The Helicobacter Eradication Aspirin Trial (HEAT): A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care.
BACKGROUND
Clinical trials measuring the effect of an intervention on clinical outcomes are more influential than those investigating surrogate measures but are costly. We developed methods to reduce costs substantially by using existing data in primary care systems, to ask whether Helicobacter pylori eradication would reduce the incidence of hospitalisation for ulcer bleeding in aspirin users.


METHODS
The Helicobacter Eradication Aspirin Trial (HEAT) is a National Institute of Health Research-funded, double-blind placebo controlled randomised trial of the effects of H. pylori eradication on subsequent ulcer bleeding in infected individuals taking aspirin daily, conducted in practices across the whole of England, Wales and Northern Ireland. A bespoke web-based trial management system developed for the trial (and housed within the secure NHS Data Network) communicates directly with the HEAT Toolkit software downloaded at participating practices, which issues queries searching entry criteria (≥ 60 years, on chronic aspirin ≤ 325 mg daily, not on anti-ulcer therapy or non-steroidal anti-inflammatory drugs) for GP review of eligibility. Trial participation is invited using a highly secure automated online mail management system. Interested patients are seen once for consent and breath testing. Those with a positive test are randomised to eradication treatment (lansoprazole, clarithromycin, metronidazole) or placebo, with drug sent by post. Events are tracked by upload of accumulating information in the GP database, patient contact, review of National Hospital Episode Statistics and Office of National Statistics data.


RESULTS
HEAT is the largest Clinical Research Network-supported drug trial, with 115,660 invitation letters sent from 850 practices, 22,922 volunteers, and 3038 H. pylori positive patients randomised to active or placebo treatment after 2.5 years of recruitment. 178 practices have performed their first follow-up data search to identify 21 potential endpoints to date.


CONCLUSIONS
HEAT is important medically, because aspirin is so widely used, and methodologically, as a successful trial would show that large-scale studies of important clinical outcomes can be conducted at a fraction of the cost of those conducted by industry, which in turn will help to ensure that trials of primarily medical rather than commercial interest can be conducted successfully in the UK.
University of Nottingham, UK.
Jennifer S
JS
Dumbleton
University of Nottingham, UK.
Anthony J
AJ
Avery
University of Nottingham, UK.
Carol
C
Coupland
University of Oxford, UK.
F D Richard
FD
Hobbs
University of Nottingham, UK.
Denise
D
Kendrick
University of Southampton, UK.
Michael V
MV
Moore
TCR Nottingham Ltd., UK.
Clive
C
Morris
University of Durham, UK.
Greg P
GP
Rubin
University of Nottingham, UK.
Murray D
MD
Smith
University of Nottingham, UK.
Diane J
DJ
Stevenson
University of Nottingham, UK.
Chris J
CJ
Hawkey
D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use*; D060740:Disease Eradication; D016998:Helicobacter / Q000187:drug effects*; D006801:Humans; D010349:Patient Compliance; D011320:Primary Health Care; D018401:Sample Size; D016896:Treatment Outcome
D001241:Aspirin
Aspirin; Bleed; Clinical trial; Helicobacter pylori; Ulcer