Age-Related Eye Disease Study 2 (AREDS2)

Sponsor
National Eye Institute (NEI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00345176
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), Office of Dietary Supplements (ODS) (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH)
4,203
Enrollment
91
Locations
4
Arms
73
Duration (Months)
46.2
Patients Per Site
0.6
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
  • Dietary Supplement: Lutein/zeaxanthin
  • Dietary Supplement: DHA/EPA
  • Drug: Lutein/zeaxanthin and DHA/EPA
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:
  1. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function

  2. Outcome is measured with a battery of tests administered over the telephone at baseline, and at years 2 and 4 of the study.

  3. Primary outcome is the change in the composite score for the results of the cognitive function testing from baseline over time.

  4. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease

  1. Primary measure of cardiovascular morbidity and mortality
  1. Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
  1. Primary outcome is the development of peripheral drusen, geographic atrophy, reticular pigmentary changes, and pseudoreticular drusen.
  1. Association of genotype polymorphisms with age-related macular degeneration and cataract
  1. Whole genome sequencing will be completed. Evaluation of association genetic associations with disease will be conducted using AREDS controls.
  1. Association of genotype polymorphisms with progression of age-related macular degeneration
  1. 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.
  1. 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.

  2. 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

Study Type:
Interventional
Actual Enrollment :
4203 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Age-Related Eye Disease Study 2 (AREDS2): A Multi-center, Randomized Trial of Lutein, Zeaxanthin and Omega-3 Long-Chain Polyunsaturated Fatty Acids (Docosahexaenoic Acid [DHA] and Eicosapentaenoic Acid [EPA]) in Age-Related Macular Degeneration
Study Start Date :
Sep 1, 2006
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Oct 1, 2012

Arms and Interventions

ArmIntervention/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:
  • docosahexaenoic acid; eicosapentaenoic acid
  • 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

    1. 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

    1. Progression to Moderate Vision Loss [5 years of follow-up]

      Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization

    2. Adverse Events [5 years of follow-up]

      Safety outcomes included serious adverse events and mortality.

