Search

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.

Epidemiological studies of patients taking prescribed non-steroidal anti-inflammatory drugs (NSAIDs) show that these drugs are associated with a three to 10-fold increased risk of bleeding, perforation, hospitalisation and death.1 Primary studies and meta-analyses also show that NSAIDs differ in their risk. Ibuprofen is consistently associated with lower risks than the group as a whole whereas other NSAIDs such as piroxicam and azapropazone seem to be associated with relatively high risks. In recent years a number of NSAIDs have become available over the counter. This may partly reflect patent expiry, anticipation of a new generation of NSAIDs (COX-2 selective or NO-NSAIDs) and recognition that the absolute risks of short term, low dose treatment are relatively low. The problem has been to assess the safety of drugs in this setting. In their study Strom et al have attempted to quantify the risks of over the counter naproxen sodium by reference to a prescribing situation that tried to replicate intended patterns of over the counter use. Information was gathered from the Computerized On-Line Medical Pharmaceutical Analysis and Surveillance System (COMPASS) database for Michigan and Ohio, USA. Patients were …

Platelet responses to several agonists and combinations of agonists have been measured in whole blood from healthy volunteers. We have determined the effects of once daily treatment for five days with plain aspirin 300mg, plain aspirin 75mg, enteric coated aspirin 300mg or placebo. Measurements were made of platelet aggregation (using a platelet counting technique) and the release reaction (14C-5HT release from pre-labelled platelets). The extents of these responses before aspirin administration depended on the agonist used. ADP, adrenaline and PAF failed to induce any 14C-5HT release in most subjects, but combinations of these agonists acted synergistically to produce extensive 14C-5HT release. All three aspirin preparations reduced the extent of the platelet responses to most agonists: platelet aggregation induced by collagen, ristocetin and arachidonate and 14C-5HT release induced by collagen, streptokinase, and various combinations of ADP, adrenaline and PAF. None of the preparations had any effect on the aggregation that occurred in the absence of an agonist (spontaneous aggregation), but they all reduced streptokinase-induced aggregation to control (spontaneous) levels, and abolished the 14C-5HT release induced by arachidonate and by ristocetin. All three aspirin preparations were equally effective after two daily doses. No further inhibition of platelet responses was obtained after five daily doses. Plain aspirin 300 mg achieved its maximal effect after only a single dose, but enteric coated aspirin 300mg (and sometimes plain aspirin 75mg) produced sub-maximal inhibition after only a single dose. Parallel investigations on the effects of these aspirin regimes on gastric mucosal prostaglandin E2 synthesis and gastroduodenal mucosal injury were performed. These results will be reported separately. © 1997 Elsevier Science Ltd