Blood Pressure and Glucose Lowering for the Prevention of Vascular Disease in High Risk Patients With Type 2 Diabetes

NCT00145925 | Completed Phase 3 DMC

• 1 other identifier: ADVANCE
• Study Type: interventional
• Target: 11,140
• Locations: 5 countries
• Sites: 5

Brief Summary

The purpose of this study is to provide information on the risks and benefits of routine blood pressure lowering (regardless of blood pressure level), and intensive lowering of blood glucose levels, in patients with Type 2 diabetes at high risk of cardiovascular events. The major outcomes of the study will be cardiovascular events (heart attack, stroke or dying as a result of cardiovascular disease), as well as new or worsening diabetic eye and kidney disease.

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Type 2; Blood Pressure; Stroke; MI

Outcome Measures

Primary Outcomes (2)

• Composite of non-fatal stroke, non-fatal myocardial infarction or death from any cardiovascular cause

  July 2001 - December 2007

• Composite of new or substantially worsening nephropathy or microvascular eye disease.

  July 2001 - December 2007

Secondary Outcomes (1)

• Includes cerebrovascular disease, coronary heart disease, heart failure, peripheral vascular disease, cardiovascular and all-cause mortality, microalbuminuria, visual deterioration, new or worsening nephropathy, cognitive function, and dementia.

  July 2001 - December 2007

Study Arms (2)

Blood pressure

PLACEBO COMPARATOR

Perindopril indapamide vs placebo

Drug: Perindopril-indapamide

Glucose control

OTHER

Standard versus intensive glucose control

Drug: Gliclazide MR-based glucose lowering

Interventions

Perindopril-indapamide DRUG

Blood pressure

Gliclazide MR-based glucose lowering DRUG

Glucose control

Eligibility Criteria

• Age: 55 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of type 2 diabetes mellitus first made at age 30 years or older
• Age 55 years or older at entry
• Ability to provide informed consent
• A substantially elevated risk of cardiovascular disease, indicated by:
• A history of major macrovascular disease defined as any one of: stroke, myocardial infarction, hospital admission for transient ischaemic attack, hospital admission for unstable angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty (with or without stenting), peripheral revascularisation (angioplasty or surgery) or amputation secondary to vascular disease or
• A history of major microvascular disease defined as any one of nephropathy (albumin:creatinine ratio \>300ug/mg), retinal photocoagulation therapy, proliferative retinopathy (new blood vessels on the disc or elsewhere, vitreous haemorrhage, pre-retinal haemorrhage, or fibrous proliferations on the disc or elsewhere), macular oedema (retinal thickening within one disc diameter of the macular centre) or blindness in either eye (corrected visual acuity 6/60 or worse, persisting for three months or more) not known to be due to non-diabetic causes or
• A first diagnosis of type 2 diabetes made 10 or more years prior to entry or
• Another major risk factor for vascular disease defined as any one of: current daily cigarette smoking, total cholesterol greater than 6.0 mmol/l (with or without cholesterol lowering treatment), HDL cholesterol \<1.0 mmol/l, microalbuminuria (albumin:creatinine ratio 30-300ug/mg) or
• Age 65 years or over

You may not qualify if:

• A definite contraindication to treatment with an ACE inhibitor or a thiazide-like diuretic
• A specific indication for treatment with an ACE inhibitor other than perindopril 2-4 mg daily (see also section 5.2.3) or a thiazide-like diuretic
• A definite and specific indication for treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
• A definite contra-indication to treatment with gliclazide or a haemoglobin A1c control target of 6.5% or less
• A definite indication for long-term full-dose or bed-time insulin therapy
• Participation in a trial within the month prior to the Registration Visit or current participation in another trial
• Other potential reasons for ineligibility include:
• High probability of non-adherence to study treatment or follow-up
• Current clinical instability (e.g. a major cerebral or coronary event or sight-threatening retinopathy or macular oedema within the previous few weeks)
• Life threatening non-vascular disease other than diabetes and its complications
• Moderate or severe dementia
• Major disability that is likely to prevent regular attendance at study clinics
• Final decisions about eligibility were made at the discretion of the study investigator and the potential study participant, in the light of any requirements or guidance from local ethics committees and other regulatory bodies.

