Age-Related Eye Disease Study 2 (AREDS2)
Study Details
Study Description
Brief Summary
Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk. AREDS2 was designed to test whether adding lutein + zeaxanthin, DHA + EPA, or lutein + zeaxanthin and DHA + EPA to the AREDS formulation might further reduce the risk of progression to advanced AMD. A secondary goal was to test the effects of eliminating beta carotene and reducing zinc dose in the AREDS formulation.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
AREDS2 was a randomized, double-masked, placebo-controlled, 2x2 factorial trial evaluating the risks and benefits of adding lutein (10 mg) + zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), or both to the AREDS formulation, which consisted of vitamins C (500 mg), vitamin E (400 international units), beta carotene (15 mg), zinc (80 mg as zinc oxide), and copper (2 mg as cupric oxide) for the treatment of progression to advanced AMD. The study enrolled 4,203 participants aged 50 to 85 years, with sufficiently clear ocular media to allow accurate assessment of AMD from fundus photographs. Subjects were enrolled on the basis of the AREDS Simplified Severity Scale for defining risk categories for development of advanced age-related macular degeneration. All participants were offered additional treatment with the original AREDS formulation (now considered standard of care) and 3 variations of this formula. These are: (1) no beta-carotene; (2) lower amount of zinc (25 mg); and (3) no beta-carotene and lower amount of zinc (25 mg). Eligible participants were followed for a minimum of five years.
Multiple ancillary studies were conducted using the parent study (AREDS2) data to explore:
-
Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
-
Outcome is measured with a battery of tests administered over the telephone at baseline, and at years 2 and 4 of the study.
-
Primary outcome is the change in the composite score for the results of the cognitive function testing from baseline over time.
-
Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
- Primary measure of cardiovascular morbidity and mortality
- Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
- Primary outcome is the development of peripheral drusen, geographic atrophy, reticular pigmentary changes, and pseudoreticular drusen.
- Association of genotype polymorphisms with age-related macular degeneration and cataract
- Whole genome sequencing will be completed. Evaluation of association genetic associations with disease will be conducted using AREDS controls.
- Association of genotype polymorphisms with progression of age-related macular degeneration
- Whole genome sequencing is conducted. Progression from early to late and severe stages of AMD will be examined with the genotype data to evaluate the risks of progression associated with the genotype polymorphisms.
-
Association of genotype polymorphisms with dietary intake a. Whole genome sequencing is conducted. Progression from early to late and severe stages of AMD will be examined regarding potential interaction of the dietary intake with the genotype data to evaluate the risks of progression.
-
Association of genotype polymorphisms with AREDS2 supplements a. Interaction of genetic polymorphisms with AREDS2 supplements for progression to late AMD will be evaluated using the data from the whole genome sequencing project.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Lutein/Zeaxanthin lutein (10mg)/zeaxanthin (2 mg) |
Dietary Supplement: Lutein/zeaxanthin
10 mg lutein and 2 mg zeaxanthin (1 tablet) Placebo-DHA/EPA (2 soft-gel capsules)
|
Active Comparator: DHA/EPA DHA (350 mg)/EPA (650 mg) |
Dietary Supplement: DHA/EPA
Placebo-lutein/zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)
Other Names:
|
Active Comparator: Lutein/Zeaxanthin + DHA/EPA lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) |
Drug: Lutein/zeaxanthin and DHA/EPA
10 mg lutein and 2 mg zeaxanthin (1 tablet) 350 mg DHA and 650 mg EPA (2 soft-gel capsules)
|
Placebo Comparator: Placebo/Control Considered control because all participants received the AREDS formulation |
Outcome Measures
Primary Outcome Measures
- Development of Advanced AMD in People at Moderate to High Risk for Progression. [5 years of follow-up]
Defined as central geographic atrophy or retinal features of choroidal neovascularization detected on central grading of the stereoscopic fundus photographs or a history of treatment for advanced AMD after study enrollment.
