AtherosclerosisPhase 3ACCORDNCT00000620
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
A Phase 3 study testing Anti-hyperglycemic Agents and Anti-hypertensive Agents in people with Atherosclerosis and Cardiovascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 7 sites in 2 countries.
Trial summary
The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management. Read more about this study
- Who is it for?
- Ages 40 to 79 years
- Conditions the study is for
- Atherosclerosis, Cardiovascular Diseases, Hypercholesterolemia
- What is being tested?
- Anti-hyperglycemic Agents and Anti-hypertensive Agents
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10,251 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Sep 1999to Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest
- For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina)
- For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors
- HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)
Who cannot join
None listed.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Case Western Reserve University
Cleveland, Ohio, 44106
Veterans Affairs
Memphis, Tennessee, 38104
Minneapolis Medical Research Foundation
Minneapolis, Minnesota, 55404
Columbia University
New York, New York, 10027
University of Washington
Seattle, Washington, 98195
Wake Forest University
Winston-Salem, North Carolina, 27106
About this study
The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
Read the detailed description
BACKGROUND:
Currently, about 17 million Americans have been diagnosed with diabetes and more than 90 percent of them have type 2 diabetes. The number of people with this form of diabetes, formerly known as adult onset or non-insulin dependent diabetes, is growing rapidly. By 2050, the number of Americans with diagnosed diabetes is projected to increase by 165 percent to 29 million, of whom 27 million will have the type 2 form. Cardiovascular disease (CVD) is the leading cause of death in people with type 2 diabetes; these individuals die of CVD at rates two to four times higher than those who do not have diabetes. They also experience more nonfatal heart attacks and strokes.
Type 2 diabetes is associated with older age and is more common in those who are overweight or obese and have a family history of diabetes. Women with a history of diabetes during pregnancy, adults with impaired glucose tolerance, people with a sedentary lifestyle, and members of a minority race/ethnicity are also at a greater risk for developing type 2 diabetes. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Pacific Islanders are at particularly high risk for type 2 diabetes.
DESIGN NARRATIVE:
The three strategies tested in ACCORD included the following: (1) Blood sugar - ACCORD was designed to determine whether lowering blood glucose to a level closer to normal than called for in current guidelines reduces CVD risk. The study estimated effects on CVD of that level compared with a level that is usually targeted. (2) Blood pressure - many people with type 2 diabetes have high blood pressure. The blood pressure part of the trial was designed to determine the effects of lowering blood pressure in the context of good blood sugar control, that is to determine whether lowering blood pressure to normal (systolic pressure less than 120 mm Hg) will better reduce CVD risk, as compared to a usually-targeted level in current clinical practice (i.e., below the definition of hypertension; systolic pressure less than 140 mm Hg). (3) Blood Fats - Many people with diabetes have high levels of LDL ("bad") cholesterol and triglycerides, as well as low levels of HDL ("good") cholesterol. ACCORD participants who are selected for this part of the trial were assigned to an intervention to improve blood fat levels. This part of the study looked at the effects of lowering LDL cholesterol and blood triglycerides and increasing HDL cholesterol compared to an intervention that only lowers LDL cholesterol, all in the context of good blood sugar control. A drug from a class of drugs called "fibrates" was used to lower triglycerides and increase HDL cholesterol, whereas a drug from the class of drugs called "statins" was used to lower LDL cholesterol.
All ACCORD participants received blood sugar treatment from the study. Based on the second trial (Blood Pressure or Lipid) they were assigned to, participants also received their high blood pressure or cholesterol care from the study. Study participants received all medication and treatments related to the study free of charge. Individuals who selected for and consented to participate in the ACCORD study continued to see their personal physician for all other health care.
In summary, the ACCORD Study was a double 2x2 factorial design with factors consisting of: intensive versus standard glycemic control, intensive versus standard blood pressure control, and blinded fenofibrate or placebo in combination with simvastatin to maintain desirable LDL-C levels. All 10,251 participants were randomized to the glycemic interventions; a subgroup of 4,733 participants who met the blood pressure entry criteria were randomized to the blood pressure interventions in one 2x2 trial; and a distinct subgroup of 5,518 participants who met the lipid entry criteria were randomized to the lipid interventions in the second 2x2 trial. All participants had established type 2 diabetes and were recruited from 77 clinical centers in the United States (64 sites) and Canada (13 sites).