Sponsors & Collaborators

• The George Institute: lead
• Institut de Recherches Internationales Servier: collaborator
• University of Sydney: collaborator
• National Health and Medical Research Council, Australia: collaborator

Study Sites (5)

The University of Melbourne

Melbourne, Victoria, 3010, Australia

Location

University of Montreal

Montreal, Quebec, H26 1X2, Canada

Location

Cardiovascular Institute & Fu Wai Hospital

Beijing, Beijing Municipality, 100037, China

Location

The Julius Center for Health Sciences and Primary Care

Utrecht, Utrecht, 3508 BA, Netherlands

Location

Imperial College School of Medicine

London, W2 1PG, United Kingdom

Location

Related Publications (50)

• Rationale and design of the ADVANCE study: a randomised trial of blood pressure lowering and intensive glucose control in high-risk individuals with type 2 diabetes mellitus. Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation. J Hypertens Suppl. 2001 Nov;19(4):S21-8.

  PMID: 11848259 BACKGROUND

• ADVANCE Collaborative Group. ADVANCE--Action in Diabetes and Vascular Disease: patient recruitment and characteristics of the study population at baseline. Diabet Med. 2005 Jul;22(7):882-8. doi: 10.1111/j.1464-5491.2005.01596.x.

  PMID: 15975103 BACKGROUND

• ADVANCE Management Committee. Study rationale and design of ADVANCE: action in diabetes and vascular disease--preterax and diamicron MR controlled evaluation. Diabetologia. 2001 Sep;44(9):1118-20. doi: 10.1007/s001250100612.

  PMID: 11596665 BACKGROUND

• Harris K, Gong J, MacMahon S, Xu Y, Shajahan S, Harrap S, Poulter N, Marre M, Hamet P, Mancia G, Anderson C, Woodward M, Chalmers J. Effect of randomised blood pressure lowering treatment and intensive glucose control on dementia and cognitive decline according to baseline cognitive function and other subpopulations of individuals with type 2 diabetes: Results from the ADVANCE trial. Cereb Circ Cogn Behav. 2024 Dec 5;8:100372. doi: 10.1016/j.cccb.2024.100372. eCollection 2025.

  PMID: 39758508 DERIVED

• Wang N, Harris K, Woodward M, Harrap S, Mancia G, Poulter N, Chalmers J, Rodgers A; PROGRESS and ADVANCE collaborators. Clinical Utility of Short-Term Blood Pressure Measures to Inform Long-Term Blood Pressure Management. Hypertension. 2023 Mar;80(3):608-617. doi: 10.1161/HYPERTENSIONAHA.122.20458. Epub 2022 Dec 5.

  PMID: 36468403 DERIVED

• Ohkuma T, Harris K, Cooper M, Grobbee DE, Hamet P, Harrap S, Mancia G, Marre M, Patel A, Rodgers A, Williams B, Woodward M, Chalmers J; ADVANCE Collaborative Group. Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and Mortality: Results from a Randomized Controlled Trial of ACE Inhibitors. Clin J Am Soc Nephrol. 2022 Aug;17(8):1139-1149. doi: 10.2215/CJN.00180122. Epub 2022 Jul 27.

  PMID: 35896277 DERIVED

• Juraschek SP, Wang D, McEvoy JW, Harrap S, Harris K, Mancia G, Marre M, Neal B, Patel A, Poulter NR, Williams B, Chalmers J, Woodward M, Selvin E. Effects of glucose and blood pressure reduction on subclinical cardiac damage: Results from ADVANCE. Int J Cardiol. 2022 Jul 1;358:103-109. doi: 10.1016/j.ijcard.2022.04.044. Epub 2022 Apr 18.

