1. OPPORTUNITIES FOR RESEARCH IN PRIMARY CARE Jen Dumbleton Clinical Trial Manager University of Nottingham jennifer.dumbleton@nottingham.ac.uk 0115 823 1053 Essex, Herts Valley & Luton Primary Care Forum Meeting, 3 July 2015

2. Update on Existing Research… An ultra simple randomised study to investigate whether a one week course of H. pylori eradication reduces hospitalisation for ulcer bleeding in patients using aspirin

3. 10 15 20 25 30 19981999200020012002200320042005 Millions 200620072008 35 Aspirin vs NSAIDs Aspirin NSAIDs

4. HEAT Hypothesis Ulcer NSAIDs Some bleed Ulcer H. pylori Some bleed Aspirin +

5. HEAT Entry Criteria INCLUSION ≥ 60 years of age Subjects taking aspirin ≤325mg daily who have had 4 or more 28-day prescriptions in the last year. Subjects concurrently using other anti-platelet agents are allowed to enter the study. EXCLUSION Subjects currently prescribed anti-ulcer therapy such as H2-receptor antagonists and proton-pump inhibitors. Subjects currently prescribed oral non-steroidal anti- inflammatory drugs (NSAIDs).

6. Trial Design GP Practices search systems (MIQUEST) for eligible patients Aspirin ≤325mg daily 60+ yo Not prescribed NSAIDs / PPIs Screening Visit with Breath test +ve-ve RANDOMISE (double-blind) Placebo H. pylori eradication treatment Clarithromycin 500mg Metronidazole 400mg Lansoprazole 30mg 2 years’ follow-up (no visits) until 87 endpoints occur

7. >700 GP practices 17,628 consented patients

8. Benefits of taking part Simple study (low workload, ideal for practices new to research). Large team on hand to help with any queries. Assuming all participating patients ultimately undergo eradication, the trial should prevent around 585 hospitalisations and 59 deaths, at a saving of approximately £5.85 million. This potentially makes the trial itself a cost effective therapeutic intervention.

9. We’re excited! Aspirin World’s most famous drug Helps the 2 biggest killers (Western world) Most important issue in prophylaxis of ulcer bleeding Important trial Big question Brings outcomes studies to non-pharma arena Easy to do 1 week treatment No FU Establishes paradigms for future

10. Allopurinol in Ischaemic Heart Disease A new study coming soon…

11. Ischaemic heart disease (IHD) IHD is common with prevalence 4.6% Scotland 3.5% England 4% of men and 0.5% of women have had MI 14% of men and 8% of women age 65-74yrs have had angina IHD is the commonest cause of death in UK 1 in 5 men and 1 in 7 women die of IHD

12. Why might allopurinol help in IHD? Reduces left ventricular hypertrophy diabetes angina Reduces blood pressure Improves arterial stiffness Improves endothelial function* Reduces oxidative stress* Improves exercise time and chest pain in angina * 600mg daily more effective than 300mg daily

13. ALL-HEART study Does allopurinol improve cardiovascular outcomes in patients with IHD? 5,215 patients with IHD Randomised to Allopurinol 600mg daily added to usual care vs Usual care Followed up for average of 4 years Electronic record-linkage Hospitalisations and deaths Annual questionnaire Quality of life Health resource usage Compliance, adverse events, gout flares and skin rashes

14. KEY POINTS -Low workload (search for eligible patients) -Patient visits (1 or 2) performed by CRN or practice nurse -No manual follow-up by practice

15. GP participation 300 GP practices 150 in Scotland, 150 in England Hope to randomise around 15 patients per practice We will make it as easy as possible for practices to participate Study supported by the CRN (service support costs paid for time)

16. Questions? jennifer.dumbleton@nottingham.ac.uk 0115 823 1053