    3. 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

    1. Incident Cardiovascular Disease [5 years of follow-up]

      Effects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease

    2. 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

    3. 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

    4. Genetics for the Association of AMD and Cataract [5 years of follow-up]

    5. Genetics for the Progression of AMD and Cataract [5 years of follow-up]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294
    2Jones Eye Institute - UAMSLittle RockArkansasUnited States72205
    3Retina-Vitreous Associates Medical GroupBeverly HillsCaliforniaUnited States90211
    4Shiley Eye Center - UCSDLa JollaCaliforniaUnited States92093
    5Loma Linda UniversityLoma LindaCaliforniaUnited States92354
    6Doheny Eye InstituteLos AngelesCaliforniaUnited States90033
    7Jules Stein Eye InstituteLos AngelesCaliforniaUnited States90095
    8VA Northern California Health Care SystemMartinezCaliforniaUnited States94553
    9Southern California Desert Retina Consultants, MCPalm SpringsCaliforniaUnited States92262
    10University of California, DavisSacramentoCaliforniaUnited States95817
    11West Coast Retina Medical Group, IncSan FranciscoCaliforniaUnited States94107
    12Pacific Eye AssociatesSan FranciscoCaliforniaUnited States94115
    13Colorado Retina AssociatesDenverColoradoUnited States80218
    14Eldorado Retina Associates, PCLouisvilleColoradoUnited States80027
    15Yale University Eye CenterNew HavenConnecticutUnited States06510
    16Retina Group of FloridaFt. LauderdaleFloridaUnited States33334
    17University of FloridaJacksonvilleFloridaUnited States32209
    18Bascom Palmer Eye InstituteMiamiFloridaUnited States33136
    19Sarasota Retina InstituteSarasotaFloridaUnited States34239
    20Center for Retina and Macular DiseaseWinter HavenFloridaUnited States33880
    21Emory University Eye CenterAtlantaGeorgiaUnited States30322
    22Georgia Retina, PCDecaturGeorgiaUnited States30030
    23Northwestern UniversityChicagoIllinoisUnited States60611
    24The University of IllinoisChicagoIllinoisUnited States60612
    25NorthShore University HealthSystemsGlenviewIllinoisUnited States60026
    26Ingalls Memorial HospitalHarveyIllinoisUnited States60426
    27University of IowaIowa CityIowaUnited States52242
    28Retina Associates of KentuckyLexingtonKentuckyUnited States40509
    29Paducah Retinal CenterPaducahKentuckyUnited States42001
    30Elman Retina GroupBaltimoreMarylandUnited States21237
    31Wilmer Eye Institute, Johns Hopkins HospitalBaltimoreMarylandUnited States21287
    32National Eye InstituteBethesdaMarylandUnited States20892
    33The Retina Group of WashingtonChevy ChaseMarylandUnited States20815
    34Massachusetts Eye and Ear InfirmaryBostonMassachusettsUnited States02114
    35Ophthalmic Consultants of BostonBostonMassachusettsUnited States02114
    36Kresge Eye InstituteDetroitMichiganUnited States48201
    37Henry Ford Health System - Eye Care ServicesDetroitMichiganUnited States48202
    38Vision Research FoundationGrand RapidsMichiganUnited States49546
    39Vision Research FoundationRoyal OakMichiganUnited States48073
    40Vision Research FoundationTraverse CityMichiganUnited States49686
    41Mayo ClinicRochesterMinnesotaUnited States55905
    42University Health Care - Mason Eye InstituteColumbiaMissouriUnited States65212
