Trial Outcomes & Findings for Age-Related Eye Disease Study 2 (AREDS2) (NCT NCT00345176)
NCT ID: NCT00345176
Last Updated: 2015-05-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
4203 participants
Primary outcome timeframe
5 years of follow-up
Results posted on
2015-05-05
Participant Flow
Between October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites.
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.
Participant milestones
| Measure |
Placebo/Control
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
1012
|
1044
|
1068
|
1079
|
|
Overall Study
COMPLETED
|
1007
|
1038
|
1062
|
1069
|
|
Overall Study
NOT COMPLETED
|
5
|
6
|
6
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Age-Related Eye Disease Study 2 (AREDS2)
Baseline characteristics by cohort
| Measure |
Placebo/Control
n=1012 Participants
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1044 Participants
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1068 Participants
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1079 Participants
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
Total
n=4203 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
74 Participants
n=93 Participants
|
74 Participants
n=4 Participants
|
74 Participants
n=27 Participants
|
75 Participants
n=483 Participants
|
74 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
548 Participants
n=93 Participants
|
596 Participants
n=4 Participants
|
603 Participants
n=27 Participants
|
641 Participants
n=483 Participants
|
2388 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
464 Participants
n=93 Participants
|
448 Participants
n=4 Participants
|
465 Participants
n=27 Participants
|
438 Participants
n=483 Participants
|
1815 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: 5 years of follow-upPopulation: Intention to Treat. Participants lost to follow-up during the course of the study were censored at the time of last contact.
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.
Outcome measures
| Measure |
Placebo/Control
n=1691 Eyes
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1709 Eyes
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1749 Eyes
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1742 Eyes
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Development of Advanced AMD in People at Moderate to High Risk for Progression.
|
493 Eyes
|
468 Eyes
|
507 Eyes
|
472 Eyes
|
SECONDARY outcome
Timeframe: 5 years of follow-upLoss defined as \>/= 3 lines of letters from baseline or treatment for choroidal neovascularization
Outcome measures
| Measure |
Placebo/Control
n=1630 Eyes
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1660 Eyes
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1694 Eyes
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1672 Eyes
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Progression to Moderate Vision Loss
|
515 Eyes
|
509 Eyes
|
519 Eyes
|
506 Eyes
|
SECONDARY outcome
Timeframe: 5 years of follow-upPopulation: Number of deaths in 5 years
Safety outcomes included serious adverse events and mortality.
Outcome measures
| Measure |
Placebo/Control
n=1012 Participants
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1044 Participants
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1068 Participants
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1079 Participants
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Adverse Events
Mortality
|
81 Participants
|
87 Participants
|
96 Participants
|
104 Participants
|
|
Adverse Events
Serious Adverse Events
|
479 Participants
|
484 Participants
|
505 Participants
|
519 Participants
|
SECONDARY outcome
Timeframe: 5 years of follow-upPopulation: Includes participants who were phakic in at least 1 eye at baseline
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.
Outcome measures
| Measure |
Placebo/Control
n=3022 Eyes
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=3005 Eyes
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Progression to Cataract Surgery
|
708 Eyes
|
681 Eyes
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 5 years of follow-upEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 5 years of follow-upEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 5 years of follow-upEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 5 years of follow-upOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 5 years of follow-upOutcome measures
Outcome data not reported
Adverse Events
Placebo/Control
Serious events: 479 serious events
Other events: 717 other events
Deaths: 0 deaths
Lutein/Zeaxanthin
Serious events: 484 serious events
Other events: 791 other events
Deaths: 0 deaths
DHA/EPA
Serious events: 505 serious events
Other events: 759 other events
Deaths: 0 deaths
Lutein/Zeaxanthin + DHA/EPA
Serious events: 519 serious events
