Evaluating How the Treatments in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Affect Diabetic Retinopathy (The ACCORD Eye Study)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00542178
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 3,472
• Locations: 7
• Arms: 6
• Duration (Months): 74
• Patients Per Site: 496
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

Diabetic retinopathy (DR) is an eye disease that can occur in people with diabetes and can cause poor vision or blindness. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study is examining the effect of various treatments on cardiovascular disease in people with diabetes. This current study will examine the effects of the ACCORD treatments on the progression of DR in people participating in the ACCORD study.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy	Drug: Hypoglycemic Agents; Drug: Standard glycemia control; Drug: Intensive BP treatment; Drug: Standard BP control; Drug: Fenofibrate; Drug: Simvastatin; Drug: Placebo	Phase 3

Detailed Description

DR is the most common diabetic eye disease and is the leading cause of blindness in adults in the United States. It is caused by damage to the blood vessels of the retina, which is the light-sensitive outer layer of the eye. Retinal blood vessels are often affected by the high blood sugar levels associated with diabetes. Older people have an increased risk of developing DR; however, DR is likely to occur earlier and be more severe in anyone who has poorly controlled diabetes. Almost everyone who has had diabetes for more than 30 years will eventually show signs of DR. Symptoms of DR include poor night vision, seeing spots in front of the eyes, blurred vision, and blindness. The ACCORD study is a study that is examining the effects of different treatments on cardiovascular disease in people with diabetes. Participants in the ACCORD study will receive one of eight different combinations of treatment, including blood sugar control, blood pressure control, and cholesterol-controlling medication. This study will enroll participants in the ACCORD study and will examine the effects of the study treatments on DR. The results from this study may be used to develop new treatments to help prevent diabetes-related blindness.

Study visits will occur at baseline and Year 4. At each study visit, participants will have an eye exam and specialized fundus photographs taken of the back of the eye and retina.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3472 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensive glycemia control A strategy of intensive glycemia treatment to HbA1c less than 6%	Drug: Hypoglycemic Agents; Multiple drugs including insulins and oral hypoglycemia agents for HbA1c less than 6%
Active Comparator: Standard glycemia control A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	Drug: Standard glycemia control; A strategy of glycemia drugs for HbA1c 7% - 7.9%
Experimental: Intensive BP control A strategy of BP treatment for SBP less than 120 mm Hg	Drug: Intensive BP treatment; A strategy of multiple BP agents to reduce SBP less than 120 mm Hg
Active Comparator: Standard BP control A strategy of BP treatment for SBP less than 140 mm Hg	Drug: Standard BP control; A strategy of BP drugs for SBP less than 140 mm Hg
Experimental: Fibrate Blinded fenofibrate + simvastatin 20-40 mg/d	Drug: Fenofibrate; Blinded fenofibrate; Drug: Simvastatin; Simvastatin 20-40 mg/d
Placebo Comparator: Fibrate Placebo Blinded placebo + simvastatin 20-40 mg/d	Drug: Simvastatin; Simvastatin 20-40 mg/d; Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Progression of Diabetic Retinopathy of at Least 3 Stages on the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale, or Development of Proliferative Diabetic Retinopathy Necessitating Photocoagulation Therapy or Vitrectomy [Measured at Year 4]

   Diabetic retinopathy status was defined according to the eye with the highest level on the ETDRS Final Severity Scale for Persons, as follows: no diabetic retinopathy, a level of less than 20; mild diabetic retinopathy, a level of 20; moderate nonproliferative diabetic retinopathy (NPDR), a level above 20 but less than 53; severe diabetic retinopathy, a level of 53 but less than 60; and proliferative diabetic retinopathy (PDR), a level of 60 or higher.

Secondary Outcome Measures

1. Loss of Visual Acuity [Measured at Year 4]

2. Cataract Extraction [Measured at Year 4]

3. Development or Progression of Macular Edema [Measured at Year 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participating in the ACCORD study

Exclusion Criteria:

• Has had laser photocoagulation for DR

• Has had vitrectomy surgery for DR

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Berman Center for Clinical Research	Minneapolis	Minnesota	United States	55404
2	Columbia University	New York	New York	United States	10032
3	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
4	Case Western Reserve University	Cleveland	Ohio	United States	44106-4951
5	Veterans Affairs	Memphis	Tennessee	United States	38104-2193
6	University of Washington	Seattle	Washington	United States	98109
7	McMaster University	Hamilton	Ontario	Canada	L8L 2X2

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• National Eye Institute (NEI)

