Clinical trial NCT00327418: CARDS Is Designed To Show If Lowering Cholesterol With Atorvastatin In Type 2 Diabetics Without CV Disease Reduces The Risk Of CV Events
Official title: A Double Blind Placebo Controlled Study of Atorvastatin as Prevention of CHD in High Risk Patients With Non-Insulin Dependent Diabetes Mellitus (Collaborative Atorvastatin Study - CARDS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Coronary Event
Cerebrovascular Accident
Coronary Artery Bypass Graft
Angina, Unstable
Revascularization
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Diabetes UK
name: Department of Health, United Kingdom
First posted: 2006-05-18
Enrollment: 2800
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A study to assess the efficacy of once daily atorvastatin 10 mg versus placebo on cardiovascular endpoints in patients with non-insulin-dependent diabetes mellitus (NIDDM) who have a history of either hypertension, retinopathy, microalbuminuria, macroalbuminuria, or who currently smoke, but who do not have established corornary heart disease or other macrovascular disease.


Eligibility criteria: Inclusion Criteria:

Patients must have a documented history of at least one of the following:

* Hypertension (defined as systolic blood pressure 140 mmHg or a diastolic blood pressure 90 mmHg (defined as the disapperance of all sound \[Korotkoff Phase V\] or receiving anti-hypertensive treatment. Blood pressure should be measured after sitting the patient quietly for 3 minutes).
* Retinopathy (defined as any of the following; non-proliferative retinopathy, pre-pre-proliferative retinopathy, proliferative retinopathy, maculopathy, advanced diabetic eye disease or history of photocoagulation).
* Microalbuminuria (defined as either, Albumin creatinine ratio \> than = to 2.5 mg/mmol, or Albumin excretion rate on a timed collection \> than = to 20 mcg/min (\> than = to 30 mg/24hrs) on two successive occasions, or a positive micral or other strip test).
* Macroalbuminuria (defined as either; Albustix or other dipstick evidence of gross proteinuria, Albumin creatinine ratio \> than = to 25 mg/mmol; or Albumin excretion rate on a timed collection \> than = 200 mcg/min (\> than = 300 mg/24hrs) on two sucessive occasions).
* Current smoker

Exclusion Criteria:

* Type I Diabetes Mellitus
* Any major Coronary event prior to entry into the study

Primary outcomes:
measure: Time from randomization to the occurrence of a primary clinical endpoint
measure: i.e. major coronary event or CABG or other coronary revascularization procedure
measure: or unstable angina or resuscitated cardiac arrest or stroke.
Secondary outcomes:
measure: The incidence rate of a primary clinical and endpoint; the time from randomization
measure: to the occurrence of and the incidence rate of other parameters e.g. total
measure: mortality, any cardiovascular event, new PVD etc. and the percent change from
measure: baseline in various lipid and lipoprotein parameters.
Other outcomes:
Locations:
city: Fosterhill
country: United Kingdom
facility: Pfizer Investigational Site
state: Aberdeen
city: Irvine
country: United Kingdom
facility: Pfizer Investigational Site
state: Ayrshire
city: Midsomer Norton
country: United Kingdom
facility: Pfizer Investigational Site
state: Bath
city: Reading
country: United Kingdom
facility: Pfizer Investigational Site
state: Berkshire
city: Slough
country: United Kingdom
facility: Pfizer Investigational Site
state: Berkshire
city: Maidenhead
country: United Kingdom
facility: Pfizer Investigational Site
state: Berskhire
city: Edgbaston
country: United Kingdom
facility: Pfizer Investigational Site
state: Birmingham
city: Frenchay
country: United Kingdom
facility: Pfizer Investigational Site
state: Bristol
city: Llanishen
country: United Kingdom
facility: Pfizer Investigational Site
state: Cardiff
city: Wrexham
country: United Kingdom
facility: Pfizer Investigational Site
state: Clwydd
city: Bocastle
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Falmouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Fowey
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Penzance
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Penzance
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Redruth
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Saltash
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: St. Austell
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Truro
country: United Kingdom
facility: Pfizer Investigational Site
state: Cornwall
city: Chesterfield
country: United Kingdom
facility: Pfizer Investigational Site
state: Derbyshire
city: Crownhill, Plymouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Devon