Secondary Outcome Measures
- Progression to Moderate Vision Loss [5 years of follow-up]
Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization
- Adverse Events [5 years of follow-up]
Safety outcomes included serious adverse events and mortality.
- Progression to Cataract Surgery [5 years of follow-up]
The study examined the effects of lutein/zeaxanthin on progression to cataract surgery with data collected during regular telephone contacts and the annual study visits.
Other Outcome Measures
- Incident Cardiovascular Disease [5 years of follow-up]
Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
- Cognition as Measured by a Telephone Battery [5 years of follow-up]
Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
- Prevalence of Peripheral Changes as Measured Using OPTOS Imaging [5 years of follow-up]
Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
- Genetics for the Association of AMD and Cataract [5 years of follow-up]
- Genetics for the Progression of AMD and Cataract [5 years of follow-up]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men and women between the ages of 50 and 85 years
-
Macular status ranges from large drusen in both eyes or large drusen in one eye and advanced AMD (neovascular AMD or geographic atrophy) in the fellow eye
Exclusion Criteria:
- Ocular media not clear enough to allow good fundus photography
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294 |
2 | Jones Eye Institute - UAMS | Little Rock | Arkansas | United States | 72205 |
3 | Retina-Vitreous Associates Medical Group | Beverly Hills | California | United States | 90211 |
4 | Shiley Eye Center - UCSD | La Jolla | California | United States | 92093 |
5 | Loma Linda University | Loma Linda | California | United States | 92354 |
6 | Doheny Eye Institute | Los Angeles | California | United States | 90033 |
7 | Jules Stein Eye Institute | Los Angeles | California | United States | 90095 |
8 | VA Northern California Health Care System | Martinez | California | United States | 94553 |
9 | Southern California Desert Retina Consultants, MC | Palm Springs | California | United States | 92262 |
10 | University of California, Davis | Sacramento | California | United States | 95817 |
11 | West Coast Retina Medical Group, Inc | San Francisco | California | United States | 94107 |
12 | Pacific Eye Associates | San Francisco | California | United States | 94115 |
13 | Colorado Retina Associates | Denver | Colorado | United States | 80218 |
14 | Eldorado Retina Associates, PC | Louisville | Colorado | United States | 80027 |
15 | Yale University Eye Center | New Haven | Connecticut | United States | 06510 |
16 | Retina Group of Florida | Ft. Lauderdale | Florida | United States | 33334 |
17 | University of Florida | Jacksonville | Florida | United States | 32209 |
18 | Bascom Palmer Eye Institute | Miami | Florida | United States | 33136 |
19 | Sarasota Retina Institute | Sarasota | Florida | United States | 34239 |
20 | Center for Retina and Macular Disease | Winter Haven | Florida | United States | 33880 |
21 | Emory University Eye Center | Atlanta | Georgia | United States | 30322 |
22 | Georgia Retina, PC | Decatur | Georgia | United States | 30030 |
23 | Northwestern University | Chicago | Illinois | United States | 60611 |
24 | The University of Illinois | Chicago | Illinois | United States | 60612 |
25 | NorthShore University HealthSystems | Glenview | Illinois | United States | 60026 |
26 | Ingalls Memorial Hospital | Harvey | Illinois | United States | 60426 |
27 | University of Iowa | Iowa City | Iowa | United States | 52242 |
28 | Retina Associates of Kentucky | Lexington | Kentucky | United States | 40509 |
29 | Paducah Retinal Center | Paducah | Kentucky | United States | 42001 |