On February 6, 2008, the National Heart, Lung and Blood Institute (NHLBI) announced that participants in the intensive glycemia treatment would be transitioned to the ACCORD standard glycemic treatment approach due to higher mortality in the intensive treatment group terminating the experimental arm of the Glycemia Trial early. The Blood Pressure and Lipid trials continued as designed to their planned termination in 2009.
- Conditions
- Atherosclerosis, Cardiovascular Diseases, Hypercholesterolemia, Hypertension, Diabetes Mellitus, Type 2, Diabetes Mellitus
- Being tested
- Anti-hyperglycemic Agents, Anti-hypertensive Agents, Blinded fenofibrate or placebo plus simvastatin
- Keywords
- Diabetes Mellitus, Non-Insulin-Dependent
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases, Hypercholesterolemia, Hypertension, Diabetes Mellitus, Type 2, Diabetes Mellitus, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-hyperglycemic AgentsDrug
Also called glimepiride (Amaryl), metformin (Glucophage), repaglinide (Gluconorm, Prandin), rosiglitazone (Avandia)
Multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals (intensive control <6%; standard control 7.0-7.9%).
Anti-hypertensive AgentsDrug
Also called benazepril (Lotensin, Zestril, Altace), chlorthalidone (Thalitone), metoprolol (Toprol XL), diltiazem (Tiazac)
Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).
Blinded fenofibrate or placebo plus simvastatinDrug
Also called fenofibrate (Tricor)
Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.
| Study group | Role | What they receive |
|---|---|---|
| Glycemia Trial: intensive control | Experimental | Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels <6.0%. Receives: Drug: Anti-hyperglycemic Agents |
| Glycemia Trial: standard control | Active comparator | Open label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 - 7.9%. Receives: Drug: Anti-hyperglycemic Agents |
| BP Trial: intensive control | Experimental | Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. Receives: Drug: Anti-hypertensive Agents |
| BP Trial: standard control | Active comparator | Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg. Receives: Drug: Anti-hypertensive Agents |
| Lipid Trial: fenofibrate | Experimental | Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m2 in combination with open label simvastatin. Receives: Drug: Blinded fenofibrate or placebo plus simvastatin |
| Lipid Trial: placebo | Placebo comparator | Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR <50 mL/min/1.73m2 in combination with open label simvastatin. Receives: Drug: Blinded fenofibrate or placebo plus simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. This was the primary outcome measure in all three trials: Glycemia (all participants), Blood Pressure (subgroup of participants not in Lipid Trial), and Lipid (subgroup of participants not in Blood Pressure Trial).
In the Glycemia Trial, a finding of higher mortality in the intensive arm group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid) to their planned completion.
Measured: 4.9 years
First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial.
Measured: 4.7 years
First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.
Measured: 4.7 years
Secondary outcomes (3)
Death From Any Cause in the Glycemia Trial.
Time to death from any cause. Secondary measure for Glycemia Trial.
A finding of higher mortality in the intensive-therapy group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid).
Measured: 4.9 years
Stroke in the Blood Pressure Trial.
Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial.
Measured: 4.7 years
First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants.
Measured: 4.7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startSep 1999
- Primary completionJun 2009
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (128)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 10,251 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Aging (NIA), National Eye Institute (NEI), Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Denise Simons-Morton, MD, PhD, Study director, National Heart, Lung, and Blood Institute (NHLBI)William Friedewald, MD, Study chair, Columbia UniversityRobert Byington, PhD, Principal investigator, Wake Forest University, Winston-Salem, NC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000620
- Sponsor's protocol ID
- 123
- Other IDs
- N01HC95178, N01HC95179, N01HC95180, N01HC95181, N01HC95182, N01HC95183, N01HC95184, IAA#Y1HC9035
- Acronym
- ACCORD
- Status last verified
- Nov 2014
- First submitted
- 27 Oct 1999
- Last updated
- 22 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cushman WC, Grimm RH Jr, Cutler JA, Evans GW, Capes S, Corson MA, Sadler LS, Alderman MH, Peterson K, Bertoni A, Basile JN; ACCORD Study Group. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):44i-55i. doi: 10.1016/j.amjcard.2007.03.005. Epub 2007 Apr 16.