    43Eye Foundation of Kansas CityKansas CityMissouriUnited States64108
    44Mid-America Retina Consultants, PAKansas CityMissouriUnited States64111
    45The Retina InstituteSt LouisMissouriUnited States63110
    46Washington University School of MedicineSt. LouisMissouriUnited States63110
    47Delaware Valley Retina AssociatesLawrencevilleNew JerseyUnited States08648
    48UMDNJNewarkNew JerseyUnited States07103
    49Ophthalmic Consultants of Long IslandLynbrookNew YorkUnited States11563
    50New York Eye and Ear InfirmaryNew YorkNew YorkUnited States10003
    51Manhattan Eye, Ear and Throat HospitalNew YorkNew YorkUnited States10021
    52University of Rochester Eye InstituteRochesterNew YorkUnited States14642
    53Retina Consultants, PLLCSlingerlandsNew YorkUnited States12159
    54The Research Foundation of SUNY/Stony BrookStony BrookNew YorkUnited States11794
    55Western Carolina Retinal AssociatesAshevilleNorth CarolinaUnited States28803
    56UNC Department of OphthalmologyChapel HillNorth CarolinaUnited States27599
    57Charlotte Eye Ear Nose and Throat AssociatesCharlotteNorth CarolinaUnited States28210
    58Duke UniversityDurhamNorth CarolinaUnited States27710
    59Wake Forest University Eye CenterWinston-SalemNorth CarolinaUnited States27157
    60Case Western Reserve UniversityClevelandOhioUnited States44106
    61Retina Associates of ClevelandClevelandOhioUnited States44122
    62Ohio State UniversityColumbusOhioUnited States43210
    63Retina Associates of ClevelandMiddleburg HeightsOhioUnited States44130
    64Retina Associates of ClevelandYoungstownOhioUnited States44505
    65Dean McGee Eye InstituteOklahoma CityOklahomaUnited States73104
    66Devers Eye InstitutePortlandOregonUnited States97210
    67Retina Northwest, PCPortlandOregonUnited States97210
    68Pennsylvania Retina Specialists, PCCamp HillPennsylvaniaUnited States17011
    69Penn State M.S. Hershey Medical CenterHersheyPennsylvaniaUnited States17033
    70Scheie Eye InstitutePhiladelphiaPennsylvaniaUnited States19104
    71Wills Eye Hospital/Mid Atlantic RetinaPhiladelphiaPennsylvaniaUnited States19107
    72Retina Vitreous ConsultantsPittsburghPennsylvaniaUnited States15213
    73University of Pittsburgh Medical CenterPittsburghPennsylvaniaUnited States15213
    74Palmetto Retina CenterColumbiaSouth CarolinaUnited States29204
    75Carolina Retina CenterColumbiaSouth CarolinaUnited States29223
    76Southeastern Retina Associates, PCKnoxvilleTennesseeUnited States37909
    77University of TennesseeMemphisTennesseeUnited States38163
    78Vanderbilt Eye InstituteNashvilleTennesseeUnited States37232
    79Texas Retina AssociatesArlingtonTexasUnited States76012
    80Texas Retina AssociatesDallasTexasUnited States75231
    81UT Southwestern Medical CenterDallasTexasUnited States75390
    82Baylor College of MedicineHoustonTexasUnited States77030
    83Retina Consultants of HoustonHoustonTexasUnited States77030
    84Texas Retina AssociatesLubbockTexasUnited States79424
    85Scott and White Memorial HospitalTempleTexasUnited States76508
    86John Moran Eye CenterSalt Lake CityUtahUnited States84132
    87Fletcher Allen Health CareBurlingtonVermontUnited States05401
    88The Retina Group of WashingtonFairfaxVirginiaUnited States22031
    89Retina Center NorthwestSilverdaleWashingtonUnited States98383
    90University of WisconsinMadisonWisconsinUnited States53705
    91The Medical College of WisconsinMilwaukeeWisconsinUnited States53226