30 | Elman Retina Group | Baltimore | Maryland | United States | 21237 |
31 | Wilmer Eye Institute, Johns Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
32 | National Eye Institute | Bethesda | Maryland | United States | 20892 |
33 | The Retina Group of Washington | Chevy Chase | Maryland | United States | 20815 |
34 | Massachusetts Eye and Ear Infirmary | Boston | Massachusetts | United States | 02114 |
35 | Ophthalmic Consultants of Boston | Boston | Massachusetts | United States | 02114 |
36 | Kresge Eye Institute | Detroit | Michigan | United States | 48201 |
37 | Henry Ford Health System - Eye Care Services | Detroit | Michigan | United States | 48202 |
38 | Vision Research Foundation | Grand Rapids | Michigan | United States | 49546 |
39 | Vision Research Foundation | Royal Oak | Michigan | United States | 48073 |
40 | Vision Research Foundation | Traverse City | Michigan | United States | 49686 |
41 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
42 | University Health Care - Mason Eye Institute | Columbia | Missouri | United States | 65212 |
43 | Eye Foundation of Kansas City | Kansas City | Missouri | United States | 64108 |
44 | Mid-America Retina Consultants, PA | Kansas City | Missouri | United States | 64111 |
45 | The Retina Institute | St Louis | Missouri | United States | 63110 |
46 | Washington University School of Medicine | St. Louis | Missouri | United States | 63110 |
47 | Delaware Valley Retina Associates | Lawrenceville | New Jersey | United States | 08648 |
48 | UMDNJ | Newark | New Jersey | United States | 07103 |
49 | Ophthalmic Consultants of Long Island | Lynbrook | New York | United States | 11563 |
50 | New York Eye and Ear Infirmary | New York | New York | United States | 10003 |
51 | Manhattan Eye, Ear and Throat Hospital | New York | New York | United States | 10021 |
52 | University of Rochester Eye Institute | Rochester | New York | United States | 14642 |
53 | Retina Consultants, PLLC | Slingerlands | New York | United States | 12159 |
54 | The Research Foundation of SUNY/Stony Brook | Stony Brook | New York | United States | 11794 |
55 | Western Carolina Retinal Associates | Asheville | North Carolina | United States | 28803 |
56 | UNC Department of Ophthalmology | Chapel Hill | North Carolina | United States | 27599 |
57 | Charlotte Eye Ear Nose and Throat Associates | Charlotte | North Carolina | United States | 28210 |
58 | Duke University | Durham | North Carolina | United States | 27710 |
59 | Wake Forest University Eye Center | Winston-Salem | North Carolina | United States | 27157 |
60 | Case Western Reserve University | Cleveland | Ohio | United States | 44106 |
61 | Retina Associates of Cleveland | Cleveland | Ohio | United States | 44122 |
62 | Ohio State University | Columbus | Ohio | United States | 43210 |
63 | Retina Associates of Cleveland | Middleburg Heights | Ohio | United States | 44130 |
64 | Retina Associates of Cleveland | Youngstown | Ohio | United States | 44505 |
65 | Dean McGee Eye Institute | Oklahoma City | Oklahoma | United States | 73104 |
66 | Devers Eye Institute | Portland | Oregon | United States | 97210 |
67 | Retina Northwest, PC | Portland | Oregon | United States | 97210 |
68 | Pennsylvania Retina Specialists, PC | Camp Hill | Pennsylvania | United States | 17011 |
69 | Penn State M.S. Hershey Medical Center | Hershey | Pennsylvania | United States | 17033 |
70 | Scheie Eye Institute | Philadelphia | Pennsylvania | United States | 19104 |
71 | Wills Eye Hospital/Mid Atlantic Retina | Philadelphia | Pennsylvania | United States | 19107 |
72 | Retina Vitreous Consultants | Pittsburgh | Pennsylvania | United States | 15213 |
73 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15213 |
