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Action to Control Cardiovascular Risk in Diabetes (ACCORD) (ACCORD)

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ClinicalTrials.gov Identifier: NCT00000620
Recruitment Status : Completed
First Posted : October 28, 1999
Results First Posted : September 15, 2014
Last Update Posted : November 22, 2016
Sponsor:
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
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Atherosclerosis
Cardiovascular Diseases
Hypercholesterolemia
Hypertension
Diabetes Mellitus, Type 2
Diabetes Mellitus
Coronary Disease
Interventions Drug: Anti-hyperglycemic Agents
Drug: Anti-hypertensive Agents
Drug: Blinded fenofibrate or placebo plus simvastatin
Enrollment 10251
Recruitment Details All participants had established type 2 diabetes and were recruited from 77 clinical centers in the United States (64 sites) and Canada (13 sites). Recruitment occurred in two phases, from January to June 2001 and from February 2003 to October 2005.
Pre-assignment Details Eligible participants provided evidence of ability to routinely monitor capillary blood sugars from written records or electronic downloads from a self-monitoring blood glucose device (SMBG), or (in cases where such records could not be provided) underwent a 2 to 4-week pre-randomization run-in period to evaluate compliance with SMBG monitoring.
Arm/Group Title Glycemia Trial: Intensive Control/BP Trial: Intensive Control Glycemia Trial: Intensive Control/BP Trial: Standard Control Glycemia Trial: Intensive Control/Lipid Trial: Fenofibrate Glycemia Trial: Intensive Control/Lipid Trial: Placebo Glycemia Trial: Standard Control/BP Trial: Intensive Control Glycemia Trial: Standard Control/BP Trial: Standard Control Glycemia Trial: Standard Control/Lipid Trial: Fenofibrate Glycemia Trial: Standard Control/Lipid Trial: Placebo
Hide Arm/Group Description

Glycemia Trial - 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.

Glycemia Trial - 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.

Glycemia Trial - 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.

Glycemia Trial - 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

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/1.73m^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.

Glycemia Trial - 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

BP Trial - Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.

Glycemia Trial - 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

BP Trial - Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals (intensive control <120 mm Hg; standard control <140 mm Hg).

Glycemia Trial - 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

Lipid Trial - Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.

Glycemia Trial - 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.

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/1.73m^2 in combination with open label simvastatin. Blinded fenofibrate or placebo plus simvastatin includes double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2 or matching placebo in combination with open label simvastatin 20 - 40 mg/day.

Period Title: Overall Study
Started 1178 1193 1374 1383 1184 1178 1391 1370
Completed 1016 1057 1204 1205 1049 1026 1242 1224
Not Completed 162 136 170 178 135 152 149 146
Reason Not Completed
Death             86             67             112             126             64             77             91             95
Lost to Follow-up             14             14             14             14             15             15             13             14
Withdrawal by Subject             40             27             28             27             30             32             32             21
missed closeout visit             22             28             16             11             26             28             13             16
Arm/Group Title Glycemia Trial: Intensive Control Glycemia Trial: Standard Control Total
Hide Arm/Group Description 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. Total of all reporting groups
Overall Number of Baseline Participants 5128 5123 10251
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5128 participants 5123 participants 10251 participants
62.2  (6.8) 62.2  (6.8) 62.2  (6.8)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5128 participants 5123 participants 10251 participants
Female
1983
  38.7%
1969
  38.4%
3952
  38.6%
Male
3145
  61.3%
3154
  61.6%
6299
  61.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5128 participants 5123 participants 10251 participants
Hispanic or Latino
358
   7.0%
379
   7.4%
737
   7.2%
Not Hispanic or Latino
4770
  93.0%
4744
  92.6%
9514
  92.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5128 participants 5123 participants 10251 participants
Nonwhite 1828 1819 3647
White 3300 3304 6604
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5128 participants 5123 participants 10251 participants
United States 4376 4367 8743
Canada 752 756 1508
Previous cardiovascular disease (CVD) event  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5128 participants 5123 participants 10251 participants
History of CVD event 1827 1782 3609
No history of CVD event 3301 3341 6642
Glycated hemoglobin  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 5128 participants 5123 participants 10251 participants
8.3  (1.1) 8.3  (1.1) 8.3  (1.1)
Blood pressure  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 5128 participants 5123 participants 10251 participants
Systolic 136.2  (17.0) 136.5  (17.2) 136.4  (17.1)
Diastolic 74.8  (10.6) 75.0  (10.7) 74.9  (10.7)
Cholesterol  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 5128 participants 5123 participants 10251 participants
LDL 104.9  (34.0) 104.9  (33.8) 104.9  (33.9)
HDL 41.8  (11.8) 41.9  (11.5) 41.9  (11.6)
Triglycerides  
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 5128 participants 5123 participants 10251 participants
156
(105 to 230)
154
(108 to 226)
155
(106 to 228)
Diabetes duration  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 5128 participants 5123 participants 10251 participants
10
(5 to 15)
10
(5 to 15)
10
(5 to 15)
1.Primary Outcome
Title 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.
Hide Description

