Atorvastatin in Factorial with Omega-3 fatty acid Risk Reduction in Diabetes …in an academic collaboration with

Trial Design  Collaborative academic and pharmaceutical study  Funded by Pfizer, with data owned, analysed and reported by the University of Oxford Diabetes Trials Unit (DTU)  Multi-centre primary prevention trial in 1,000 patients with type 2 diabetes  Double-blind, placebo-controlled  2 x 2 factorial randomisation to Atorvastatin (Lipitor 20 mg/day) Omega 3 PUFA (Omacor 2g/day)  70 UK clinical centres, one year follow-up

Steering Committee Overall responsibility for scientific, professional and operational conduct of the study Diabetes Trials Unit Study Design and Protocol Dev. Co-ordinating Centre Investigator agreements Ethical/regulatory approval Data collection and management Protocol/clinical queries Statistical analysis/publication Pfizer UK Protocol development Regulatory aspects Study medication On-site Monitoring SAE reporting DTU Central Laboratory 70 Clinical Centres Trial Organisation

Aims To determine the:  Range of estimated CHD risk levels typically seen in people with type 2 diabetes in UK general practice  Proportion whose estimated ten-year CHD risk can be reduced below 15% with a 20 mg of atorvastatin or 1.8 g omega-3 PUFA/day  Degree to which atorvastatin and omega-3 PUFA in combination have additive effects  Extent to which therapy adherence can be enhanced using a simple behavioural intervention

Inclusion Criteria  Aged 18 years and above  Have had type 2 diabetes for at least 3 months  Not known to have had a cardiovascular event  Have provided written informed consent

Exclusion Criteria  Taking prescribed lipid lowering therapy  Triglycerides ≥8.0 mmol/L  Have specific contraindications to atorvastatin or omega-3 PUFA  Have participated in a clinical trial within the last 3 months  Are pregnant or lactating females

AtorvastatinPlacebo 500 Omega-3 Omega-3 Omega-3(250) Atorvastatin Placebo 500 Placebo Placebo Placebo(250) ,000 Atorvastatin Placebopatients in total Atorvastatin (20 mg ) Omega-3 PUFA (1.8 g) 2 x 2 Factorial Randomisation

Primary Objectives  Proportion of subjects whose LDL levels are <2.6 mmol/L at four months  Proportion of subjects whose triglycerides are <1.5 mmol/L at four months

Secondary Objectives  Proportion of subjects with LDL levels <2.6 mmol/L at one year  Proportion of subjects with triglycerides <1.5 mmol/L at one year  Proportion (%) of subjects with estimated ten- year CHD risk <15% at 16 weeks and one year  Study medication adherence at 16 weeks and at one year  Health economic assessment at 16 weeks and at one year

Visit Schedule Visit 1: week-2Recruitment Visit 2: week0Randomisation Visit 3: week16Four month evaluation Visit 4: week18Additional medication* Adherence study Visit 5: week32Routine Follow up Visit 6: week52One year evaluation End of study * Patients whose estimated CHD risk remains greater than 20% at four months will receive an additional tablet containing 20 mg atorvastatin, whilst the remainder will receive an additional placebo tablet, in double-blind fashion.

 Study will commence in 2004  One year recruitment in 70 UK practices  One year follow-up for all subjects  Results expected 2006 Contact: Phone: Fax: Web site: Trial Schedule