Diabetes Trials Unit University of Oxford

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Diabetes Trials UnitUniversity of
Oxford WebSite http//www.dtu.ox.ac.uk/lds
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Trial Design

• Academic, investigator-led, clinical-outcome
  trial
• 5,000 type 2 diabetic patients, aged 40 to 75
  years
• Primary intervention - no clinical evidence of
  CHD
• Double-blind, placebo-controlled, 2x2 factorial
  randomisation
• Cerivastatin 0.4 mg/day, micronised fenofibrate
  200 mg/day
• 30 UK clinical centres, five year follow-up
• Funded by an educational grant from Bayer

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Exclusion Criteria

• Thought to require lipid-lowering therapy
• LDL cholesterol gt4.1 mmol/L (160 mg/dL)
• Triglyceride gt4.5 mmol/L (400 mg/dL)
• Impaired renal/hepatic function
• History of myopathy or cholelithiasis
• Life threatening disease
• Pregnancy

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Subject Characteristics at Entry
n1616 (May 2000) Mean SD Male 67 Caucasian 90
Current smoker 14 Age (y) 60 8 BMI
(kg/m2) 30.3 6.0 Blood pressure (mm
Hg) 144/83 19/11 Duration of diabetes (y) 8 4 to
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Median, IQR
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Baseline Biochemistry
n1616 (May 2000) Mean SD Total cholesterol
(mmol/L) 5.0 0.8 HDL cholesterol
(mmol/L) 1.2 0.3 LDL cholesterol
(mmol/L) 3.1 0.7 Triglyceride (mmol/L) 1.5 0.9
to 2.6 HbA1c () 8.3 7.3 to 9.4
Median, IQR
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Baseline Biochemistry
n1616 (May 2000) Mean SD Total cholesterol
(mg/dL) 195 31 HDL cholesterol (mg/dL) 47 12 LDL
cholesterol (mg/dL) 121 27 Triglyceride
(mg/dL) 133 80 to 231 HbA1c () 8.3 7.3 to 9.4
Median, IQR
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2 x 2 Factorial Randomisation
Cerivastatin arm
Cerivastatin Placebo 2,500 Fenofibrate
Fenofibrate Fenofibrate (1250) (1250)
Cerivastatin Placebo 2,500 Placebo Placebo
Placebo (1250) (1250) 2,500 2,500 5,000 Ceri
vastatin Placebo patients in total
Fenofibrate arm
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Composite Primary Endpoint
First occurrence of

• Fatal myocardial infarction including sudden
  death
• or
• Non-fatal myocardial infarction
• or
• Coronary or peripheral artery revascularisation

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Secondary Outcomes

• Fatal or non-fatal stroke
• Coronary syndromes(fatal or non-fatal myocardial
  infarction,stable and unstable angina)
• Heart failure
• All cause mortality
• Retinal photocoagulation
• Renal failure

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Surrogate Outcomes

• Microalbuminuria
• Digital electrocardiographic changes
• Visual acuity
• Lipid profile

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Health Economics

• Four monthly assessment of
• Time off work
• Concomitant drug treatment
• Hospital admissions/procedures
• Health resource utilisation
• EuroQoL-5 (SF-36 at entry at 5 years)

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Power of the Study

• Allocated Allocated Power at
• cerivastatin placebo 2plt0.01
• Number randomised 2,500 2,500
• Number evaluable (96) 2,400 2,400
• LDS primary endpoint 179 255 90

assuming a 30 reduction in events with
cerivastatinand adjusting for factorial design
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Schedule
Study commenced 1999 Two year recruitment
until 2001 Four monthly follow up ofall subjects
for five years Closeout and publication in 2006
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Conclusions

• The LDS will demonstrate whether lipid lowering
  drug therapy reduces cardiovascular events among
  type 2 patients, many of whom would not be
  treated on the basis of the current Joint
  European Recommendations
• The LDS will provide an evidence-base for the use
  of statin therapy, fibrate therapy, and
  combination therapy, for the primary prevention
  of cardiovascular disease in people with type 2
  diabetes