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.

Time Frame 4.9 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to occurrence of MCE.
Arm/Group Title Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Hide Arm/Group Description:
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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
Overall Number of Participants Analyzed 5128 5123
Measure Type: Number
Unit of Measure: participants
503 543
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glycemia Trial: Intensive Control, Glycemia Trial: Standard Control
Comments Adjustment performed for the following pre-specified factors: sub-trial assignment (Blood Pressure Trial or Lipid Trial), assignment to intensive BP group in BP Trial, assignment to fenofibrate group in Lipid Trial, the seven clinical center networks, and presence of clinical cardiovascular disease at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments P-value presented is not adjusted for multiple comparisons. A priori significance level was 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.81 to 1.03
Estimation Comments [Not Specified]
2.Primary Outcome
Title First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.
Hide Description Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial.
Time Frame 4.7 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to occurrence of MCE.
Arm/Group Title BP Trial: Intensive Control BP Trial: Standard Control
Hide Arm/Group Description:
Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals.
Open label administration of multiple anti-hypertensive agents to maintain SBP level <140 mm Hg. Anti-hypertensive agents multiple anti-hypertensive agents as needed to reach Blood Pressure Trial arm-specific goals.
Overall Number of Participants Analyzed 2363 2371
Measure Type: Number
Unit of Measure: participants
208 237
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BP Trial: Intensive Control, BP Trial: Standard Control
Comments Recruitment for the Blood PressureTrial was designed to enroll 4200 participant to have 94% power to detect a 20% reduction in the rate of MCE for patients in the intensive-therapy group as compared with the standard-therapy group, assuming a two-sided alpha level of 0.05, a primary-outcome rate of 4% per year in the standard-therapy group, and a planned average follow-up of approximately 5.6 years.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments P-value is adjusted for interim monitoring. A priori significance level was 0.05.
Method Regression, Cox
Comments Adjustment for the seven clinical center networks and presence of clinical cardiovascular disease at baseline as pre-specified in the study protocol.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.06
Estimation Comments [Not Specified]
3.Primary Outcome
Title First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.
Hide Description Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants.
Time Frame 4.7 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to occurrence of MCE.
Arm/Group Title Lipid Trial: Fenofibrate Lipid Trial: Placebo
Hide Arm/Group Description:
Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2, in combination with open label simvastatin 20 - 40 mg/day.
Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m^2 or 54 mg/day in participants with eGFR <50 mL/min/1.73m^2, in combination with open label simvastatin 20 - 40 mg/day.
Overall Number of Participants Analyzed 2765 2753
Measure Type: Number
Unit of Measure: participants
291 310
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lipid Trial: Fenofibrate, Lipid Trial: Placebo
Comments Recruitment for the Glycemia Trial was designed to enroll 5800 participant to have 87% power to detect a 20% reduction in the rate of MCE for patients in the fenofibrate group as compared with the placebo group, assuming a two-sided alpha level of 0.05, a primary-outcome rate of 2.4% per year in the placebo group, and a planned average follow-up of approximately 5.6 years.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments P-value is adjusted for interim monitoring. A priori significance level was 0.05.
Method Regression, Cox
Comments Adjustment for the seven clinical center networks and presence of clinical cardiovascular disease at baseline as pre-specified in the study protocol.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.79 to 1.08
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Death From Any Cause in the Glycemia Trial.
Hide Description

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).