Investigators

• Principal Investigator: Walter T. Ambrosius, PhD, Wake Forest University Health Sciences
• Principal Investigator: Emily Y. Chew, MD, National Eye Institute (NEI)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for the ACCORD Study Web site

Publications

• Chew 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. Epub 2007 Apr 13.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00542178
• Other Study ID Numbers: 509; N01HC95178-19
• First Posted: Oct 10, 2007
• Last Update Posted: Jul 24, 2018
• Last Verified: Oct 1, 2016

• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Type 2 Diabetes Mellitus; Cardiovascular Diseases
• Additional relevant MeSH terms: Retinal Diseases; Diabetic Retinopathy; Hypoglycemic Agents; Simvastatin; Fenofibrate

Study Results

Participant Flow

Recruitment Details	Recruitment for the ACCORD Eye study was restricted to participants recruited as part of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The ACCORD Eye study began in October 2003, with 3472 participants enrolled by February 2006.
Pre-assignment Detail	All participants were enrolled in either the intensive or standard glycemia control arms. In addition to inclusion in the glycemia control part of the trial, participants were included as either part of the blood pressure trial (randomized to intensive or standard) OR the lipid trial (fibrate or fibrate placebo).

Arm/Group Title	Intensive Glycemia Control & Intensive Blood Pressure Control	Standard Glycemia Control & Intensive Blood Pressure Control	Intensive Glycemia Control & Standard Blood Pressure Control	Standard Glycemia Control & Standard Blood Pressure Control	Intensive Glycemia Control & Fibrate	Standard Glycemia Control & Fibrate	Intensive Glycemia Control & Fibrate Placebo	Standard Glycemia Control & Fibrate Placebo
Arm/Group Description	Intensive Glycemia Control: A strategy of intensive glycemia treatment to HbA1c less than 6% Intensive Blood Pressure Control: A strategy of BP treatment for SBP less than 120 mm Hg	Standard Glycemia Control: A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9% Intensive Blood Pressure Control: A strategy of BP treatment for SBP less than 120 mm Hg	Intensive Glycemia Control: A strategy of intensive glycemia treatment to HbA1c less than 6% Standard Blood Pressure Control: A strategy of BP treatment for SBP less than 140 mm Hg	Standard Glycemia Control: A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9% Standard Blood Pressure Control: A strategy of BP treatment for SBP less than 140 mm Hg	Intensive Glycemia Control: A strategy of intensive glycemia treatment to HbA1c less than 6% Fibrate: Blinded fenofibrate + simvastatin 20-40 mg/d	Standard Glycemia Control: A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9% Fibrate: Blinded fenofibrate + simvastatin 20-40 mg/d	Intensive Glycemia Control: A strategy of intensive glycemia treatment to HbA1c less than 6% Fibrate Placebo: Blinded placebo + simvastatin 20-40 mg/d	Standard Glycemia Control: A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9% Fibrate Placebo: Blinded placebo + simvastatin 20-40 mg/d
Period Title: Overall Study
STARTED	390	412	382	370	464	495	493	466
COMPLETED	315	332	308	308	400	406	406	381
NOT COMPLETED	75	80	74	62	64	89	87	85