PubMed 17599425Williamson JD, Miller ME, Bryan RN, Lazar RM, Coker LH, Johnson J, Cukierman T, Horowitz KR, Murray A, Launer LJ; ACCORD Study Group. The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol. 2007 Jun 18;99(12A):112i-122i. doi: 10.1016/j.amjcard.2007.03.029. Epub 2007 Apr 12.
PubMed 17599421Sullivan MD, Anderson RT, Aron D, Atkinson HH, Bastien A, Chen GJ, Feeney P, Gafni A, Hwang W, Katz LA, Narayan KM, Nwachuku C, O'Connor PJ, Zhang P; ACCORD Study Group. Health-related quality of life and cost-effectiveness components of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: rationale and design. Am J Cardiol. 2007 Jun 18;99(12A):90i-102i. doi: 10.1016/j.amjcard.2007.03.027. Epub 2007 Apr 13.
PubMed 17599429Bonds DE, Kurashige EM, Bergenstal R, Brillon D, Domanski M, Felicetta JV, Fonseca VA, Hall K, Hramiak I, Miller ME, Osei K, Simons-Morton DG; ACCORD Study Group. Severe hypoglycemia monitoring and risk management procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):80i-89i. doi: 10.1016/j.amjcard.2007.03.026. Epub 2007 Apr 17.
PubMed 17599428Kingry C, Bastien A, Booth G, Geraci TS, Kirpach BR, Lovato LC, Margolis KL, Rosenberg Y, Sperl-Hillen JM, Vargo L, Williamson JD, Probstfield JL; ACCORD Study Group. Recruitment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):68i-79i. doi: 10.1016/j.amjcard.2007.03.025. Epub 2007 Apr 12.
PubMed 17599427Ginsberg HN, Bonds DE, Lovato LC, Crouse JR, Elam MB, Linz PE, O'connor PJ, Leiter LA, Weiss D, Lipkin E, Fleg JL; ACCORD Study Group. Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):56i-67i. doi: 10.1016/j.amjcard.2007.03.024. Epub 2007 Apr 12.
PubMed 17599426Goff DC Jr, Gerstein HC, Ginsberg HN, Cushman WC, Margolis KL, Byington RP, Buse JB, Genuth S, Probstfield JL, Simons-Morton DG; ACCORD Study Group. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):4i-20i. doi: 10.1016/j.amjcard.2007.03.002. Epub 2007 Apr 12.
PubMed 17599424Gerstein HC, Riddle MC, Kendall DM, Cohen RM, Goland R, Feinglos MN, Kirk JK, Hamilton BP, Ismail-Beigi F, Feeney P; ACCORD Study Group. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):34i-43i. doi: 10.1016/j.amjcard.2007.03.004. Epub 2007 Apr 19.
PubMed 17599423ACCORD Study Group; Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007 Jun 18;99(12A):21i-33i. doi: 10.1016/j.amjcard.2007.03.003. Epub 2007 Apr 16.
PubMed 17599422Chew EY, Ambrosius WT, Howard LT, Greven CM, Johnson S, Danis RP, Davis MD, Genuth S, Domanski M; ACCORD Study Group. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am J Cardiol. 2007 Jun 18;99(12A):103i-111i. doi: 10.1016/j.amjcard.2007.03.028. Epub 2007 Apr 13.
PubMed 17599420Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.
PubMed 18539917Meng X, Wang Y, Xiang Y, Xu X, Zhang X, Wang S, Tan Z, Zhao X, Wang K, Li M, Wang T, Zhao Z, Lu J, Xu M, Zheng J, Wang W, Ning G, Bi Y, Xu Y. Effects of intensive blood pressure control on cardio-kidney outcomes by KDIGO risk categories: a Post Hoc analysis of ACCORD-BP and SPRINT trials. Hypertens Res. 2026 Sep 3. doi: 10.1038/s41440-026-02792-5. Online ahead of print.
PubMed 42693262Breeyear JH, House JS, Kvale M, Nam S, Akhtari FS, Shah HS, Hedderson MM, Giacomini KM, Mychaleckyj JC, Doria A, Wagner MJ, Li JH, Yee SW, Buse JB, Woychik RP, Rotroff DM, Motsinger-Reif AA. Disentangling Sex Differences in Sulfonylurea Drug Response With Genome-Wide Association Studies in Individuals With Type 2 Diabetes. Clin Pharmacol Ther. 2026 Oct;120(4):1004-1015. doi: 10.1002/cpt.70381. Epub 2026 Jul 27.