74 | Palmetto Retina Center | Columbia | South Carolina | United States | 29204 |
75 | Carolina Retina Center | Columbia | South Carolina | United States | 29223 |
76 | Southeastern Retina Associates, PC | Knoxville | Tennessee | United States | 37909 |
77 | University of Tennessee | Memphis | Tennessee | United States | 38163 |
78 | Vanderbilt Eye Institute | Nashville | Tennessee | United States | 37232 |
79 | Texas Retina Associates | Arlington | Texas | United States | 76012 |
80 | Texas Retina Associates | Dallas | Texas | United States | 75231 |
81 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
82 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
83 | Retina Consultants of Houston | Houston | Texas | United States | 77030 |
84 | Texas Retina Associates | Lubbock | Texas | United States | 79424 |
85 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
86 | John Moran Eye Center | Salt Lake City | Utah | United States | 84132 |
87 | Fletcher Allen Health Care | Burlington | Vermont | United States | 05401 |
88 | The Retina Group of Washington | Fairfax | Virginia | United States | 22031 |
89 | Retina Center Northwest | Silverdale | Washington | United States | 98383 |
90 | University of Wisconsin | Madison | Wisconsin | United States | 53705 |
91 | The Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- National Eye Institute (NEI)
- National Heart, Lung, and Blood Institute (NHLBI)
- Office of Dietary Supplements (ODS)
- National Center for Complementary and Integrative Health (NCCIH)
Investigators
- Study Chair: Emily Y Chew, MD, National Eye Institute, National Institutes of Health
- Study Director: John Paul SanGiovanni, Sc.D., National Eye Institute, National Institutes of Health
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- NEI-120
- N01-EY-5-0007
- HHS-N-260-2005-00007-C
- CC-070025
- 07-EI-0025
- NCT00409513
Study Results
Participant Flow
Recruitment Details | Between October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites. |
---|---|
Pre-assignment Detail | Prior to randomization, participants had to complete the Qualification phase. They could only be randomized if they took at least 75% of the run-in medication. |
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA |
---|---|---|---|---|
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) |
Period Title: Overall Study | ||||
STARTED | 1012 | 1044 | 1068 | 1079 |
COMPLETED | 1007 | 1038 | 1062 | 1069 |
NOT COMPLETED | 5 | 6 | 6 | 10 |
Baseline Characteristics
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA | Total |
---|---|---|---|---|---|
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) | Total of all reporting groups |
Overall Participants | 1012 | 1044 | 1068 | 1079 | 4203 |
Age (Median) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [Participants] |
74
7.3%
|
74
7.1%
|
74
6.9%
|
75
7%
|
74
1.8%
|
Sex: Female, Male (Count of Participants) | |||||
Female |
548
54.2%
|
596
57.1%
|
603
56.5%
|
641
59.4%
|
2388
56.8%
|
Male |
464
45.8%
|
448
42.9%
|
465
43.5%
|
438
40.6%
|
1815
43.2%
|
Outcome Measures
Title | Development of Advanced AMD in People at Moderate to High Risk for Progression. |
---|---|
Description | Defined as central geographic atrophy or retinal features of choroidal neovascularization detected on central grading of the stereoscopic fundus photographs or a history of treatment for advanced AMD after study enrollment. |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
Intention to Treat. Participants lost to follow-up during the course of the study were censored at the time of last contact. |
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA |
---|---|---|---|---|
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) |