Time Frame 4.9 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to death.
Arm/Group Title Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Hide Arm/Group Description:
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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
Overall Number of Participants Analyzed 5128 5123
Measure Type: Number
Unit of Measure: participants
391 327
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Glycemia Trial: Intensive Control, Glycemia Trial: Standard Control
Comments Adjustment performed for the following pre-specified factors: sub-trial assignment (Blood Pressure Trial or Lipid Trial), assignment to intensive BP group in BP Trial, assignment to fenofibrate group in Lipid Trial, the seven clinical center networks, and presence of clinical cardiovascular disease at baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments P-value presented is not adjusted for multiple comparisons. A priori significance level was 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
1.03 to 1.38
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Stroke in the Blood Pressure Trial.
Hide Description Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial.
Time Frame 4.7 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior to occurrence of stroke.
Arm/Group Title BP Trial: Intensive Control BP Trial: Standard Control
Hide Arm/Group Description:
Open label administration of anti-hypertensive agents to reduce and maintain systolic blood pressure (SBP) level to <120 mmHg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.
Open label administration of multiple anti-hypertensive agents to maintain SBP level to <140 mm Hg. Anti-hypertensive agents include multiple anti-hypertensive medications as needed to reach Blood Pressure Trial arm-specific goals.
Overall Number of Participants Analyzed 2363 2371
Measure Type: Number
Unit of Measure: participants
36 62
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BP Trial: Intensive Control, BP Trial: Standard Control
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments P-value presented is not adjusted for multiple comparisons. A priori significance level was 0.05.
Method Regression, Cox
Comments Adjustment for the seven clinical center networks and presence of clinical cardiovascular disease at baseline as pre-specified in the study protocol.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.39 to 0.89
Estimation Comments [Not Specified]
6.Secondary Outcome
Title First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.
Hide Description Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants.
Time Frame 4.7 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The population analyzed included all participants randomized and was performed by intention to treat with right-censoring of participants who did not complete follow-up prior occurrence of event.
Arm/Group Title Lipid Trial: Fenofibrate Lipid Trial: Placebo
Hide Arm/Group Description:
Double blind administration of 160 mg/day of fenofibrate in participants with estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m^2 or 54 mg/day in patients with eGFR <50 mL/min/1.73m^2, in combination with open label simvastatin 20 - 40 mg/day.
Double blind administration of placebo matching either 160 mg/day in participants with eGFR ≥50 mL/min/1.73m^2 or 54 mg/day in participants with eGFR <50 mL/min/1.73m^2, in combination with open label simvastatin 20 - 40 mg/day.
Overall Number of Participants Analyzed 2765 2753
Measure Type: Number
Unit of Measure: participants
641 667
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lipid Trial: Fenofibrate, Lipid Trial: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments P-value presented is not adjusted for multiple comparisons. A priori significance level was 0.05.
Method Regression, Cox
Comments Adjustment for the seven clinical center networks and presence of clinical cardiovascular disease at baseline as pre-specified in the study protocol.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.85 to 1.05
Estimation Comments [Not Specified]
Time Frame Includes Serious Adverse Events (SAEs) reported after randomization and throughout the planned observation period, mean follow-up was 4.9 years. Data on other (non-serious) adverse events were not collected.
Adverse Event Reporting Description SAEs were defined as any adverse experience that was significantly life threatening and/or resulted in death, permanent disability, hospitalization or prolongation of hospitalization, myositis/myopathy, or hepatitis and were considered by the investigators to be possibly, probably, or definitely related to study treatments.
 