city: Plymouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Devon
city: Plympton
country: United Kingdom
facility: Pfizer Investigational Site
state: Devon
city: Bournemouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Dorset
city: Bournemouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Dorset
city: Epping
country: United Kingdom
facility: Pfizer Investigational Site
state: Essex
city: Southend on Sea
country: United Kingdom
facility: Pfizer Investigational Site
state: Essex
city: Langside
country: United Kingdom
facility: Pfizer Investigational Site
state: Glasgow
city: Portsmouth
country: United Kingdom
facility: Pfizer Investigational Site
state: Hampshire
city: Southampton
country: United Kingdom
facility: Pfizer Investigational Site
state: Hampshire
city: Titchfield
country: United Kingdom
facility: Pfizer Investigational Site
state: Hampshire
city: Hemel Hempstead
country: United Kingdom
facility: Pfizer Investigational Site
state: Hertfordshire
city: Watford
country: United Kingdom
facility: Pfizer Investigational Site
state: Hertfordshire
city: Ryde
country: United Kingdom
facility: Pfizer Investigational Site
state: Isle of Wight
city: Gillingham
country: United Kingdom
facility: Pfizer Investigational Site
state: Kent
city: Hildenborough
country: United Kingdom
facility: Pfizer Investigational Site
state: Kent
city: Tunbridge Wells
country: United Kingdom
facility: Pfizer Investigational Site
state: Kent
city: Bolton
country: United Kingdom
facility: Pfizer Investigational Site
state: Lancashire
city: Ormskirk
country: United Kingdom
facility: Pfizer Investigational Site
state: Lancashire
city: Waterloo
country: United Kingdom
facility: Pfizer Investigational Site
state: Liverpool
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
state: M15 6sx
city: Ashford
country: United Kingdom
facility: Pfizer Investigational Site
state: Middlesex
city: Southall
country: United Kingdom
facility: Pfizer Investigational Site
state: Middlesex
city: Scunthorpe
country: United Kingdom
facility: Pfizer Investigational Site
state: North Lincolnshire
city: Harrogate
country: United Kingdom
facility: Pfizer Investigational Site
state: North Yorkshire
city: Northallerton
country: United Kingdom
facility: Pfizer Investigational Site
state: North Yorkshire
city: Sutton-in-Ashfield
country: United Kingdom
facility: Pfizer Investigational Site
state: Nottinghamshire
city: Worksop
country: United Kingdom
facility: Pfizer Investigational Site
state: Nottinghamshire
city: Huthwaite
country: United Kingdom
facility: Pfizer Investigational Site
state: Nottingham
city: Headington
country: United Kingdom
facility: Pfizer Investigational Site
state: Oxford
city: Haverfordwest
country: United Kingdom
facility: Pfizer Investigational Site
state: Pembrokeshire
city: Haverfordwest
country: United Kingdom
facility: Pfizer Investigational Site
state: Pembrokeshire
city: Shrewsbury
country: United Kingdom
facility: Pfizer Investigational Site
state: Shropshire
city: Frome
country: United Kingdom
facility: Pfizer Investigational Site
state: Somerset
city: Weston-Super-Mare
country: United Kingdom
facility: Pfizer Investigational Site
state: Somerset
city: Sheffield
country: United Kingdom
facility: Pfizer Investigational Site
state: South Yorkshire
city: Sheffield
country: United Kingdom
facility: Pfizer Investigational Site
state: South Yorkshire
city: Sheffield
country: United Kingdom
facility: Pfizer Investigational Site
state: South Yorkshire
city: Stirling
country: United Kingdom
facility: Pfizer Investigational Site
state: Stirlingshire
city: Carshalton
country: United Kingdom
facility: Pfizer Investigational Site
state: Surrey
city: Epsom
country: United Kingdom
facility: Pfizer Investigational Site
state: Surrey
city: Pontarddulais
country: United Kingdom
facility: Pfizer Investigational Site
state: Swansea
city: Dundee
country: United Kingdom
facility: Pfizer Investigational Site
state: Tayside
city: Dundee
country: United Kingdom
facility: Pfizer Investigational Site
state: Tayside
city: Hetton le Hole
country: United Kingdom
facility: Pfizer Investigational Site
state: Tyne & Wear
city: Gateshead
country: United Kingdom
facility: Pfizer Investigational Site
state: Tyne and Wear
city: Nuneaton
country: United Kingdom
facility: Pfizer Investigational Site
state: Warwickshire
city: Rugby
country: United Kingdom
facility: Pfizer Investigational Site
state: Warwickshire
city: Lyndon
country: United Kingdom
facility: Pfizer Investigational Site
state: West Bromwich, West Midlands
city: Livingston
country: United Kingdom
facility: Pfizer Investigational Site
state: West Lothian
city: Wolverhampton
country: United Kingdom
facility: Pfizer Investigational Site
state: West Midlands
