Action to Control Cardiovascular Risk in Diabetes (ACCORD)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Robert P. Byington, Wake Forest School of Medicine
ClinicalTrials.gov Identifier:
NCT00000620
First received: October 27, 1999
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Atherosclerosis
Cardiovascular Diseases
Hypercholesterolemia
Hypertension
Diabetes Mellitus, Type 2
Diabetes Mellitus
Coronary Disease
Drug: Anti-hyperglycemic Agents
Drug: Anti-hypertensive Agents
Drug: Blinded fenofibrate or placebo plus simvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Action to Control Cardiovascular Risk in Diabetes (ACCORD)

Resource links provided by NLM:


Further study details as provided by Wake Forest School of Medicine:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.


Secondary Outcome Measures:
  • Death From Any Cause in the Glycemia Trial. [ Time Frame: 4.9 years ] [ Designated as safety issue: Yes ]

    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).


  • Stroke in the Blood Pressure Trial. [ Time Frame: 4.7 years ] [ Designated as safety issue: Yes ]
    Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial.

  • First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial. [ Time Frame: 4.7 years ] [ Designated as safety issue: Yes ]
    Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants.


Enrollment: 10251
Study Start Date: September 1999
Study Completion Date: December 2012
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glycemia Trial: intensive control
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%.
Drug: Anti-hyperglycemic Agents
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%).
Other Names:
  • glimepiride (Amaryl)
  • metformin (Glucophage)
  • repaglinide (Gluconorm, Prandin)
  • rosiglitazone (Avandia)
  • pioglitazone (Actos)
  • human regular insulin (Novolin ge Toronto)
  • human NPH (Novolin N)
  • human mixed (Novolin 70/30)
  • human isophane (Novolin ge NPH)
  • human 30/70 (Novolin ge 30/70)
  • insulin aspart (NovoRapid, NovoLog)
  • insulin detemir (Levemir)
  • human regular insulin (Novolin R)
  • insulin glargine (Lantus)
  • Acarbose
Active Comparator: Glycemia Trial: standard control
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%.
Drug: Anti-hyperglycemic Agents
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%).
Other Names:
  • glimepiride (Amaryl)
  • metformin (Glucophage)
  • repaglinide (Gluconorm, Prandin)
  • rosiglitazone (Avandia)
  • pioglitazone (Actos)
  • human regular insulin (Novolin ge Toronto)
  • human NPH (Novolin N)
  • human mixed (Novolin 70/30)
  • human isophane (Novolin ge NPH)
  • human 30/70 (Novolin ge 30/70)
  • insulin aspart (NovoRapid, NovoLog)
  • insulin detemir (Levemir)
  • human regular insulin (Novolin R)
  • insulin glargine (Lantus)
  • Acarbose
Experimental: BP Trial: intensive control
Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg.
Drug: Anti-hypertensive Agents
Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).
Other Names:
  • benazepril (Lotensin, Zestril, Altace)
  • chlorthalidone (Thalitone)
  • metoprolol (Toprol XL)
  • diltiazem (Tiazac)
  • plendil (Felodipine)
  • terazosin (Hytrin)
  • candesartan (Atacand)
  • valsartan (Diovan)
  • furosemide
  • reserpine
  • hydralazine
  • carvedilol (Coreg)
  • triamterene / hydrochlorothiazide (Dyazide)
  • metoprolol / hydrochlorothiazide(Lopressor HCT)
  • benazepril / hydrochlorothiazide (Lotensin HCT)
  • lisinopril / hydrochlorothiazide (Zestoretic)
  • candesartan / hydrochlorothiazide (Atacand HCT)
  • valsartan / hydrochlorothiazide (Diovan HCT)
  • amlodipine / benazepril (Lotrel)
Active Comparator: BP Trial: standard control
Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg.
Drug: Anti-hypertensive Agents
Multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).
Other Names:
  • benazepril (Lotensin, Zestril, Altace)
  • chlorthalidone (Thalitone)
  • metoprolol (Toprol XL)
  • diltiazem (Tiazac)
  • plendil (Felodipine)
  • terazosin (Hytrin)
  • candesartan (Atacand)
  • valsartan (Diovan)
  • furosemide
  • reserpine
  • hydralazine
  • carvedilol (Coreg)
  • triamterene / hydrochlorothiazide (Dyazide)
  • metoprolol / hydrochlorothiazide(Lopressor HCT)
  • benazepril / hydrochlorothiazide (Lotensin HCT)
  • lisinopril / hydrochlorothiazide (Zestoretic)
  • candesartan / hydrochlorothiazide (Atacand HCT)
  • valsartan / hydrochlorothiazide (Diovan HCT)
  • amlodipine / benazepril (Lotrel)
Experimental: Lipid Trial: fenofibrate
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.
Drug: Blinded fenofibrate or placebo plus simvastatin
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.
Other Name: fenofibrate (Tricor)
Placebo Comparator: Lipid Trial: placebo
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.
Drug: Blinded fenofibrate or placebo plus simvastatin
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.
Other Name: fenofibrate (Tricor)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000620

Locations
United States, Minnesota
Minneapolis Medical Research Foundation
Minneapolis, Minnesota, United States, 55404
United States, New York
Columbia University
New York, New York, United States, 10027
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27106
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Tennessee
Veterans Affairs
Memphis, Tennessee, United States, 38104
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Canada, Ontario
McMaster University
Hamilton, Ontario, Canada
Sponsors and Collaborators
Wake Forest School of Medicine
Investigators
Study Director: Denise Simons-Morton, MD, PhD National Heart, Lung, and Blood Institute (NHLBI)
Study Chair: William Friedewald, MD Columbia University, New York, NY
Principal Investigator: Robert Byington, PhD Wake Forest University, Winston-Salem, NC
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Robert P. Byington, Professor, Wake Forest School of Medicine
ClinicalTrials.gov Identifier: NCT00000620     History of Changes
Other Study ID Numbers: 123, N01HC95178, N01HC95179, N01HC95180, N01HC95181, N01HC95182, N01HC95183, N01HC95184, IAA#Y1HC9035, IAA#Y1HC1010
Study First Received: October 27, 1999
Results First Received: September 5, 2014
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Wake Forest School of Medicine:
Diabetes Mellitus, Non-Insulin-Dependent

Additional relevant MeSH terms:
Hypertension
Diabetes Mellitus
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Diabetes Mellitus, Type 2
Hypercholesterolemia
Coronary Disease
Coronary Artery Disease
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Arterial Occlusive Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Myocardial Ischemia
Heart Diseases
Insulin, Globin Zinc
Pioglitazone
Insulin
Hypoglycemic Agents
Fenofibrate
Simvastatin
Candesartan
Candesartan cilexetil
Valsartan
Benazepril
Metoprolol

ClinicalTrials.gov processed this record on September 30, 2014