  PMID: 35439582 DERIVED

• Harris K, Muntner P, Woodward M, Jun M, Oshima M, Gong J, Harrap S, Menard J, Chalmers J. Clinical outcomes by atherosclerotic cardiovascular disease risk score and blood pressure level in high risk individuals with type 2 diabetes. J Hum Hypertens. 2023 Mar;37(3):181-188. doi: 10.1038/s41371-022-00661-5. Epub 2022 Feb 19.

  PMID: 35184142 DERIVED

• Nguyen TN, Harris K, Woodward M, Chalmers J, Cooper M, Hamet P, Harrap S, Heller S, MacMahon S, Mancia G, Marre M, Poulter N, Rogers A, Williams B, Zoungas S, Chow CK, Lindley RI. The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial. Diabetes Care. 2021 Jul;44(7):1622-1629. doi: 10.2337/dc20-2664. Epub 2021 May 25.

  PMID: 34035077 DERIVED

• Wang N, Harris K, Chalmers J, Harrap S, Mancia G, Marre M, Poulter N, Tzourio C, Williams B, Zoungas S, Woodward M, Rodgers A. Combination blood pressure lowering in the presence or absence of background statin and aspirin therapy: a combined analysis of PROGRESS and ADVANCE Trials. J Hypertens. 2021 Aug 1;39(8):1689-1696. doi: 10.1097/HJH.0000000000002862.

  PMID: 33883461 DERIVED

• Gong J, Harris K, Hackett M, Peters SAE, Brodaty H, Cooper M, Hamet P, Harrap S, Mancia G, MacMahon S, Chalmers J, Woodward M. Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial. Diabetes Obes Metab. 2021 Aug;23(8):1775-1785. doi: 10.1111/dom.14391. Epub 2021 May 4.

  PMID: 33783955 DERIVED

• Tham YK, Jayawardana KS, Alshehry ZH, Giles C, Huynh K, Smith AAT, Ooi JYY, Zoungas S, Hillis GS, Chalmers J, Meikle PJ, McMullen JR. Novel Lipid Species for Detecting and Predicting Atrial Fibrillation in Patients With Type 2 Diabetes. Diabetes. 2021 Jan;70(1):255-261. doi: 10.2337/db20-0653. Epub 2020 Oct 28.

  PMID: 33115826 DERIVED

• Harris K, Oshima M, Sattar N, Wurtz P, Jun M, Welsh P, Hamet P, Harrap S, Poulter N, Chalmers J, Woodward M. Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study. Diabetologia. 2020 Aug;63(8):1637-1647. doi: 10.1007/s00125-020-05162-z. Epub 2020 May 8.

  PMID: 32385604 DERIVED

• Tian J, Ohkuma T, Cooper M, Harrap S, Mancia G, Poulter N, Wang JG, Zoungas S, Woodward M, Chalmers J. Effects of Intensive Glycemic Control on Clinical Outcomes Among Patients With Type 2 Diabetes With Different Levels of Cardiovascular Risk and Hemoglobin A1c in the ADVANCE Trial. Diabetes Care. 2020 Jun;43(6):1293-1299. doi: 10.2337/dc19-1817. Epub 2020 Mar 19.

  PMID: 32193249 DERIVED

• Oshima M, Jun M, Ohkuma T, Toyama T, Wada T, Cooper ME, Hadjadj S, Hamet P, Harrap S, Mancia G, Marre M, Williams B, Chalmers J, Woodward M, Perkovic V; ADVANCE Collaborative Group. The relationship between eGFR slope and subsequent risk of vascular outcomes and all-cause mortality in type 2 diabetes: the ADVANCE-ON study. Diabetologia. 2019 Nov;62(11):1988-1997. doi: 10.1007/s00125-019-4948-4. Epub 2019 Jul 13.

