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

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

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Trial Organisation
Steering Committee Overall responsibility for
scientific, professionaland 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
70 Clinical Centres
DTU CentralLaboratory
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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

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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

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Exclusion 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

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2 x 2 Factorial Randomisation
Atorvastatin (20 mg )
Atorvastatin Placebo 500 Omega-3 Omega-3
Omega-3 (250) (250) Atorvastatin
Placebo 500 Placebo Placebo
Placebo (250) (250) 500 500 1,000 Atorvastatin
Placebo patients in total
Omega-3PUFA (1.8 g)
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Primary Objectives

• Proportion of subjects whose LDL levels arelt2.6
  mmol/L at four months
• Proportion of subjects whose triglycerides
  arelt1.5 mmol/L at four months

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Secondary Objectives

• Proportion of subjects with LDL levelslt2.6
  mmol/L at one year
• Proportion of subjects with triglycerideslt1.5
  mmol/L at one year
• Proportion () of subjects with estimated
  ten-year CHD risk lt15 at 16 weeks and one year
• Study medication adherenceat 16 weeks and at one
  year
• Health economic assessmentat 16 weeks and at one
  year

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Visit Schedule

• Visit 1 week -2 Recruitment
• Visit 2 week 0 Randomisation
• Visit 3 week 16 Four month evaluation
• Visit 4 week 18 Additional medication Adherenc
  e study
• Visit 5 week 32 Routine Follow up
• Visit 6 week 52 One 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.

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Trial Schedule

• 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_at_dtu.ox.ac.uk
• Phone [phone]
• Fax [phone]
• Web site www.dtu.ox.ac.uk/aforrd