PubMed 42504935Chlebek C, Bussberg V, Narain NR, Kiebish MA, Tseng YH, Rosen CJ, Lynes MD. Baseline serum metabolites predict fractures in individuals who were Black and had type 2 diabetes. Front Endocrinol (Lausanne). 2026 Jun 2;17:1777636. doi: 10.3389/fendo.2026.1777636. eCollection 2026.
PubMed 42312207Liu Y, Lyu Y, Liu Y, Zhang J, Song Z, Chen K, Jiang Z, Yan H, Chen T, Li C. Individual participant-level analysis of four randomized clinical trials examined therapeutic effects of blood pressure lowering on hierarchical kidney outcome using win statistics. Kidney Int. 2026 Jul;110(1):178-189. doi: 10.1016/j.kint.2026.02.032. Epub 2026 Mar 26.
PubMed 41903707
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Action to Control Cardiovascular Risk in Diabetes (ACCORD)
- ClinicalTrials.gov ID
- NCT00000620
- Acronym / sponsor ID
- ACCORD / 123
- Conditions
- Atherosclerosis, Cardiovascular Diseases, Hypercholesterolemia, Hypertension, Diabetes Mellitus, Type 2, Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Non-Insulin-Dependent
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10,251 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Aging (NIA), National Eye Institute (NEI), Centers for Disease Control and Prevention
- Study start
- Sep 1999
- Primary completion
- Jun 2009 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 28 Oct 1999 (estimated)
- Results
- Posted 15 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to prevent major cardiovascular events (heart attack, stroke, or cardiovascular death) in adults with type 2 diabetes mellitus using intensive glycemic control, intensive blood pressure control, and multiple lipid management.
Detailed description
BACKGROUND:
Currently, about 17 million Americans have been diagnosed with diabetes and more than 90 percent of them have type 2 diabetes. The number of people with this form of diabetes, formerly known as adult onset or non-insulin dependent diabetes, is growing rapidly. By 2050, the number of Americans with diagnosed diabetes is projected to increase by 165 percent to 29 million, of whom 27 million will have the type 2 form. Cardiovascular disease (CVD) is the leading cause of death in people with type 2 diabetes; these individuals die of CVD at rates two to four times higher than those who do not have diabetes. They also experience more nonfatal heart attacks and strokes.
Type 2 diabetes is associated with older age and is more common in those who are overweight or obese and have a family history of diabetes. Women with a history of diabetes during pregnancy, adults with impaired glucose tolerance, people with a sedentary lifestyle, and members of a minority race/ethnicity are also at a greater risk for developing type 2 diabetes. African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans and Pacific Islanders are at particularly high risk for type 2 diabetes.
DESIGN NARRATIVE:
The three strategies tested in ACCORD included the following: (1) Blood sugar - ACCORD was designed to determine whether lowering blood glucose to a level closer to normal than called for in current guidelines reduces CVD risk. The study estimated effects on CVD of that level compared with a level that is usually targeted. (2) Blood pressure - many people with type 2 diabetes have high blood pressure. The blood pressure part of the trial was designed to determine the effects of lowering blood pressure in the context of good blood sugar control, that is to determine whether lowering blood pressure to normal (systolic pressure less than 120 mm Hg) will better reduce CVD risk, as compared to a usually-targeted level in current clinical practice (i.e., below the definition of hypertension; systolic pressure less than 140 mm Hg). (3) Blood Fats - Many people with diabetes have high levels of LDL ("bad") cholesterol and triglycerides, as well as low levels of HDL ("good") cholesterol. ACCORD participants who are selected for this part of the trial were assigned to an intervention to improve blood fat levels. This part of the study looked at the effects of lowering LDL cholesterol and blood triglycerides and increasing HDL cholesterol compared to an intervention that only lowers LDL cholesterol, all in the context of good blood sugar control. A drug from a class of drugs called "fibrates" was used to lower triglycerides and increase HDL cholesterol, whereas a drug from the class of drugs called "statins" was used to lower LDL cholesterol.
All ACCORD participants received blood sugar treatment from the study. Based on the second trial (Blood Pressure or Lipid) they were assigned to, participants also received their high blood pressure or cholesterol care from the study. Study participants received all medication and treatments related to the study free of charge. Individuals who selected for and consented to participate in the ACCORD study continued to see their personal physician for all other health care.