  PMID: 31302707 DERIVED

• Ohkuma T, Jun M, Rodgers A, Cooper ME, Glasziou P, Hamet P, Harrap S, Mancia G, Marre M, Neal B, Perkovic V, Poulter N, Williams B, Zoungas S, Chalmers J, Woodward M; ADVANCE Collaborative Group. Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus. Hypertension. 2019 Jan;73(1):84-91. doi: 10.1161/HYPERTENSIONAHA.118.12060.

  PMID: 30571562 DERIVED

• Thomas MC, Woodward M, Li Q, Pickering R, Tikellis C, Poulter N, Cooper ME, Marre M, Zoungas S, Chalmers J; ADVANCE Collaborative Group. Relationship Between Plasma 8-OH-Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial. J Am Heart Assoc. 2018 Jun 30;7(13):e008226. doi: 10.1161/JAHA.117.008226.

  PMID: 29960985 DERIVED

• Welsh P, Rankin N, Li Q, Mark PB, Wurtz P, Ala-Korpela M, Marre M, Poulter N, Hamet P, Chalmers J, Woodward M, Sattar N. Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial. Diabetologia. 2018 Jul;61(7):1581-1591. doi: 10.1007/s00125-018-4619-x. Epub 2018 May 4.

  PMID: 29728717 DERIVED

• Alshehry ZH, Mundra PA, Barlow CK, Mellett NA, Wong G, McConville MJ, Simes J, Tonkin AM, Sullivan DR, Barnes EH, Nestel PJ, Kingwell BA, Marre M, Neal B, Poulter NR, Rodgers A, Williams B, Zoungas S, Hillis GS, Chalmers J, Woodward M, Meikle PJ. Plasma Lipidomic Profiles Improve on Traditional Risk Factors for the Prediction of Cardiovascular Events in Type 2 Diabetes Mellitus. Circulation. 2016 Nov 22;134(21):1637-1650. doi: 10.1161/CIRCULATIONAHA.116.023233. Epub 2016 Oct 18.

  PMID: 27756783 DERIVED

• Mohammedi K, Woodward M, Zoungas S, Li Q, Harrap S, Patel A, Marre M, Chalmers J; ADVANCE Collaborative Group. Absence of Peripheral Pulses and Risk of Major Vascular Outcomes in Patients With Type 2 Diabetes. Diabetes Care. 2016 Dec;39(12):2270-2277. doi: 10.2337/dc16-1594. Epub 2016 Sep 27.

  PMID: 27679583 DERIVED

• van der Leeuw J, Visseren FL, Woodward M, van der Graaf Y, Grobbee DE, Harrap S, Heller S, Mancia G, Marre M, Poulter N, Zoungas S, Chalmers J. Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes. Diabetologia. 2016 Dec;59(12):2603-2612. doi: 10.1007/s00125-016-4082-5. Epub 2016 Sep 1.

  PMID: 27586250 DERIVED

• Mohammedi K, Woodward M, Hirakawa Y, Zoungas S, Williams B, Lisheng L, Rodgers A, Mancia G, Neal B, Harrap S, Marre M, Chalmers J; ADVANCE Collaborative Group. Microvascular and Macrovascular Disease and Risk for Major Peripheral Arterial Disease in Patients With Type 2 Diabetes. Diabetes Care. 2016 Oct;39(10):1796-803. doi: 10.2337/dc16-0588. Epub 2016 Jul 25.

  PMID: 27456835 DERIVED

• Hayes A, Arima H, Woodward M, Chalmers J, Poulter N, Hamet P, Clarke P. Changes in Quality of Life Associated with Complications of Diabetes: Results from the ADVANCE Study. Value Health. 2016 Jan;19(1):36-41. doi: 10.1016/j.jval.2015.10.010. Epub 2015 Dec 2.