Measure Participants | 1007 | 1038 | 1062 | 1069 |
Measure Eyes | 1691 | 1709 | 1749 | 1742 |
Number [Eyes] |
493
|
468
|
507
|
472
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin |
---|---|---|
Comments | Each of the 3 active arms was compared to the placebo/control arm. | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.013 |
Comments | Adjusted for 3 treatment versus placebo comparisons and interim analyses | |
Method | Regression, Cox | |
Comments | Adjusted for baseline AMD status | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.90 | |
Confidence Interval |
(2-Sided) 98.7% 0.76 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The reference group is placebo. |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, DHA/EPA |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.013 |
Comments | Adjusted for multiple comparisons | |
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.97 | |
Confidence Interval |
(2-Sided) 98.7% 0.82 to 1.16 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin + DHA/EPA |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.013 |
Comments | ||
Method | Regression, Cox | |
Comments | Adjusted for multiple comparisons | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.89 | |
Confidence Interval |
(2-Sided) 98.7% 0.75 to 1.06 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Progression to Moderate Vision Loss |
---|---|
Description | Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA |
---|---|---|---|---|
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) |
Measure Participants | 1007 | 1038 | 1062 | 1069 |
Measure Eyes | 1630 | 1660 | 1694 | 1672 |
Number [Eyes] |
515
|
509
|
519
|
506
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.95 | |
Confidence Interval |
(2-Sided) 95% 0.84 to 1.08 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, DHA/EPA |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% 0.84 to 1.09 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin + DHA/EPA |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.94 | |
Confidence Interval |
(2-Sided) 95% 0.83 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Adverse Events |
---|---|
Description | Safety outcomes included serious adverse events and mortality. |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
Number of deaths in 5 years |
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA |
---|---|---|---|---|
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) |
Measure Participants | 1012 | 1044 | 1068 | 1079 |
Mortality |
81
8%
|
87
8.3%
|
96
9%
|
104
9.6%
|
Serious Adverse Events |
479
47.3%
|
484
46.4%
|
505
47.3%
|
519
48.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin |
---|---|---|
Comments | Comparison of Lutein/Zeaxantin versus Control for mortality | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.04 | |
Confidence Interval |
(2-Sided) 95% 0.77 to 1.40 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, DHA/EPA |
---|---|---|
Comments | Comparison of DHA/EPA versus Placebo for mortality | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.13 | |
Confidence Interval |
(2-Sided) 95% 0.84 to 1.52 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin + DHA/EPA |
---|---|---|
Comments | Comparison of Lutein/Zeaxanthin + DHA/EPA versus Placebo for Mortality | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.23 | |
Confidence Interval |
(2-Sided) 95% 0.92 to 1.65 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Progression to Cataract Surgery |
---|---|
Description | The study examined the effects of lutein/zeaxanthin on progression to cataract surgery with data collected during regular telephone contacts and the annual study visits. |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