Other events: 791 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo/Control
n=1012 participants at risk
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1044 participants at risk
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1068 participants at risk
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1079 participants at risk
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Cardiac disorders
Cardiac Disorders
|
9.5%
96/1012 • Number of events 122 • 5 years
Adverse events reported by System Organ Class
|
10.5%
110/1044 • Number of events 138 • 5 years
Adverse events reported by System Organ Class
|
11.1%
119/1068 • Number of events 144 • 5 years
Adverse events reported by System Organ Class
|
9.5%
103/1079 • Number of events 133 • 5 years
Adverse events reported by System Organ Class
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
7.5%
76/1012 • Number of events 101 • 5 years
Adverse events reported by System Organ Class
|
6.6%
69/1044 • Number of events 81 • 5 years
Adverse events reported by System Organ Class
|
5.4%
58/1068 • Number of events 72 • 5 years
Adverse events reported by System Organ Class
|
5.7%
61/1079 • Number of events 71 • 5 years
Adverse events reported by System Organ Class
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
1.2%
12/1012 • Number of events 14 • 5 years
Adverse events reported by System Organ Class
|
1.1%
11/1044 • Number of events 11 • 5 years
Adverse events reported by System Organ Class
|
0.84%
9/1068 • Number of events 10 • 5 years
Adverse events reported by System Organ Class
|
0.65%
7/1079 • Number of events 7 • 5 years
Adverse events reported by System Organ Class
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
0.69%
7/1012 • Number of events 7 • 5 years
Adverse events reported by System Organ Class
|
0.29%
3/1044 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
0.37%
4/1068 • Number of events 4 • 5 years
Adverse events reported by System Organ Class
|
0.09%
1/1079 • Number of events 1 • 5 years
Adverse events reported by System Organ Class
|
|
Congenital, familial and genetic disorders
Congenital, familian and genetic disorders
|
0.30%
3/1012 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
0.10%
1/1044 • Number of events 1 • 5 years
Adverse events reported by System Organ Class
|
0.00%
0/1068 • 5 years
Adverse events reported by System Organ Class
|
0.00%
0/1079 • 5 years
Adverse events reported by System Organ Class
|
|
Endocrine disorders
Endocrine disorders
|
0.20%
2/1012 • Number of events 2 • 5 years
Adverse events reported by System Organ Class
|
0.29%
3/1044 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
0.28%
3/1068 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
0.00%
0/1079 • 5 years
Adverse events reported by System Organ Class
|
|
Eye disorders
Eye disorders
|
0.30%
3/1012 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
1.1%
11/1044 • Number of events 13 • 5 years
Adverse events reported by System Organ Class
|
0.37%
4/1068 • Number of events 6 • 5 years
Adverse events reported by System Organ Class
|
0.00%
0/1079 • 5 years
Adverse events reported by System Organ Class
|
|
General disorders
General disorders and administration site conditions
|
5.3%
54/1012 • Number of events 60 • 5 years
Adverse events reported by System Organ Class
|
4.8%
50/1044 • Number of events 54 • 5 years
Adverse events reported by System Organ Class
|
4.8%
51/1068 • Number of events 58 • 5 years
Adverse events reported by System Organ Class
|
4.3%
46/1079 • Number of events 50 • 5 years
Adverse events reported by System Organ Class
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
0.79%
8/1012 • Number of events 8 • 5 years
Adverse events reported by System Organ Class
|
1.5%
16/1044 • Number of events 16 • 5 years
Adverse events reported by System Organ Class
|
1.5%
16/1068 • Number of events 16 • 5 years
Adverse events reported by System Organ Class
|
1.6%
17/1079 • Number of events 18 • 5 years
Adverse events reported by System Organ Class
|
|
Immune system disorders
Immune system disorders
|
0.20%
2/1012 • Number of events 2 • 5 years
Adverse events reported by System Organ Class
|
0.10%
1/1044 • Number of events 1 • 5 years
Adverse events reported by System Organ Class
|
0.19%
2/1068 • Number of events 2 • 5 years
Adverse events reported by System Organ Class
|
0.19%
2/1079 • Number of events 2 • 5 years
Adverse events reported by System Organ Class
|
|
Infections and infestations
Infections and infestations
|
8.9%
90/1012 • Number of events 109 • 5 years
Adverse events reported by System Organ Class
|
9.8%
102/1044 • Number of events 139 • 5 years
Adverse events reported by System Organ Class
|
9.6%
103/1068 • Number of events 144 • 5 years
Adverse events reported by System Organ Class
|
9.2%
99/1079 • Number of events 127 • 5 years
Adverse events reported by System Organ Class
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