  PMID: 26797234 DERIVED

• Blomster JI, Woodward M, Zoungas S, Hillis GS, Harrap S, Neal B, Poulter N, Mancia G, Chalmers J, Huxley R. The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: an observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. BMJ Open. 2016 Jan 8;6(1):e009668. doi: 10.1136/bmjopen-2015-009668.

  PMID: 26747037 DERIVED

• Thomas MC, Woodward M, Neal B, Li Q, Pickering R, Marre M, Williams B, Perkovic V, Cooper ME, Zoungas S, Chalmers J, Hillis GS; ADVANCE Collaborative Group. Relationship between levels of advanced glycation end products and their soluble receptor and adverse outcomes in adults with type 2 diabetes. Diabetes Care. 2015 Oct;38(10):1891-7. doi: 10.2337/dc15-0925. Epub 2015 Aug 7.

  PMID: 26253728 DERIVED

• van der Leeuw J, Visseren FL, Woodward M, Zoungas S, Kengne AP, van der Graaf Y, Glasziou P, Hamet P, MacMahon S, Poulter N, Grobbee DE, Chalmers J. Predicting the effects of blood pressure-lowering treatment on major cardiovascular events for individual patients with type 2 diabetes mellitus: results from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation. Hypertension. 2015 Jan;65(1):115-21. doi: 10.1161/HYPERTENSIONAHA.114.04421. Epub 2014 Oct 13.

  PMID: 25312436 DERIVED

• Welsh P, Woodward M, Hillis GS, Li Q, Marre M, Williams B, Poulter N, Ryan L, Harrap S, Patel A, Chalmers J, Sattar N. Do cardiac biomarkers NT-proBNP and hsTnT predict microvascular events in patients with type 2 diabetes? Results from the ADVANCE trial. Diabetes Care. 2014 Aug;37(8):2202-10. doi: 10.2337/dc13-2625. Epub 2014 May 30.

  PMID: 24879844 DERIVED

• Hirakawa Y, Arima H, Zoungas S, Ninomiya T, Cooper M, Hamet P, Mancia G, Poulter N, Harrap S, Woodward M, Chalmers J. Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care. 2014 Aug;37(8):2359-65. doi: 10.2337/dc14-0199. Epub 2014 May 8.

  PMID: 24812434 DERIVED

• Lowe G, Woodward M, Hillis G, Rumley A, Li Q, Harrap S, Marre M, Hamet P, Patel A, Poulter N, Chalmers J. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes. 2014 Mar;63(3):1115-23. doi: 10.2337/db12-1625. Epub 2013 Nov 12.

  PMID: 24222348 DERIVED

• Hata J, Arima H, Rothwell PM, Woodward M, Zoungas S, Anderson C, Patel A, Neal B, Glasziou P, Hamet P, Mancia G, Poulter N, Williams B, Macmahon S, Chalmers J; ADVANCE Collaborative Group. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation. 2013 Sep 17;128(12):1325-34. doi: 10.1161/CIRCULATIONAHA.113.002717. Epub 2013 Aug 7.

  PMID: 23926207 DERIVED

• Blomster JI, Chow CK, Zoungas S, Woodward M, Patel A, Poulter NR, Marre M, Harrap S, Chalmers J, Hillis GS. The influence of physical activity on vascular complications and mortality in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Nov;15(11):1008-12. doi: 10.1111/dom.12122. Epub 2013 Jun 11.

  PMID: 23675676 DERIVED

• Zaman MJ, Patel A, Chalmers J, Woodward M, Clarke P, Li Q, Zoungas S. The effects of patient characteristics and geographical region on hospitalization in patients with type 2 diabetes. Diabet Med. 2013 Aug;30(8):918-25. doi: 10.1111/dme.12181. Epub 2013 Apr 12.

