Recruitment to a large scale randomised controlled clinical trial in primary care: the Helicobacter Eradication Aspirin Trial (HEAT)

Stevenson, Diane J.; Avery, Anthony J.; Coupland, Carol; Hobbs, F. D. Richard; Kendrick, Denise; Moore, Michael V.; Morris, Clive; Rubin, Greg P.; Smith, Murray D.; Hawkey, Christopher J.; Dumbleton, Jennifer S.

Abstract

Background: The Helicobacter Eradication Aspirin Trial (HEAT) is a multicentre, double blind, randomised controlled trial investigating whether Helicobacter (H.) pylori eradication reduces hospitalisation for peptic ulcer bleeding. Recruited participants were aged 60 and over and taking aspirin (≤325 mg daily) for at least four months prior to consent. Based on results of a pilot study, a sample size calculation predicted 6600 H. pylori-positive randomised participants would be required, from 33,000 volunteers, recruited from 170,000 invited patients. Methodology was therefore designed for recruitment of large numbers of patients from primary care using a novel electronic search tool, automated mail-out and electronic follow-up. Recruitment started in 2012 and completed in 2017. Methods: All participants were recruited from GP practices, with assistance from the UK Clinical Research Network (UKCRN). H. pylori-positive participants were randomised to one week of eradication treatment or placebo. Recruitment was managed using a bespoke web-based database that communicated directly with a programmed search tool downloaded at participating practices. The primary endpoint is hospitalisation due to peptic ulcer bleeding. The trial will end when 87 adjudicated events have occurred, identified from searches of GP databases, review of secondary care admission data and mortality data, and reported events from randomised participants and GPs. Results: HEAT has recruited participants from 1208 GP practices across the UK. Of the 188,875 invitation letters sent, 38,771 returned expressions of interest. Of these, 30,166 patients were consented to the trial, of whom 5355 H. pylori-positive participants (17.8% of those consented) were randomised. Mean age at consent was 73.1 ± 6.9 (SD) years and 72.2% of participants were male. Of the randomised (H. pylori-positive) participants, 531 have died (as of 17 Sep 2020); none of the deaths was due to trial treatment. Conclusion: The HEAT trial methodology has demonstrated that recruitment of large numbers of patients from primary care is attainable, with the assistance of the UKCRN, and could be applied to other clinical outcomes studies. Trial registration: ClinicalTrials.gov; registration number NCT01506986. Registered on 10 Jan 2012.

• Journal Article Type: Article
• Acceptance Date: Jan 27, 2022
• Online Publication Date: Feb 14, 2022
• Publication Date: Feb 14, 2022
• Deposit Date: Oct 27, 2020
• Publicly Available Date: Feb 14, 2022
• Journal: Trials
• Electronic ISSN: 1745-6215
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 1
• Article Number: 140
• DOI: https://doi.org/10.1186/s13063-022-06054-w
• Keywords: Pharmacology (medical); Medicine (miscellaneous)
• Public URL: https://nottingham-repository.worktribe.com/output/4995173
• Publisher URL: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06054-w
• Additional Information: Received: 23 March 2021; Accepted: 27 January 2022; First Online: 14 February 2022; : ; : REC reference number 11/EM/0434 approved by the East Midlands NRES Committee on 22-Dec-2011. All participants signed an Informed Consent Form approved by the REC Committee prior to any trial procedures.; : Not applicable.; : The authors declare that they have no competing interests.