7.5%
76/1012 • Number of events 90 • 5 years
Adverse events reported by System Organ Class
|
5.9%
62/1044 • Number of events 72 • 5 years
Adverse events reported by System Organ Class
|
6.9%
74/1068 • Number of events 90 • 5 years
Adverse events reported by System Organ Class
|
6.1%
66/1079 • Number of events 84 • 5 years
Adverse events reported by System Organ Class
|
|
Investigations
Investigations
|
1.4%
14/1012 • Number of events 14 • 5 years
Adverse events reported by System Organ Class
|
1.8%
19/1044 • Number of events 20 • 5 years
Adverse events reported by System Organ Class
|
1.2%
13/1068 • Number of events 15 • 5 years
Adverse events reported by System Organ Class
|
1.1%
12/1079 • Number of events 12 • 5 years
Adverse events reported by System Organ Class
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
2.1%
21/1012 • Number of events 22 • 5 years
Adverse events reported by System Organ Class
|
1.5%
16/1044 • Number of events 18 • 5 years
Adverse events reported by System Organ Class
|
1.2%
13/1068 • Number of events 13 • 5 years
Adverse events reported by System Organ Class
|
2.1%
23/1079 • Number of events 25 • 5 years
Adverse events reported by System Organ Class
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
6.5%
66/1012 • Number of events 77 • 5 years
Adverse events reported by System Organ Class
|
7.1%
74/1044 • Number of events 91 • 5 years
Adverse events reported by System Organ Class
|
6.6%
71/1068 • Number of events 85 • 5 years
Adverse events reported by System Organ Class
|
7.9%
85/1079 • Number of events 101 • 5 years
Adverse events reported by System Organ Class
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
7.9%
80/1012 • Number of events 103 • 5 years
Adverse events reported by System Organ Class
|
8.4%
88/1044 • Number of events 111 • 5 years
Adverse events reported by System Organ Class
|
7.8%
83/1068 • Number of events 100 • 5 years
Adverse events reported by System Organ Class
|
8.5%
92/1079 • Number of events 112 • 5 years
Adverse events reported by System Organ Class
|
|
Nervous system disorders
Nervous system disorders
|
6.5%
66/1012 • Number of events 73 • 5 years
Adverse events reported by System Organ Class
|
7.1%
74/1044 • Number of events 93 • 5 years
Adverse events reported by System Organ Class
|
6.7%
72/1068 • Number of events 87 • 5 years
Adverse events reported by System Organ Class
|
6.8%
73/1079 • Number of events 86 • 5 years
Adverse events reported by System Organ Class
|
|
Psychiatric disorders
Psychiatric disorders
|
0.40%
4/1012 • Number of events 4 • 5 years
Adverse events reported by System Organ Class
|
0.48%
5/1044 • Number of events 5 • 5 years
Adverse events reported by System Organ Class
|
0.47%
5/1068 • Number of events 5 • 5 years
Adverse events reported by System Organ Class
|
0.83%
9/1079 • Number of events 11 • 5 years
Adverse events reported by System Organ Class
|
|
Renal and urinary disorders
Renal and urinary disorders
|
1.9%
19/1012 • Number of events 20 • 5 years
Adverse events reported by System Organ Class
|
2.4%
25/1044 • Number of events 26 • 5 years
Adverse events reported by System Organ Class
|
2.2%
24/1068 • Number of events 25 • 5 years
Adverse events reported by System Organ Class
|
2.3%
25/1079 • Number of events 29 • 5 years
Adverse events reported by System Organ Class
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
0.89%
9/1012 • Number of events 11 • 5 years
Adverse events reported by System Organ Class
|
0.77%
8/1044 • Number of events 8 • 5 years
Adverse events reported by System Organ Class
|
1.1%
12/1068 • Number of events 13 • 5 years
Adverse events reported by System Organ Class
|
1.0%
11/1079 • Number of events 11 • 5 years
Adverse events reported by System Organ Class
|
|
Respiratory, thoracic and mediastinal disorders
Respioratory, thoracic and mediastinal disorders
|
4.3%
44/1012 • Number of events 59 • 5 years
Adverse events reported by System Organ Class
|
4.1%
43/1044 • Number of events 52 • 5 years
Adverse events reported by System Organ Class
|
3.5%
37/1068 • Number of events 50 • 5 years
Adverse events reported by System Organ Class
|
4.3%
46/1079 • Number of events 51 • 5 years
Adverse events reported by System Organ Class
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.10%
1/1012 • Number of events 1 • 5 years
Adverse events reported by System Organ Class
|
0.57%
6/1044 • Number of events 7 • 5 years
Adverse events reported by System Organ Class
|
0.28%
3/1068 • Number of events 3 • 5 years
Adverse events reported by System Organ Class
|
0.46%
5/1079 • Number of events 5 • 5 years
Adverse events reported by System Organ Class
|
|
Surgical and medical procedures
Surgical and medical procedures
|
3.2%
32/1012 • Number of events 32 • 5 years
Adverse events reported by System Organ Class
|
2.8%
29/1044 • Number of events 31 • 5 years