  PMID: 23534416 DERIVED

• Hata J, Arima H, Zoungas S, Fulcher G, Pollock C, Adams M, Watson J, Joshi R, Kengne AP, Ninomiya T, Anderson C, Woodward M, Patel A, Mancia G, Poulter N, MacMahon S, Chalmers J, Neal B; ADVANCE Collaborative Group. Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial. PLoS One. 2013;8(2):e55807. doi: 10.1371/journal.pone.0055807. Epub 2013 Feb 4.

  PMID: 23390553 DERIVED

• Hillis GS, Hata J, Woodward M, Perkovic V, Arima H, Chow CK, Zoungas S, Patel A, Poulter NR, Mancia G, Williams B, Chalmers J. Resting heart rate and the risk of microvascular complications in patients with type 2 diabetes mellitus. J Am Heart Assoc. 2012 Oct;1(5):e002832. doi: 10.1161/JAHA.112.002832. Epub 2012 Oct 25.

  PMID: 23316296 DERIVED

• Morton J, Zoungas S, Li Q, Patel AA, Chalmers J, Woodward M, Celermajer DS, Beulens JW, Stolk RP, Glasziou P, Ng MK; ADVANCE Collaborative Group. Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study. Diabetes Care. 2012 Nov;35(11):2201-6. doi: 10.2337/dc12-0306. Epub 2012 Aug 13.

  PMID: 22891258 DERIVED

• Wong G, Zoungas S, Lo S, Chalmers J, Cass A, Neal B, Woodward M, Perkovic V, Glasziou P, Williams B, Howard K, Chapman JR, Craig JC. The risk of cancer in people with diabetes and chronic kidney disease. Nephrol Dial Transplant. 2012 Aug;27(8):3337-44. doi: 10.1093/ndt/gfs022. Epub 2012 Feb 21.

  PMID: 22357699 DERIVED

• Zoungas S, Chalmers J, Ninomiya T, Li Q, Cooper ME, Colagiuri S, Fulcher G, de Galan BE, Harrap S, Hamet P, Heller S, MacMahon S, Marre M, Poulter N, Travert F, Patel A, Neal B, Woodward M; ADVANCE Collaborative Group. Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia. 2012 Mar;55(3):636-43. doi: 10.1007/s00125-011-2404-1. Epub 2011 Dec 21.

  PMID: 22186981 DERIVED

• Woodward M, Patel A, Zoungas S, Liu L, Pan C, Poulter N, Januszewicz A, Tandon N, Joshi P, Heller S, Neal B, Chalmers J. Does glycemic control offer similar benefits among patients with diabetes in different regions of the world? Results from the ADVANCE trial. Diabetes Care. 2011 Dec;34(12):2491-5. doi: 10.2337/dc11-0755. Epub 2011 Oct 4.

  PMID: 21972410 DERIVED

• Stefansdottir G, Zoungas S, Chalmers J, Kengne AP, Knol MJ, Leufkens HG, Patel A, Woodward M, Grobbee DE, De Bruin ML. Intensive glucose control and risk of cancer in patients with type 2 diabetes. Diabetologia. 2011 Jul;54(7):1608-14. doi: 10.1007/s00125-011-2104-x. Epub 2011 Apr 21.

  PMID: 21509444 DERIVED

• Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M, Heller S; ADVANCE Collaborative Group. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010 Oct 7;363(15):1410-8. doi: 10.1056/NEJMoa1003795.

  PMID: 20925543 DERIVED

• Glasziou PP, Clarke P, Alexander J, Rajmokan M, Beller E, Woodward M, Chalmers J, Poulter N, Patel A. Cost-effectiveness of lowering blood pressure with a fixed combination of perindopril and indapamide in type 2 diabetes mellitus: an ADVANCE trial-based analysis. Med J Aust. 2010 Sep 20;193(6):320-4. doi: 10.5694/j.1326-5377.2010.tb03941.x.