Includes participants who were phakic in at least 1 eye at baseline |
Arm/Group Title | No Lutein/Zeaxanthin | Lutein/Zeaxanthin |
---|---|---|
Arm/Group Description | Lutein main effect - includes participants who did not receive Lutein/Zeaxanthin | Lutein main effect - includes all participants who received Lutein/Zeaxanthin |
Measure Participants | 1577 | 1578 |
Measure Eyes | 3022 | 3005 |
Number [Eyes] |
708
|
681
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo/Control, Lutein/Zeaxanthin |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.05 |
Comments | ||
Method | Regression, Cox | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% 0.84 to 1.10 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Incident Cardiovascular Disease |
---|---|
Description | Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Cognition as Measured by a Telephone Battery |
---|---|
Description | Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Prevalence of Peripheral Changes as Measured Using OPTOS Imaging |
---|---|
Description | Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Genetics for the Association of AMD and Cataract |
---|---|
Description | |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Genetics for the Progression of AMD and Cataract |
---|---|
Description | |
Time Frame | 5 years of follow-up |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | 5 years | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Adverse events reported by System Organ Class | |||||||
Arm/Group Title | Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA | ||||
Arm/Group Description | Considered control because all participants received the AREDS formulation | lutein (10mg)/zeaxanthin (2 mg) | DHA (350 mg)/EPA (650 mg) | lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg) | ||||
All Cause Mortality |
||||||||
Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 479/1012 (47.3%) | 484/1044 (46.4%) | 505/1068 (47.3%) | 519/1079 (48.1%) | ||||
Blood and lymphatic system disorders | ||||||||
Blood and lymphatic system disorders | 12/1012 (1.2%) | 14 | 11/1044 (1.1%) | 11 | 9/1068 (0.8%) | 10 | 7/1079 (0.6%) | 7 |
Cardiac disorders | ||||||||
Cardiac Disorders | 96/1012 (9.5%) | 122 | 110/1044 (10.5%) | 138 | 119/1068 (11.1%) | 144 | 103/1079 (9.5%) | 133 |
Congenital, familial and genetic disorders | ||||||||
Congenital, familian and genetic disorders | 3/1012 (0.3%) | 3 | 1/1044 (0.1%) | 1 | 0/1068 (0%) | 0 | 0/1079 (0%) | 0 |
Ear and labyrinth disorders | ||||||||
Ear and labyrinth disorders | 7/1012 (0.7%) | 7 | 3/1044 (0.3%) | 3 | 4/1068 (0.4%) | 4 | 1/1079 (0.1%) | 1 |
Endocrine disorders | ||||||||
Endocrine disorders | 2/1012 (0.2%) | 2 | 3/1044 (0.3%) | 3 | 3/1068 (0.3%) | 3 | 0/1079 (0%) | 0 |
Eye disorders | ||||||||
Eye disorders | 3/1012 (0.3%) | 3 | 11/1044 (1.1%) | 13 | 4/1068 (0.4%) | 6 | 0/1079 (0%) | 0 |
Gastrointestinal disorders | ||||||||
Gastrointestinal disorders | 76/1012 (7.5%) | 101 | 69/1044 (6.6%) | 81 | 58/1068 (5.4%) | 72 | 61/1079 (5.7%) | 71 |
General disorders | ||||||||
General disorders and administration site conditions | 54/1012 (5.3%) | 60 | 50/1044 (4.8%) | 54 | 51/1068 (4.8%) | 58 | 46/1079 (4.3%) | 50 |
Hepatobiliary disorders | ||||||||
Hepatobiliary disorders | 8/1012 (0.8%) | 8 | 16/1044 (1.5%) | 16 | 16/1068 (1.5%) | 16 | 17/1079 (1.6%) | 18 |
Immune system disorders | ||||||||
Immune system disorders | 2/1012 (0.2%) | 2 | 1/1044 (0.1%) | 1 | 2/1068 (0.2%) | 2 | 2/1079 (0.2%) | 2 |
Infections and infestations | ||||||||
Infections and infestations | 90/1012 (8.9%) | 109 | 102/1044 (9.8%) | 139 | 103/1068 (9.6%) | 144 | 99/1079 (9.2%) | 127 |
Injury, poisoning and procedural complications | ||||||||