Arm/Group Title Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Hide Arm/Group Description 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%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals. 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 to 7.9%. Anti-hyperglycemic agents include multiple drugs including insulins and oral anti-hyperglycemic agents as needed to reach Glycemia Trial arm-specific goals.
All-Cause Mortality
Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Affected / at Risk (%) Affected / at Risk (%)
Total   137/5128 (2.67%)   107/5123 (2.09%) 
Cardiac disorders     
Congestive heart failure   34/5128 (0.66%)  12/5123 (0.23%) 
Bradycardia, tachycardia, atrial fibrillation *  13/5128 (0.25%)  4/5123 (0.08%) 
Angina/chest pain   4/5128 (0.08%)  5/5123 (0.10%) 
Myocardial infarction   4/5128 (0.08%)  5/5123 (0.10%) 
Endocrine disorders     
Pancreatitis *  5/5128 (0.10%)  8/5123 (0.16%) 
Ketoacidosis *  1/5128 (0.02%)  0/5123 (0.00%) 
Hypoglycemia (fatal) *  0/5128 (0.00%)  1/5123 (0.02%) 
Eye disorders     
Macular edema *  1/5128 (0.02%)  1/5123 (0.02%) 
Blurred vision *  1/5128 (0.02%)  1/5123 (0.02%) 
Gastrointestinal disorders     
Cholecystitis *  5/5128 (0.10%)  11/5123 (0.21%) 
Hepatitis/liver failure *  2/5128 (0.04%)  3/5123 (0.06%) 
Elevated creatinine, hyponatremia *  2/5128 (0.04%)  1/5123 (0.02%) 
Gastrointestinal bleeding *  1/5128 (0.02%)  1/5123 (0.02%) 
General disorders     
Hyperkalemia *  6/5128 (0.12%)  5/5123 (0.10%) 
Hyponatremia *  0/5128 (0.00%)  4/5123 (0.08%) 
Severe fluid retention *  3/5128 (0.06%)  1/5123 (0.02%) 
Dehydration *  1/5128 (0.02%)  2/5123 (0.04%) 
Vertigo *  0/5128 (0.00%)  1/5123 (0.02%) 
Anemia *  0/5128 (0.00%)  1/5123 (0.02%) 
Hypomagnesemia *  0/5128 (0.00%)  1/5123 (0.02%) 
Hyperosmolar nonketotic coma *  1/5128 (0.02%)  0/5123 (0.00%) 
Toxic metabolic enecphalopathy *  1/5128 (0.02%)  0/5123 (0.00%) 
Immune system disorders     
Angioedema *  9/5128 (0.18%)  4/5123 (0.08%) 
Thrombocytopenia *  2/5128 (0.04%)  0/5123 (0.00%) 
Blood dyscrasia *  1/5128 (0.02%)  0/5123 (0.00%) 
Felodipine toxicity *  1/5128 (0.02%)  0/5123 (0.00%) 
Injury, poisoning and procedural complications     
Motor vehicle accident (fatal) *  3/5128 (0.06%)  2/5123 (0.04%) 
Musculoskeletal and connective tissue disorders     
Myositis *  2/5128 (0.04%)  3/5123 (0.06%) 
Rhabdomyolisis *  1/5128 (0.02%)  2/5123 (0.04%) 
Fractures *  1/5128 (0.02%)  2/5123 (0.04%) 
Weakness *  0/5128 (0.00%)  1/5123 (0.02%) 
Renal and urinary disorders     
Acute or chronic renal failure *  8/5128 (0.16%)  6/5123 (0.12%) 
Respiratory, thoracic and mediastinal disorders     
Shortness of breath *  1/5128 (0.02%)  0/5123 (0.00%) 
Vascular disorders     
Dizziness, hypotension, syncope *  19/5128 (0.37%)  17/5123 (0.33%) 
Edema   3/5128 (0.06%)  1/5123 (0.02%) 
Cerebrovacular accident   1/5128 (0.02%)  1/5123 (0.02%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Glycemia Trial: Intensive Control Glycemia Trial: Standard Control
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Tim Craven / Senior Biostatistician
Organization: Wake Forest School of Medicine
Phone: 336-716-6109
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00000620     History of Changes
Obsolete Identifiers: NCT00182910
Other Study ID Numbers: 123
N01HC95178 ( U.S. NIH Grant/Contract )
N01HC95179 ( U.S. NIH Grant/Contract )
N01HC95180 ( U.S. NIH Grant/Contract )
N01HC95181 ( U.S. NIH Grant/Contract )
N01HC95182 ( U.S. NIH Grant/Contract )
N01HC95183 ( U.S. NIH Grant/Contract )
N01HC95184 ( U.S. NIH Grant/Contract )
IAA#Y1HC9035 ( Other Grant/Funding Number: U.S. Centers for Disease Control )
IAA#Y1HC1010 ( Other Grant/Funding Number: U.S. Centers for Disease Control )
First Submitted: October 27, 1999
First Posted: October 28, 1999
Results First Submitted: September 5, 2014
Results First Posted: September 15, 2014
Last Update Posted: November 22, 2016