  PMID: 20854235 DERIVED

• Ninomiya T, Zoungas S, Neal B, Woodward M, Patel A, Perkovic V, Cass A, Cooper M, Grobbee D, Hamet P, Harrap S, Liu L, Mancia G, Mogensen CE, Poulter N, Rodgers A, Williams B, MacMahon S, Chalmers J; ADVANCE Collaborative Group. Efficacy and safety of routine blood pressure lowering in older patients with diabetes: results from the ADVANCE trial. J Hypertens. 2010 Jun;28(6):1141-9.

  PMID: 20486273 DERIVED

• Chalmers J, Arima H. Importance of blood pressure lowering in type 2 diabetes: focus on ADVANCE. J Cardiovasc Pharmacol. 2010 Apr;55(4):340-7. doi: 10.1097/fjc.0b013e3181d26469.

  PMID: 20422738 DERIVED

• Meier M, Hummel M. Cardiovascular disease and intensive glucose control in type 2 diabetes mellitus: moving practice toward evidence-based strategies. Vasc Health Risk Manag. 2009;5:859-71. doi: 10.2147/vhrm.s4808. Epub 2009 Nov 2.

  PMID: 19898642 DERIVED

• de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai A, Cooper M, Grobbee DE, Hackett M, Hamet P, Heller SR, Lisheng L, MacMahon S, Mancia G, Neal B, Pan CY, Patel A, Poulter N, Travert F, Woodward M; ADVANCE Collaborative group. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia. 2009 Nov;52(11):2328-2336. doi: 10.1007/s00125-009-1484-7. Epub 2009 Aug 18.

  PMID: 19688336 DERIVED

• Zoungas S, de Galan BE, Ninomiya T, Grobbee D, Hamet P, Heller S, MacMahon S, Marre M, Neal B, Patel A, Woodward M, Chalmers J; ADVANCE Collaborative Group; Cass A, Glasziou P, Harrap S, Lisheng L, Mancia G, Pillai A, Poulter N, Perkovic V, Travert F. Combined effects of routine blood pressure lowering and intensive glucose control on macrovascular and microvascular outcomes in patients with type 2 diabetes: New results from the ADVANCE trial. Diabetes Care. 2009 Nov;32(11):2068-74. doi: 10.2337/dc09-0959. Epub 2009 Aug 3.

  PMID: 19651921 DERIVED

• Beulens JW, Patel A, Vingerling JR, Cruickshank JK, Hughes AD, Stanton A, Lu J, McG Thom SA, Grobbee DE, Stolk RP; AdRem project team; ADVANCE management committee. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia. 2009 Oct;52(10):2027-36. doi: 10.1007/s00125-009-1457-x. Epub 2009 Jul 25.

  PMID: 19633827 DERIVED

• de Galan BE, Perkovic V, Ninomiya T, Pillai A, Patel A, Cass A, Neal B, Poulter N, Harrap S, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Glasziou P, Grobbee DE, MacMahon S, Chalmers J; ADVANCE Collaborative Group. Lowering blood pressure reduces renal events in type 2 diabetes. J Am Soc Nephrol. 2009 Apr;20(4):883-92. doi: 10.1681/ASN.2008070667. Epub 2009 Feb 18.

  PMID: 19225038 DERIVED

• ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560-72. doi: 10.1056/NEJMoa0802987. Epub 2008 Jun 6.

  PMID: 18539916 DERIVED

• Patel A; ADVANCE Collaborative Group; MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007 Sep 8;370(9590):829-40. doi: 10.1016/S0140-6736(07)61303-8.

  PMID: 17765963 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Stroke

Interventions

indapamide, perindopril drug combination

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• John Chalmers, MB BS PhD

  The George Institute

  PRINCIPAL INVESTIGATOR

• Stephen W MacMahon, BSc PhD MPH

  The George Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 5, 2005
• Study Start: June 1, 2001
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: April 11, 2025

Record last verified: 2008-09

Locations

NL (1); GB (1); AU (1); CA (1); CN (1)