    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.
    Responsible Party:
    National Eye Institute (NEI)
    ClinicalTrials.gov Identifier:
    NCT00345176
    Other Study ID Numbers:
    • NEI-120
    • N01-EY-5-0007
    • HHS-N-260-2005-00007-C
    • CC-070025
    • 07-EI-0025
    • NCT00409513
    First Posted:
    Jun 27, 2006
    Last Update Posted:
    May 5, 2015
    Last Verified:
    Apr 1, 2015

    Study Results

    Participant Flow

    Recruitment DetailsBetween October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites.
    Pre-assignment DetailPrior 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 TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (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
    STARTED1012104410681079
    COMPLETED1007103810621069
    NOT COMPLETED56610

    Baseline Characteristics

    Arm/Group TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPATotal
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (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 Participants10121044106810794203
    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

    1. Primary Outcome
    TitleDevelopment of Advanced AMD in People at Moderate to High Risk for Progression.
    DescriptionDefined 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 Frame5 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 TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (10mg)/zeaxanthin (2 mg)DHA (350 mg)/EPA (650 mg)lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants1007103810621069
    Measure Eyes1691170917491742
    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 Hypothesisp-Value<0.013
    CommentsAdjusted for 3 treatment versus placebo comparisons and interim analyses
    MethodRegression, Cox
    CommentsAdjusted for baseline AMD status
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.90
    Confidence Interval (2-Sided) 98.7%
    0.76 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation CommentsThe 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 Hypothesisp-Value<0.013
    CommentsAdjusted for multiple comparisons
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.97
    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 Hypothesisp-Value<0.013
    Comments
    MethodRegression, Cox
    CommentsAdjusted for multiple comparisons
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.89
    Confidence Interval (2-Sided) 98.7%
    0.75 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitleProgression to Moderate Vision Loss
    DescriptionLoss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (10mg)/zeaxanthin (2 mg)DHA (350 mg)/EPA (650 mg)lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants1007103810621069
    Measure Eyes1630166016941672
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.95
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.96
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.94
    Confidence Interval (2-Sided) 95%
    0.83 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    TitleAdverse Events
    DescriptionSafety outcomes included serious adverse events and mortality.
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    Number of deaths in 5 years
    Arm/Group TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (10mg)/zeaxanthin (2 mg)DHA (350 mg)/EPA (650 mg)lutein (10 mg)/zeaxanthin (2 mg) + DHA (350 mg)/EPA (650 mg)
    Measure Participants1012104410681079
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.04
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.13
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.23
    Confidence Interval (2-Sided) 95%
    0.92 to 1.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    TitleProgression to Cataract Surgery
    DescriptionThe 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 Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    Includes participants who were phakic in at least 1 eye at baseline
    Arm/Group TitleNo Lutein/ZeaxanthinLutein/Zeaxanthin
    Arm/Group DescriptionLutein main effect - includes participants who did not receive Lutein/ZeaxanthinLutein main effect - includes all participants who received Lutein/Zeaxanthin
    Measure Participants15771578
    Measure Eyes30223005
    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 Hypothesisp-Value<0.05
    Comments
    MethodRegression, Cox
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.96
    Confidence Interval (2-Sided) 95%
    0.84 to 1.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Other Pre-specified Outcome
    TitleIncident Cardiovascular Disease
    DescriptionEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on cardiovascular disease
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    6. Other Pre-specified Outcome
    TitleCognition as Measured by a Telephone Battery
    DescriptionEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin, zinc, and beta-carotene on cognitive function
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    7. Other Pre-specified Outcome
    TitlePrevalence of Peripheral Changes as Measured Using OPTOS Imaging
    DescriptionEffects of oral supplementation of omega-3 fatty acids, lutein/zeaxanthin on the peripheral retina
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    8. Other Pre-specified Outcome
    TitleGenetics for the Association of AMD and Cataract
    Description
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    9. Other Pre-specified Outcome
    TitleGenetics for the Progression of AMD and Cataract
    Description
    Time Frame5 years of follow-up