Adverse events reported by System Organ Class
|
2.5%
27/1068 • Number of events 30 • 5 years
Adverse events reported by System Organ Class
|
3.0%
32/1079 • Number of events 32 • 5 years
Adverse events reported by System Organ Class
|
|
Vascular disorders
Vascular disorders
|
4.1%
41/1012 • Number of events 45 • 5 years
Adverse events reported by System Organ Class
|
3.8%
40/1044 • Number of events 42 • 5 years
Adverse events reported by System Organ Class
|
3.9%
42/1068 • Number of events 45 • 5 years
Adverse events reported by System Organ Class
|
3.9%
42/1079 • Number of events 46 • 5 years
Adverse events reported by System Organ Class
|
Other adverse events
| Measure |
Placebo/Control
n=1012 participants at risk
Considered control because all participants received the AREDS formulation
|
Lutein/Zeaxanthin
n=1044 participants at risk
lutein (10mg)/zeaxanthin (2 mg)
|
DHA/EPA
n=1068 participants at risk
DHA (350 mg)/EPA (650 mg)
|
Lutein/Zeaxanthin + DHA/EPA
n=1079 participants at risk
lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
|
|---|---|---|---|---|
|
Eye disorders
Dry eye
|
5.4%
55/1012 • Number of events 62 • 5 years
Adverse events reported by System Organ Class
|
3.7%
39/1044 • Number of events 40 • 5 years
Adverse events reported by System Organ Class
|
6.0%
64/1068 • Number of events 70 • 5 years
Adverse events reported by System Organ Class
|
5.7%
62/1079 • Number of events 70 • 5 years
Adverse events reported by System Organ Class
|
|
Eye disorders
Eye disorder
|
6.6%
67/1012 • Number of events 100 • 5 years
Adverse events reported by System Organ Class
|
6.4%
67/1044 • Number of events 96 • 5 years
Adverse events reported by System Organ Class
|
5.8%
62/1068 • Number of events 98 • 5 years
Adverse events reported by System Organ Class
|
7.6%
82/1079 • Number of events 152 • 5 years
Adverse events reported by System Organ Class
|
|
Eye disorders
Visual disturbance
|
8.7%
88/1012 • Number of events 118 • 5 years
Adverse events reported by System Organ Class
|
10.5%
110/1044 • Number of events 139 • 5 years
Adverse events reported by System Organ Class
|
7.9%
84/1068 • Number of events 116 • 5 years
Adverse events reported by System Organ Class
|
8.2%
88/1079 • Number of events 119 • 5 years
Adverse events reported by System Organ Class
|
|
Eye disorders
Vitreous disorder
|
13.1%
133/1012 • Number of events 208 • 5 years
Adverse events reported by System Organ Class
|
14.8%
154/1044 • Number of events 213 • 5 years
Adverse events reported by System Organ Class
|
15.4%
165/1068 • Number of events 228 • 5 years
Adverse events reported by System Organ Class
|
15.0%
162/1079 • Number of events 208 • 5 years
Adverse events reported by System Organ Class
|
|
Gastrointestinal disorders
Change in bowel habit
|
5.6%
57/1012 • Number of events 69 • 5 years
Adverse events reported by System Organ Class
|
6.4%
67/1044 • Number of events 77 • 5 years
Adverse events reported by System Organ Class
|
4.5%
48/1068 • Number of events 58 • 5 years
Adverse events reported by System Organ Class
|
5.3%
57/1079 • Number of events 60 • 5 years
Adverse events reported by System Organ Class
|
|
Infections and infestations
Bronchitis
|
6.1%
62/1012 • Number of events 72 • 5 years
Adverse events reported by System Organ Class
|
6.6%
69/1044 • Number of events 83 • 5 years
Adverse events reported by System Organ Class
|
5.3%
57/1068 • Number of events 80 • 5 years
Adverse events reported by System Organ Class
|
5.2%
56/1079 • Number of events 66 • 5 years
Adverse events reported by System Organ Class
|
|
Infections and infestations
Upper respiratory tract infection
|
13.7%
139/1012 • Number of events 175 • 5 years
Adverse events reported by System Organ Class
|
14.4%
150/1044 • Number of events 190 • 5 years
Adverse events reported by System Organ Class
|
13.0%
139/1068 • Number of events 179 • 5 years
Adverse events reported by System Organ Class
|
12.8%
138/1079 • Number of events 173 • 5 years
Adverse events reported by System Organ Class
|
|
Infections and infestations
Urinary tract infection
|
5.6%
57/1012 • Number of events 82 • 5 years
Adverse events reported by System Organ Class
|
7.2%
75/1044 • Number of events 103 • 5 years
Adverse events reported by System Organ Class
|
6.6%
71/1068 • Number of events 108 • 5 years
Adverse events reported by System Organ Class
|
6.8%
73/1079 • Number of events 96 • 5 years
Adverse events reported by System Organ Class
|
|
Vascular disorders
Hypertension
|
5.8%
59/1012 • Number of events 66 • 5 years
Adverse events reported by System Organ Class
|
5.7%
60/1044 • Number of events 62 • 5 years
Adverse events reported by System Organ Class
|
6.5%
69/1068 • Number of events 72 • 5 years
Adverse events reported by System Organ Class
|
6.8%
73/1079 • Number of events 73 • 5 years
Adverse events reported by System Organ Class
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place