city: Crawley
country: United Kingdom
facility: Pfizer Investigational Site
state: West Sussex
city: Crawley
country: United Kingdom
facility: Pfizer Investigational Site
state: West Sussex
city: Haywards Heath
country: United Kingdom
facility: Pfizer Investigational Site
state: West Sussex
city: Corsham
country: United Kingdom
facility: Pfizer Investigational Site
state: Wiltshire
city: Trowbridge
country: United Kingdom
facility: Pfizer Investigational Site
state: Wiltshire
city: Trowbridge
country: United Kingdom
facility: Pfizer Investigational Site
state: Wiltshire
city: Warminster
country: United Kingdom
facility: Pfizer Investigational Site
state: Wiltshire
city: Westbury
country: United Kingdom
facility: Pfizer Investigational Site
state: Wiltshire
city: York
country: United Kingdom
facility: Pfizer Investigational Site
state: Yorkshire
city: Ayr
country: United Kingdom
facility: Pfizer Investigational Site
city: Ayr
country: United Kingdom
facility: Pfizer Investigational Site
city: Bath
country: United Kingdom
facility: Pfizer Investigational Site
city: Bath
country: United Kingdom
facility: Pfizer Investigational Site
city: Bath
country: United Kingdom
facility: Pfizer Investigational Site
city: Bath
country: United Kingdom
facility: Pfizer Investigational Site
city: Bath
country: United Kingdom
facility: Pfizer Investigational Site
city: Belfast
country: United Kingdom
facility: Pfizer Investigational Site
city: Belfast
country: United Kingdom
facility: Pfizer Investigational Site
city: Belfast
country: United Kingdom
facility: Pfizer Investigational Site
city: Birmingham
country: United Kingdom
facility: Pfizer Investigational Site
city: Birmingham
country: United Kingdom
facility: Pfizer Investigational Site
city: Birmingham
country: United Kingdom
facility: Pfizer Investigational Site
city: Cambridge
country: United Kingdom
facility: Pfizer Investigational Site
city: Chippenham, Wiltshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Co. Dublin
country: United Kingdom
facility: Pfizer Investigational Site
city: Coventry
country: United Kingdom
facility: Pfizer Investigational Site
city: Derby
country: United Kingdom
facility: Pfizer Investigational Site
city: Dewsbury
country: United Kingdom
facility: Pfizer Investigational Site
city: Dublin 8
country: United Kingdom
facility: Pfizer Investigational Site
city: Dumfries
country: United Kingdom
facility: Pfizer Investigational Site
city: East Kilbride
country: United Kingdom
facility: Pfizer Investigational Site
city: Edinburgh
country: United Kingdom
facility: Pfizer Investigational Site
city: Edinburgh
country: United Kingdom
facility: Pfizer Investigational Site
city: Glasgow
country: United Kingdom
facility: Pfizer Investigational Site
city: Glasgow
country: United Kingdom
facility: Pfizer Investigational Site
city: Glasgow
country: United Kingdom
facility: Pfizer Investigational Site
city: Hartlepool
country: United Kingdom
facility: Pfizer Investigational Site
city: Hertfordshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Hertfordshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Inverness
country: United Kingdom
facility: Pfizer Investigational Site
city: Leicester
country: United Kingdom
facility: Pfizer Investigational Site
city: Liverpool
country: United Kingdom
facility: Pfizer Investigational Site
city: Llantrisant
country: United Kingdom
facility: Pfizer Investigational Site
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Pfizer Investigational Site
city: Nottingham
country: United Kingdom
facility: Pfizer Investigational Site
city: Oldham
country: United Kingdom
facility: Pfizer Investigational Site
city: Paisley
country: United Kingdom
facility: Pfizer Investigational Site
city: Pontefract
country: United Kingdom
facility: Pfizer Investigational Site
city: Southampton
country: United Kingdom
facility: Pfizer Investigational Site
city: Swansea
country: United Kingdom
facility: Pfizer Investigational Site
city: Swansea
country: United Kingdom
facility: Pfizer Investigational Site
city: Wakefield
country: United Kingdom
facility: Pfizer Investigational Site
city: Wigan
country: United Kingdom
facility: Pfizer Investigational Site
city: Wiltshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Wiltshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Wiltshire
country: United Kingdom
facility: Pfizer Investigational Site
city: Wishaw
country: United Kingdom
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Neil HA, DeMicco DA, Luo D, Betteridge DJ, Colhoun HM, Durrington PN, Livingstone SJ, Fuller JH, Hitman GA; CARDS Study Investigators. Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006 Nov;29(11):2378-84. doi: 10.2337/dc06-0872.