Baseline Characteristics

Arm/Group Title	Intensive Glycemia Control	Standard Glycemia Control	Intensive BP Control	Standard BP Control	Fibrate	Fibrate Placebo	Total
Arm/Group Description	A strategy of intensive glycemia treatment to HbA1c less than 6%	A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	A strategy of BP treatment for SBP less than 120 mm Hg	A strategy of BP treatment for SBP less than 140 mm Hg	Blinded fenofibrate + simvastatin 20-40 mg/d	Blinded placebo + simvastatin 20-40 mg/d	Total of all reporting groups
Overall Participants	1429	1427	647	616	806	787	5712
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (6.4)	61.5 (6.3)	61.3 (6.1)	61.5 (6.6)	61.9 (6.2)	61.5 (6.5)	61.6 (6.3)
Sex: Female, Male (Count of Participants)
Female	538 37.6%	552 38.7%	1090 168.5%
Male	891 62.4%	875 61.3%	1766 273%
Female	310 21.7%	279 19.6%	247 38.2%	254 41.2%	1090 135.2%
Male	337 23.6%	337 23.6%	559 86.4%	533 86.5%	1766 219.1%
Duration of diabetes (year) [Mean (Standard Deviation) ]
Glycemic Control Study	9.8 (7.1)	10.1 (7.2)	10.0 (7.1)
Blood Pressure and Lipid Studies	10.1 (7.0)	10.3 (7.5)	9.7 (6.8)	9.8 (7.2)	10.0 (7.1)
Previous cardiovascular event (Count of Participants)
Previous cardiovascular event	452 31.6%	443 31%	895 138.3%
No previous cardiovascular event	977 68.4%	984 69%	1961 303.1%
Previous cardiovascular event	180 12.6%	197 13.8%	263 40.6%	255 41.4%	895 111%
No previous cardiovascular event	467 32.7%	419 29.4%	543 83.9%	532 86.4%	1961 243.3%
Race (Count of Participants)
Nonwhite race	427 29.9%	433 30.3%	860 132.9%
White race	1002 70.1%	994 69.7%	1996 308.5%
Nonwhite race	203 14.2%	201 14.1%	222 34.3%	234 38%	860 106.7%
White race	444 31.1%	415 29.1%	584 90.3%	553 89.8%	1996 247.6%
Glycated hemoglobin (percent) [Mean (Standard Deviation) ]
Glycemic Control Study	8.2 (1.0)	8.3 (1.0)	8.2 (1.0)
Blood Pressure and Lipid Studies	8.4 (1.1)	8.2 (1.0)	8.2 (1.0)	8.2 (1.0)	8.2 (1.0)
Cholesterol (HDL) (mg/dl) [Mean (Standard Deviation) ]
Glycemic Control Study	42.0 (11.4)	41.9 (11.1)	41.9 (11.3)
Blood Pressure and Lipid Studies	46.3 (12.8)	46.31 (13.8)	38.6 (7.8)	38.5 (7.9)	41.9 (11.3)
Cholesterol (LDL) (mg/dl) [Mean (Standard Deviation) ]
Glycemic Control Study	100.8 (33.4)	100.7 (32.1)	100.7 (32.7)
Blood Pressure and Lipid Studies	107.4 (37.0)	104.1 (33.5)	96.5 (29.7)	97.0 (30.1)	100.7 (32.7)
Triglycerides (mg/dl) [Mean (Standard Deviation) ]
Glycemic Control Study	196.1 (157.8)	194 (167.3)	195.1 (162.6)
Blood Pressure and Lipid Studies	200.7 (175.5)	204.7 (240.3)	190.1 (111.3)	187.9 (112.4)	195.1 (162.6)
Systolic Blood pressure (mm Hg) [Mean (Standard Deviation) ]
Glycemic Control Study	134.3 (16.6)	134.7 (17.4)	134.5 (17.0)
Blood Pressure and Lipid Studies	138.0 (16.7)	139.0 (14.7)	131.5 (17.0)	131.1 (17.5)	134.5 (17.0)
Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Glycemic Control Study	74.9 (10.3)	75.0 (10.6)	74.9 (10.5)
Blood Pressure and Lipid Studies	76.3 (10.5)	76.8 (9.9)	73.7 (10.5)	73.6 (10.5)	74.9 (10.5)
Urinary albumin:creatinine ratio (albumin (mg/dL): creatinin (g/dL)) [Mean (Standard Deviation) ]
Glycemic Control Study	69.5 (2228.9)	74.0 (275.3)	71.8 (253.1)
Blood Pressure and Lipid Studies	62.5 (197.6)	79.2 (269.9)	62.3 (180.2)	83.2 (331.5)	71.8 (253.1)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Glycemic Control Study	32.4 (5.5)	32.5 (5.4)	32.4 (5.5)
Blood Pressure and Lipid Studies	32.7 (5.7)	32.2 (5.3)	32.3 (5.5)	32.6 (5.4)	32.4 (5.5)
Visual acuity (letters) [Mean (Standard Deviation) ]
Glycemic Control Study	75.9 (10.4)	75.9 (10.0)	75.9 (10.2)
Blood Pressure and Lipid Studies	75.6 (10.3)	75.5 (10.2)	76.2 (9.7)	76.2 (10.7)	75.9 (10.2)
Smoking status (Count of Participants)
Never smoked	581 40.7%	607 42.5%	1188 183.6%
Former Smoker	657 46%	623 43.7%	1280 197.8%
Current Smoker	191 13.4%	196 13.7%	387 59.8%
Missing	0 0%	1 0.1%	1 0.2%
Never smoked	279 19.5%	263 18.4%	313 48.4%	333 54.1%	1188 147.4%
Former Smoker	279 19.5%	276 19.3%	373 57.7%	352 57.1%	1280 158.8%
Current Smoker	89 6.2%	77 5.4%	119 18.4%	102 16.6%	387 48%
Missing	0 0%	0 0%	1 0.2%	0 0%	1 0.1%
Severity of Diabetic Retinopathy (Count of Participants)
None	729 51%	721 50.5%	1450 224.1%
Mild	241 16.9%	277 19.4%	518 80.1%
Moderate Nonproliferative Diabetic Retinopathy	443 31%	404 28.3%	847 130.9%
Severe Nonproliferative Diabetic Retinopathy	5 0.3%	5 0.4%	10 1.5%
Proliferative diabetic retinopathy	10 0.7%	19 1.3%	29 4.5%
Missing	1 0.1%	1 0.1%	2 0.3%
None	328 23%	295 20.7%	429 66.3%	398 64.6%	1450 179.9%
Mild	105 7.3%	117 8.2%	141 21.8%	155 25.2%	518 64.3%
Moderate Nonproliferative Diabetic Retinopathy	195 13.6%	198 13.9%	230 35.5%	224 36.4%	847 105.1%
Severe Nonproliferative Diabetic Retinopathy	3 0.2%	1 0.1%	2 0.3%	4 0.6%	10 1.2%
Proliferative diabetic retinopathy	14 1%	5 0.4%	4 0.6%	6 1%	29 3.6%
Missing	2 0.1%	0 0%	0 0%	0 0%	2 0.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Progression of Diabetic Retinopathy of at Least 3 Stages on the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale, or Development of Proliferative Diabetic Retinopathy Necessitating Photocoagulation Therapy or Vitrectomy
Description	Diabetic retinopathy status was defined according to the eye with the highest level on the ETDRS Final Severity Scale for Persons, as follows: no diabetic retinopathy, a level of less than 20; mild diabetic retinopathy, a level of 20; moderate nonproliferative diabetic retinopathy (NPDR), a level above 20 but less than 53; severe diabetic retinopathy, a level of 53 but less than 60; and proliferative diabetic retinopathy (PDR), a level of 60 or higher.
Time Frame	Measured at Year 4

