Atorvastatin in Factorial with Omega-3 fatty acid Risk Reduction in Diabetes

…in an academic collaboration with

Trial DesignTrial 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 CommitteeOverall responsibility for scientific, professional

and operational conduct of the study

Diabetes Trials UnitStudy Design and Protocol Dev.Co-ordinating CentreInvestigator agreementsEthical/regulatory approvalData collection and managementProtocol/clinical queriesStatistical analysis/publication

Pfizer UKProtocol development Regulatory aspectsStudy medication On-site MonitoringSAE reporting

DTU CentralLaboratory

70 Clinical Centres

Trial Organisation

AimsAimsTo 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 CriteriaInclusion 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 CriteriaExclusion Criteria Taking prescribed lipid lowering therapy

Triglycerides ≥8.0 mmol/L

Have specific contraindications toatorvastatin or omega-3 PUFA

Have participated in a clinical trialwithin the last 3 months

Are pregnant or lactating females

Atorvastatin Placebo 500Omega-3 Omega-3 Omega-3

(250) (250)

Atorvastatin Placebo 500

Placebo Placebo Placebo(250) (250)

500 500 1,000Atorvastatin Placebo patients

in total

Atorvastatin (20 mg )

Omega-3PUFA (1.8 g)

2 x 2 Factorial Randomisation2 x 2 Factorial Randomisation

Primary ObjectivesPrimary 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 ObjectivesSecondary 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 adherenceat 16 weeks and at one year

Health economic assessmentat 16 weeks and at one year

Visit ScheduleVisit ScheduleVisit 1: week -2 Recruitment

Visit 2: week 0 Randomisation

Visit 3: week 16 Four month evaluation

Visit 4: week 18 Additional medication*Adherence study

Visit 5: week 32 Routine Follow up

Visit 6: week 52 One year evaluationEnd 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:

• Email: aforrd@dtu.ox.ac.uk

• Phone: 01865 857 246

• Fax: 01865 857 256

• Web site:www.dtu.ox.ac.uk/aforrd

Trial ScheduleTrial Schedule