citation: Vogt L, Bangalore S, Fayyad R, Melamed S, Hovingh GK, DeMicco DA, Waters DD. Atorvastatin Has a Dose-Dependent Beneficial Effect on Kidney Function and Associated Cardiovascular Outcomes: Post Hoc Analysis of 6 Double-Blind Randomized Controlled Trials. J Am Heart Assoc. 2019 May 7;8(9):e010827. doi: 10.1161/JAHA.118.010827.
citation: Bangalore S, Fayyad R, DeMicco DA, Colhoun HM, Waters DD. Body Weight Variability and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus. Circ Cardiovasc Qual Outcomes. 2018 Nov;11(11):e004724. doi: 10.1161/CIRCOUTCOMES.118.004724.
citation: Ports WC, Fayyad R, DeMicco DA, Laskey R, Wolk R. Effectiveness of Lipid-Lowering Statin Therapy in Patients With and Without Psoriasis. Clin Drug Investig. 2017 Aug;37(8):775-785. doi: 10.1007/s40261-017-0533-0.
citation: Deedwania PC, Pedersen TR, DeMicco DA, Breazna A, Betteridge DJ, Hitman GA, Durrington P, Neil A; TNT, CARDS and IDEAL Steering Committees and Investigators. Differing predictive relationships between baseline LDL-C, systolic blood pressure, and cardiovascular outcomes. Int J Cardiol. 2016 Nov 1;222:548-556. doi: 10.1016/j.ijcard.2016.07.201. Epub 2016 Jul 30.
citation: Kaasenbrood L, Poulter NR, Sever PS, Colhoun HM, Livingstone SJ, Boekholdt SM, Pressel SL, Davis BR, van der Graaf Y, Visseren FL; CARDS, ALLHAT, and ASCOT Investigators. Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study. Circ Cardiovasc Qual Outcomes. 2016 May;9(3):213-21. doi: 10.1161/CIRCOUTCOMES.115.001980. Epub 2016 May 11.
citation: Soedamah-Muthu SS, Livingstone SJ, Charlton-Menys V, Betteridge DJ, Hitman GA, Neil HA, Bao W, DeMicco DA, Preston GM, Fuller JH, Stehouwer CD, Schalkwijk CG, Durrington PN, Colhoun HM; CARDS Investigators. Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial. Diabetologia. 2015 Jul;58(7):1494-502. doi: 10.1007/s00125-015-3586-8. Epub 2015 Apr 22.
citation: Deshmukh HA, Colhoun HM, Johnson T, McKeigue PM, Betteridge DJ, Durrington PN, Fuller JH, Livingstone S, Charlton-Menys V, Neil A, Poulter N, Sever P, Shields DC, Stanton AV, Chatterjee A, Hyde C, Calle RA, DeMicco DA, Trompet S, Postmus I, Ford I, Jukema JW, Caulfield M, Hitman GA. Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a). J Lipid Res. 2012 May;53(5):1000-1011. doi: 10.1194/jlr.P021113. Epub 2012 Feb 24.
citation: Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Charlton-Menys V, DeMicco DA, Fuller JH; CARDS Investigators. Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis. 2009 Nov;54(5):810-9. doi: 10.1053/j.ajkd.2009.03.022. Epub 2009 Jun 21.
citation: Charlton-Menys V, Betteridge DJ, Colhoun H, Fuller J, France M, Hitman GA, Livingstone SJ, Neil HA, Newman CB, Szarek M, DeMicco DA, Durrington PN. Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS). Diabetologia. 2009 Feb;52(2):218-25. doi: 10.1007/s00125-008-1176-8. Epub 2008 Oct 30.
citation: Newman CB, Szarek M, Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Demicco DA, Auster S, Fuller JH; Cards Investigators. The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS). Diab Vasc Dis Res. 2008 Sep;5(3):177-83. doi: 10.3132/dvdr.2008.029.