In summary, the ACCORD Study was a double 2x2 factorial design with factors consisting of: intensive versus standard glycemic control, intensive versus standard blood pressure control, and blinded fenofibrate or placebo in combination with simvastatin to maintain desirable LDL-C levels. All 10,251 participants were randomized to the glycemic interventions; a subgroup of 4,733 participants who met the blood pressure entry criteria were randomized to the blood pressure interventions in one 2x2 trial; and a distinct subgroup of 5,518 participants who met the lipid entry criteria were randomized to the lipid interventions in the second 2x2 trial. All participants had established type 2 diabetes and were recruited from 77 clinical centers in the United States (64 sites) and Canada (13 sites).
On February 6, 2008, the National Heart, Lung and Blood Institute (NHLBI) announced that participants in the intensive glycemia treatment would be transitioned to the ACCORD standard glycemic treatment approach due to higher mortality in the intensive treatment group terminating the experimental arm of the Glycemia Trial early. The Blood Pressure and Lipid trials continued as designed to their planned termination in 2009.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Glycemia Trial: intensive control | Experimental | Drug: Anti-hyperglycemic AgentsOpen label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels <6.0%. |
| Glycemia Trial: standard control | Active comparator | Drug: Anti-hyperglycemic AgentsOpen label administration of oral anti-hyperglycemic agents and/or insulin in combination with dietary/lifestyle advice as needed to achieve glycated hemoglobin (HbA1c) levels of 7.0 - 7.9%. |
| BP Trial: intensive control | Experimental | Drug: Anti-hypertensive AgentsOpen label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. |
| BP Trial: standard control | Active comparator | Drug: Anti-hypertensive AgentsOpen label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg. |
| Lipid Trial: fenofibrate | Experimental | Drug: Blinded fenofibrate or placebo plus simvastatinDouble blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m2 in combination with open label simvastatin. |
| Lipid Trial: placebo | Placebo comparator | Drug: Blinded fenofibrate or placebo plus simvastatinDouble blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m2 or 54 mg/day in participants with eGFR <50 mL/min/1.73m2 in combination with open label simvastatin. |
Who may qualify
- Ages
- 40 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest
- For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina)
- For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors
- HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-hyperglycemic AgentsAlso: glimepiride (Amaryl), metformin (Glucophage), repaglinide (Gluconorm, Prandin), rosiglitazone (Avandia)Multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals (intensive control <6%; standard control 7.0-7.9%). | Drug | Glycemia Trial: intensive control, Glycemia Trial: standard control |
| Anti-hypertensive AgentsAlso: benazepril (Lotensin, Zestril, Altace), chlorthalidone (Thalitone), metoprolol (Toprol XL), diltiazem (Tiazac)Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg). | Drug | BP Trial: intensive control, BP Trial: standard control |
| Blinded fenofibrate or placebo plus simvastatinAlso: fenofibrate (Tricor)Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day. | Drug | Lipid Trial: fenofibrate, Lipid Trial: placebo |
Primary outcome
First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.
Time frame: 4.9 years
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. This was the primary outcome measure in all three trials: Glycemia (all participants), Blood Pressure (subgroup of participants not in Lipid Trial), and Lipid (subgroup of participants not in Blood Pressure Trial). In the Glycemia Trial, a finding of higher mortality in the intensive arm group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid) to their planned completion.
First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.
Time frame: 4.7 years
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial.
First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.
Time frame: 4.7 years
Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.
3 secondary outcomes
Death From Any Cause in the Glycemia Trial.
Time frame: 4.9 years
Stroke in the Blood Pressure Trial.
Time frame: 4.7 years
First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.
Time frame: 4.7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17599425Cushman WC, Grimm RH Jr, Cutler JA, Evans GW, Capes S, Corson MA, Sadler LS, Alderman MH, Peterson K, Bertoni A, Basile JN; ACCORD Study Group. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):44i-55i. doi: 10.1016/j.amjcard.2007.03.005. Epub 2007 Apr 16.
- Background: PubMed 17599421Williamson JD, Miller ME, Bryan RN, Lazar RM, Coker LH, Johnson J, Cukierman T, Horowitz KR, Murray A, Launer LJ; ACCORD Study Group. The Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes Study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol. 2007 Jun 18;99(12A):112i-122i. doi: 10.1016/j.amjcard.2007.03.029. Epub 2007 Apr 12.