Injury, poisoning and procedural complications | 76/1012 (7.5%) | 90 | 62/1044 (5.9%) | 72 | 74/1068 (6.9%) | 90 | 66/1079 (6.1%) | 84 |
Investigations | ||||||||
Investigations | 14/1012 (1.4%) | 14 | 19/1044 (1.8%) | 20 | 13/1068 (1.2%) | 15 | 12/1079 (1.1%) | 12 |
Metabolism and nutrition disorders | ||||||||
Metabolism and nutrition disorders | 21/1012 (2.1%) | 22 | 16/1044 (1.5%) | 18 | 13/1068 (1.2%) | 13 | 23/1079 (2.1%) | 25 |
Musculoskeletal and connective tissue disorders | ||||||||
Musculoskeletal and connective tissue disorders | 66/1012 (6.5%) | 77 | 74/1044 (7.1%) | 91 | 71/1068 (6.6%) | 85 | 85/1079 (7.9%) | 101 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 80/1012 (7.9%) | 103 | 88/1044 (8.4%) | 111 | 83/1068 (7.8%) | 100 | 92/1079 (8.5%) | 112 |
Nervous system disorders | ||||||||
Nervous system disorders | 66/1012 (6.5%) | 73 | 74/1044 (7.1%) | 93 | 72/1068 (6.7%) | 87 | 73/1079 (6.8%) | 86 |
Psychiatric disorders | ||||||||
Psychiatric disorders | 4/1012 (0.4%) | 4 | 5/1044 (0.5%) | 5 | 5/1068 (0.5%) | 5 | 9/1079 (0.8%) | 11 |
Renal and urinary disorders | ||||||||
Renal and urinary disorders | 19/1012 (1.9%) | 20 | 25/1044 (2.4%) | 26 | 24/1068 (2.2%) | 25 | 25/1079 (2.3%) | 29 |
Reproductive system and breast disorders | ||||||||
Reproductive system and breast disorders | 9/1012 (0.9%) | 11 | 8/1044 (0.8%) | 8 | 12/1068 (1.1%) | 13 | 11/1079 (1%) | 11 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Respioratory, thoracic and mediastinal disorders | 44/1012 (4.3%) | 59 | 43/1044 (4.1%) | 52 | 37/1068 (3.5%) | 50 | 46/1079 (4.3%) | 51 |
Skin and subcutaneous tissue disorders | ||||||||
Skin and subcutaneous tissue disorders | 1/1012 (0.1%) | 1 | 6/1044 (0.6%) | 7 | 3/1068 (0.3%) | 3 | 5/1079 (0.5%) | 5 |
Surgical and medical procedures | ||||||||
Surgical and medical procedures | 32/1012 (3.2%) | 32 | 29/1044 (2.8%) | 31 | 27/1068 (2.5%) | 30 | 32/1079 (3%) | 32 |
Vascular disorders | ||||||||
Vascular disorders | 41/1012 (4.1%) | 45 | 40/1044 (3.8%) | 42 | 42/1068 (3.9%) | 45 | 42/1079 (3.9%) | 46 |
Other (Not Including Serious) Adverse Events |
||||||||
Placebo/Control | Lutein/Zeaxanthin | DHA/EPA | Lutein/Zeaxanthin + DHA/EPA | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 717/1012 (70.8%) | 791/1044 (75.8%) | 759/1068 (71.1%) | 791/1079 (73.3%) | ||||
Eye disorders | ||||||||
Dry eye | 55/1012 (5.4%) | 62 | 39/1044 (3.7%) | 40 | 64/1068 (6%) | 70 | 62/1079 (5.7%) | 70 |
Eye disorder | 67/1012 (6.6%) | 100 | 67/1044 (6.4%) | 96 | 62/1068 (5.8%) | 98 | 82/1079 (7.6%) | 152 |
Visual disturbance | 88/1012 (8.7%) | 118 | 110/1044 (10.5%) | 139 | 84/1068 (7.9%) | 116 | 88/1079 (8.2%) | 119 |
Vitreous disorder | 133/1012 (13.1%) | 208 | 154/1044 (14.8%) | 213 | 165/1068 (15.4%) | 228 | 162/1079 (15%) | 208 |
Gastrointestinal disorders | ||||||||
Change in bowel habit | 57/1012 (5.6%) | 69 | 67/1044 (6.4%) | 77 | 48/1068 (4.5%) | 58 | 57/1079 (5.3%) | 60 |
Infections and infestations | ||||||||
Bronchitis | 62/1012 (6.1%) | 72 | 69/1044 (6.6%) | 83 | 57/1068 (5.3%) | 80 | 56/1079 (5.2%) | 66 |
Upper respiratory tract infection | 139/1012 (13.7%) | 175 | 150/1044 (14.4%) | 190 | 139/1068 (13%) | 179 | 138/1079 (12.8%) | 173 |
Urinary tract infection | 57/1012 (5.6%) | 82 | 75/1044 (7.2%) | 103 | 71/1068 (6.6%) | 108 | 73/1079 (6.8%) | 96 |
Vascular disorders | ||||||||
Hypertension | 59/1012 (5.8%) | 66 | 60/1044 (5.7%) | 62 | 69/1068 (6.5%) | 72 | 73/1079 (6.8%) | 73 |
Limitations/Caveats
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.
Results Point of Contact
Name/Title | Traci Clemons, PhD |
---|---|
Organization | The EMMES Corporation |
Phone | 301-251-1161 ext 212 |
tclemons@emmes.com |
- NEI-120
- N01-EY-5-0007
- HHS-N-260-2005-00007-C
- CC-070025
- 07-EI-0025
- NCT00409513