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame5 years
    Adverse Event Reporting Description Adverse events reported by System Organ Class
    Arm/Group TitlePlacebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Arm/Group DescriptionConsidered control because all participants received the AREDS formulationlutein (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/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total/ (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total479/1012 (47.3%) 484/1044 (46.4%) 505/1068 (47.3%) 519/1079 (48.1%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders12/1012 (1.2%) 1411/1044 (1.1%) 119/1068 (0.8%) 107/1079 (0.6%) 7
    Cardiac disorders
    Cardiac Disorders96/1012 (9.5%) 122110/1044 (10.5%) 138119/1068 (11.1%) 144103/1079 (9.5%) 133
    Congenital, familial and genetic disorders
    Congenital, familian and genetic disorders3/1012 (0.3%) 31/1044 (0.1%) 10/1068 (0%) 00/1079 (0%) 0
    Ear and labyrinth disorders
    Ear and labyrinth disorders7/1012 (0.7%) 73/1044 (0.3%) 34/1068 (0.4%) 41/1079 (0.1%) 1
    Endocrine disorders
    Endocrine disorders2/1012 (0.2%) 23/1044 (0.3%) 33/1068 (0.3%) 30/1079 (0%) 0
    Eye disorders
    Eye disorders3/1012 (0.3%) 311/1044 (1.1%) 134/1068 (0.4%) 60/1079 (0%) 0
    Gastrointestinal disorders
    Gastrointestinal disorders76/1012 (7.5%) 10169/1044 (6.6%) 8158/1068 (5.4%) 7261/1079 (5.7%) 71
    General disorders
    General disorders and administration site conditions54/1012 (5.3%) 6050/1044 (4.8%) 5451/1068 (4.8%) 5846/1079 (4.3%) 50
    Hepatobiliary disorders
    Hepatobiliary disorders8/1012 (0.8%) 816/1044 (1.5%) 1616/1068 (1.5%) 1617/1079 (1.6%) 18
    Immune system disorders
    Immune system disorders2/1012 (0.2%) 21/1044 (0.1%) 12/1068 (0.2%) 22/1079 (0.2%) 2
    Infections and infestations
    Infections and infestations90/1012 (8.9%) 109102/1044 (9.8%) 139103/1068 (9.6%) 14499/1079 (9.2%) 127
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications76/1012 (7.5%) 9062/1044 (5.9%) 7274/1068 (6.9%) 9066/1079 (6.1%) 84
    Investigations
    Investigations14/1012 (1.4%) 1419/1044 (1.8%) 2013/1068 (1.2%) 1512/1079 (1.1%) 12
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders21/1012 (2.1%) 2216/1044 (1.5%) 1813/1068 (1.2%) 1323/1079 (2.1%) 25
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders66/1012 (6.5%) 7774/1044 (7.1%) 9171/1068 (6.6%) 8585/1079 (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%) 10388/1044 (8.4%) 11183/1068 (7.8%) 10092/1079 (8.5%) 112
    Nervous system disorders
    Nervous system disorders66/1012 (6.5%) 7374/1044 (7.1%) 9372/1068 (6.7%) 8773/1079 (6.8%) 86
    Psychiatric disorders
    Psychiatric disorders4/1012 (0.4%) 45/1044 (0.5%) 55/1068 (0.5%) 59/1079 (0.8%) 11
    Renal and urinary disorders
    Renal and urinary disorders19/1012 (1.9%) 2025/1044 (2.4%) 2624/1068 (2.2%) 2525/1079 (2.3%) 29
    Reproductive system and breast disorders
    Reproductive system and breast disorders9/1012 (0.9%) 118/1044 (0.8%) 812/1068 (1.1%) 1311/1079 (1%) 11
    Respiratory, thoracic and mediastinal disorders
    Respioratory, thoracic and mediastinal disorders44/1012 (4.3%) 5943/1044 (4.1%) 5237/1068 (3.5%) 5046/1079 (4.3%) 51
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders1/1012 (0.1%) 16/1044 (0.6%) 73/1068 (0.3%) 35/1079 (0.5%) 5
    Surgical and medical procedures
    Surgical and medical procedures32/1012 (3.2%) 3229/1044 (2.8%) 3127/1068 (2.5%) 3032/1079 (3%) 32
    Vascular disorders
    Vascular disorders41/1012 (4.1%) 4540/1044 (3.8%) 4242/1068 (3.9%) 4542/1079 (3.9%) 46
    Other (Not Including Serious) Adverse Events
    Placebo/ControlLutein/ZeaxanthinDHA/EPALutein/Zeaxanthin + DHA/EPA
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total717/1012 (70.8%) 791/1044 (75.8%) 759/1068 (71.1%) 791/1079 (73.3%)
    Eye disorders
    Dry eye55/1012 (5.4%) 6239/1044 (3.7%) 4064/1068 (6%) 7062/1079 (5.7%) 70
    Eye disorder67/1012 (6.6%) 10067/1044 (6.4%) 9662/1068 (5.8%) 9882/1079 (7.6%) 152
    Visual disturbance88/1012 (8.7%) 118110/1044 (10.5%) 13984/1068 (7.9%) 11688/1079 (8.2%) 119
    Vitreous disorder133/1012 (13.1%) 208154/1044 (14.8%) 213165/1068 (15.4%) 228162/1079 (15%) 208
    Gastrointestinal disorders
    Change in bowel habit57/1012 (5.6%) 6967/1044 (6.4%) 7748/1068 (4.5%) 5857/1079 (5.3%) 60
    Infections and infestations
    Bronchitis62/1012 (6.1%) 7269/1044 (6.6%) 8357/1068 (5.3%) 8056/1079 (5.2%) 66
    Upper respiratory tract infection139/1012 (13.7%) 175150/1044 (14.4%) 190139/1068 (13%) 179138/1079 (12.8%) 173
    Urinary tract infection57/1012 (5.6%) 8275/1044 (7.2%) 10371/1068 (6.6%) 10873/1079 (6.8%) 96
    Vascular disorders
    Hypertension59/1012 (5.8%) 6660/1044 (5.7%) 6269/1068 (6.5%) 7273/1079 (6.8%) 73

    Limitations/Caveats

    [Not Specified]

    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/TitleTraci Clemons, PhD
    OrganizationThe EMMES Corporation
    Phone301-251-1161 ext 212
    Emailtclemons@emmes.com
    Responsible Party:
    National Eye Institute (NEI)
    ClinicalTrials.gov Identifier:
    NCT00345176
    Other Study ID Numbers:
    • NEI-120
    • N01-EY-5-0007
    • HHS-N-260-2005-00007-C
    • CC-070025
    • 07-EI-0025
    • NCT00409513
    First Posted:
    Jun 27, 2006
    Last Update Posted:
    May 5, 2015
    Last Verified:
    Apr 1, 2015