Outcome Measure Data

Analysis Population Description

The ACCORD Eye study recruited 3472 eligible participants. Of these, 2856 participants had both baseline and year 4 follow-up data available for analyses.

Arm/Group Title	Intensive Glycemia Control	Standard Glycemia Control	Intensive Blood Pressure Control	Standard Blood Pressure Control	Fenofibrate + Simvastatin Therapy	Placebo + Simvastatin Therapy
Arm/Group Description	Strategy of intensive glycemia treatment to HbA1c less than 6%	Strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	A strategy of BP treatment for SBP less than 120 mmHg	Strategy of BP treatment for SBP less than 140 mmHg	Blinded fenofibrate + simvastatin 20-40 mg/d	Blinded placebo + simvastatin 20-40 mg/d
Measure Participants	1429	1427	647	616	806	787
Number [participants]	104 7.3%	149 10.4%	67 10.4%	54 8.8%	52 6.5%	80 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Glycemia Control, Standard Glycemia Control
	Comments	Our recruitment goal for the ACCORD Eye study was set in order to achieve a statistical power of 88% to detect a 15% relative reduction with intensive glycemic control as compared with standard glycemic control
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments	Comparisons made using likelihood-ratio tests from logistic-regression models with adjustment for same study-design factors used in ACCORD analysis
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intensive Blood Pressure Control, Standard Blood Pressure Control
	Comments	Our recruitment goal for the ACCORD Eye study was set in order to achieve a statistical power of 80% to detect a 20% relative reduction with intensive blood pressure control as compared with standard blood pressure control
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Regression, Logistic
	Comments	Comparisons made using likelihood-ratio tests from logistic-regression models with adjustment for same study-design factors used in ACCORD analysis
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fenofibrate + Simvastatin Therapy, Placebo + Simvastatin Therapy
	Comments	Our recruitment goal for the ACCORD Eye study was set in order to achieve a statistical power of 91% to detect a 20% relative reduction with lipid control with a statin and fenofibrate as compared with lipid control with a statin alone
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Regression, Logistic
	Comments	Comparisons made using likelihood-ratio tests from logistic-regression models with adjustment for same study-design factors used in ACCORD analysis
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.60
	Confidence Interval	(2-Sided) 95%; 0.42 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Loss of Visual Acuity
Time Frame	Measured at Year 4

Outcome Measure Data

Analysis Population Description

Subset of Participants from the entire ACCORD cohort (NCT00000620) who provided information about loss in visual acuity.