- Background: PubMed 17599429Sullivan MD, Anderson RT, Aron D, Atkinson HH, Bastien A, Chen GJ, Feeney P, Gafni A, Hwang W, Katz LA, Narayan KM, Nwachuku C, O'Connor PJ, Zhang P; ACCORD Study Group. Health-related quality of life and cost-effectiveness components of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: rationale and design. Am J Cardiol. 2007 Jun 18;99(12A):90i-102i. doi: 10.1016/j.amjcard.2007.03.027. Epub 2007 Apr 13.
- Background: PubMed 17599428Bonds DE, Kurashige EM, Bergenstal R, Brillon D, Domanski M, Felicetta JV, Fonseca VA, Hall K, Hramiak I, Miller ME, Osei K, Simons-Morton DG; ACCORD Study Group. Severe hypoglycemia monitoring and risk management procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):80i-89i. doi: 10.1016/j.amjcard.2007.03.026. Epub 2007 Apr 17.
- Background: PubMed 17599427Kingry C, Bastien A, Booth G, Geraci TS, Kirpach BR, Lovato LC, Margolis KL, Rosenberg Y, Sperl-Hillen JM, Vargo L, Williamson JD, Probstfield JL; ACCORD Study Group. Recruitment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):68i-79i. doi: 10.1016/j.amjcard.2007.03.025. Epub 2007 Apr 12.
- Background: PubMed 17599426Ginsberg HN, Bonds DE, Lovato LC, Crouse JR, Elam MB, Linz PE, O'connor PJ, Leiter LA, Weiss D, Lipkin E, Fleg JL; ACCORD Study Group. Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):56i-67i. doi: 10.1016/j.amjcard.2007.03.024. Epub 2007 Apr 12.
- Background: PubMed 17599424Goff DC Jr, Gerstein HC, Ginsberg HN, Cushman WC, Margolis KL, Byington RP, Buse JB, Genuth S, Probstfield JL, Simons-Morton DG; ACCORD Study Group. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):4i-20i. doi: 10.1016/j.amjcard.2007.03.002. Epub 2007 Apr 12.
- Background: PubMed 17599423Gerstein HC, Riddle MC, Kendall DM, Cohen RM, Goland R, Feinglos MN, Kirk JK, Hamilton BP, Ismail-Beigi F, Feeney P; ACCORD Study Group. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007 Jun 18;99(12A):34i-43i. doi: 10.1016/j.amjcard.2007.03.004. Epub 2007 Apr 19.
- Background: PubMed 17599422ACCORD Study Group; Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC Jr, Grimm RH Jr, Margolis KL, Probstfield JL, Simons-Morton DG, Sullivan MD. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007 Jun 18;99(12A):21i-33i. doi: 10.1016/j.amjcard.2007.03.003. Epub 2007 Apr 16.
- Background: PubMed 17599420Chew EY, Ambrosius WT, Howard LT, Greven CM, Johnson S, Danis RP, Davis MD, Genuth S, Domanski M; ACCORD Study Group. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am J Cardiol. 2007 Jun 18;99(12A):103i-111i. doi: 10.1016/j.amjcard.2007.03.028. Epub 2007 Apr 13.
- Results publication: PubMed 18539917Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. doi: 10.1056/NEJMoa0802743. Epub 2008 Jun 6.
- Derived from this study: PubMed 42693262Meng X, Wang Y, Xiang Y, Xu X, Zhang X, Wang S, Tan Z, Zhao X, Wang K, Li M, Wang T, Zhao Z, Lu J, Xu M, Zheng J, Wang W, Ning G, Bi Y, Xu Y. Effects of intensive blood pressure control on cardio-kidney outcomes by KDIGO risk categories: a Post Hoc analysis of ACCORD-BP and SPRINT trials. Hypertens Res. 2026 Sep 3. doi: 10.1038/s41440-026-02792-5. Online ahead of print.
- Click here for the ACCORD trial web siteLink provided by the sponsor.
Related trials for Atherosclerosis
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denise Simons-Morton, MD, PhD study director
National Heart, Lung, and Blood Institute (NHLBI)
William Friedewald, MD study chair
Columbia University
Robert Byington, PhD principal investigator
Wake Forest University, Winston-Salem, NC
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anti-hyperglycemic Agents and Anti-hypertensive Agents in people with Atherosclerosis and Cardiovascular Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial. (time frame: 4.9 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000620, which also lists 128 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.