u00a0325\u00a0mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for <jats:italic>H. pylori<\/jats:italic>. Those with a positive test were randomised to receive either a combination of clarithromycin 500\u00a0mg, metronidazole 400\u00a0mg and lansoprazole 30\u00a0mg, or placebos twice daily for 7 days. The primary outcome, time to death or hospitalisation due to peptic ulcer bleeding, was analysed using a Cox proportional hazards model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-3\"><jats:title>Findings<\/jats:title>\n<jats:p>Between 14 September 2012 and 22 November 2017, 30,166 participants underwent <jats:italic>H. pylori<\/jats:italic> breath testing, 5367 had a positive result, 5352 were randomised to an intention-to-treat population of 2677 (eradication) and 2675 (placebo) and followed up for a median of 5.0 years (interquartile range 3.9\u20136.4). Statistical analysis of the primary outcome showed an overall hazard ratio of 0.69 [95% confidence interval 0.38 to 1.25; <jats:italic>p<\/jats:italic>\u2005=\u20050.22], but there was a significant departure from the proportional hazards assumption (<jats:italic>p<\/jats:italic>\u2005=\u20050.0068), requiring analysis split at the median time to event: 2.5 years. There was a significant reduction in the primary outcome in the eradication treatment group in the first 2.5 years (hazard ratio 0.35, 95% confidence interval 0.14 to 0.89; <jats:italic>p<\/jats:italic>\u2005=\u20050.028) but not the second period (hazard ratio 1.31, 95% confidence interval 0.55 to 3.11). The number needed to treat (first period) was 238 (95% confidence interval 184 to 1661). Results in the first 2.5 years remained significant when accounting for the competing risk of death (<jats:italic>p<\/jats:italic>\u2005=\u20050.028). During the study period, 657 participants died (306 in the eradication group and 351 in the controls group; hazard ratio 0.86, 95% confidence interval 0.74 to 1.01; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.058). Malignancy was the most common cause of death and largely accounted for the numerical difference between the treatment groups.<\/jats:p>\n<jats:p>A health economic analysis found proactive screening not cost-effective, since the monetised benefits of the intervention in preventing a peptic ulcer bleed failed to outweigh the costs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-4\"><jats:title>Interpretation<\/jats:title>\n<jats:p><jats:italic>Helicobacter pylori<\/jats:italic> eradication protects against aspirin-associated peptic ulcer bleeding, but this may not be sustained or cost-effective when applied non-selectively to our study population. The possibility that <jats:italic>H. pylori<\/jats:italic> eradication, on a background of aspirin use, might affect death from malignancies warrants further evaluation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-5\"><jats:title>Limitations and future work<\/jats:title>\n<jats:p>Studying subjects already established on aspirin probably contributed to the low event rate. A future study should investigate subjects starting on aspirin when the event rate is higher.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-6\"><jats:title>Trial registration<\/jats:title>\n<jats:p>This trial is registered as ISRCTN10134725; ClinicalTrials.gov number NCT01506986.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"abs1-7\"><jats:title>Funding<\/jats:title>\n<jats:p>This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09\/55\/52) and is published in full in <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 29, No. 42. See the NIHR Funding and Awards website for further award information.<\/jats:p>\n<\/jats:sec>","DOI":"10.3310\/llkf7871","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:11:16Z","timestamp":1755864676000},"page":"1-62","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Eradication of Helicobacter pylori for prevention of aspirin-associated peptic ulcer bleeding in adults over 65 years: the HEAT RCT"],"prefix":"10.3310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-1017","authenticated-orcid":true,"given":"CJ","family":"Hawkey","sequence":"first","affiliation":[{"name":"Simple Trials for Academic Research Unit, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-4438","authenticated-orcid":true,"given":"Anthony 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