Arm/Group Title	Intensive Glycemia Control	Standard Glycemia Control	Intensive Blood Pressure Control	Standard Blood Pressure Control	Fenofibrate + Simvastatin Therapy	Placebo + Simvastatin Therapy
Arm/Group Description	Strategy of intensive glycemia treatment to HbA1c less than 6%	Strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	A strategy of BP treatment for SBP less than 120 mmHg	Strategy of BP treatment for SBP less than 140 mmHg	Blinded fenofibrate + simvastatin 20-40 mg/d	Blinded placebo + simvastatin 20-40 mg/d
Measure Participants	3466	3511	1629	1617	1883	1848
Count of Participants [Participants]	744 52.1%	752 52.7%	367 56.7%	382 62%	354 43.9%	393 49.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Glycemia Control, Standard Glycemia Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.997
	Confidence Interval	(2-Sided) 95%; 0.901 to 1.104
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intensive Blood Pressure Control, Standard Blood Pressure Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.952
	Confidence Interval	(2-Sided) 95%; 0.825 to 1.099
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fenofibrate + Simvastatin Therapy, Placebo + Simvastatin Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.880
	Confidence Interval	(2-Sided) 95%; 0.762 to 1.016
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Cataract Extraction
Time Frame	Measured at Year 4

Outcome Measure Data

Analysis Population Description

Subset of Participants from the entire ACCORD cohort (NCT00000620) who provided information regarding whether or not they had a cataract extraction.

Arm/Group Title	Intensive Glycemia Control	Standard Glycemia Control	Intensive Blood Pressure Control	Standard Blood Pressure Control	Fenofibrate + Simvastatin Therapy	Placebo + Simvastatin Therapy
Arm/Group Description	Strategy of intensive glycemia treatment to HbA1c less than 6%	Strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	A strategy of BP treatment for SBP less than 120 mmHg	Strategy of BP treatment for SBP less than 140 mmHg	Blinded fenofibrate + simvastatin 20-40 mg/d	Blinded placebo + simvastatin 20-40 mg/d
Measure Participants	4361	4405	2053	2039	2333	2341
Count of Participants [Participants]	547 38.3%	623 43.7%	266 41.1%	300 48.7%	305 37.8%	299 38%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Glycemia Control, Standard Glycemia Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0355
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.884
	Confidence Interval	(2-Sided) 95%; 0.788 to 0.992
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intensive Blood Pressure Control, Standard Blood Pressure Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.891
	Confidence Interval	(2-Sided) 95%; 0.755 to 1.051
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fenofibrate + Simvastatin Therapy, Placebo + Simvastatin Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.015
	Confidence Interval	(2-Sided) 95%; 0.865 to 1.190
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Development or Progression of Macular Edema
Time Frame	Measured at Year 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Glycemia Control	Standard Glycemia Control	Intensive Blood Pressure Control	Standard Blood Pressure Control	Fenofibrate + Simvastatin Therapy	Placebo + Simvastatin Therapy
Arm/Group Description	Strategy of intensive glycemia treatment to HbA1c less than 6%	Strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%	A strategy of BP treatment for SBP less than 120 mmHg	Strategy of BP treatment for SBP less than 140 mmHg	Blinded fenofibrate + simvastatin 20-40 mg/d	Blinded placebo + simvastatin 20-40 mg/d
Measure Participants	1413	1399	633	609	791	779
Count of Participants [Participants]	44 3.1%	40 2.8%	18 2.8%	20 3.2%	24 3%	22 2.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Glycemia Control, Standard Glycemia Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Intensive Blood Pressure Control, Standard Blood Pressure Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fenofibrate + Simvastatin Therapy, Placebo + Simvastatin Therapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Entire duration of the study
Adverse Event Reporting Description	Adverse events were collected as part of the ACCORD main trial (NCT00000620). No adverse events were collected as part of the ACCORD-Eye Study.
Arm/Group Title	Intensive Glycemia Control		Standard Glycemia Control		Intensive BP Control		Standard BP Control		Fibrate		Fibrate Placebo
Arm/Group Description	A strategy of intensive glycemia treatment to HbA1c less than 6%		A strategy of multiple drugs to treat HbA1c to 7.0% - 7.9%		A strategy of BP treatment for SBP less than 120 mm Hg		A strategy of BP treatment for SBP less than 140 mm Hg		Blinded fenofibrate + simvastatin 20-40 mg/d		Blinded placebo + simvastatin 20-40 mg/d
All Cause Mortality
	Intensive Glycemia Control		Standard Glycemia Control		Intensive BP Control		Standard BP Control		Fibrate		Fibrate Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Intensive Glycemia Control		Standard Glycemia Control		Intensive BP Control		Standard BP Control		Fibrate		Fibrate Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Intensive Glycemia Control		Standard Glycemia Control		Intensive BP Control		Standard BP Control		Fibrate		Fibrate Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The glycemia trial was stopped early, potentially underestimating the reported effect of glycemia treatment on diabetic retinopathy.

More Information

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.