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Age-Related Eye Disease Study 2 (AREDS2) (AREDS2)

This study has been completed.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Office of Dietary Supplements (ODS)
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
National Eye Institute (NEI)
ClinicalTrials.gov Identifier:
NCT00345176
First received: June 14, 2006
Last updated: April 13, 2015
Last verified: April 2015
Results First Received: November 1, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Age-related Macular Degeneration
Cataract
Interventions: Dietary Supplement: Lutein/zeaxanthin
Dietary Supplement: DHA/EPA
Drug: Lutein/zeaxanthin and DHA/EPA

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between October 2006 and September 2008 a total of 4,203 participants aged 50 - 85 years were randomized at 82 clinical sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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)

Participant Flow:   Overall Study
    Placebo/Control   Lutein/Zeaxanthin   DHA/EPA   Lutein/Zeaxanthin + DHA/EPA
STARTED   1012   1044   1068   1079 
COMPLETED   1007   1038   1062   1069 
NOT COMPLETED   5   6   6   10 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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)
Total Total of all reporting groups

Baseline Measures
   Placebo/Control   Lutein/Zeaxanthin   DHA/EPA   Lutein/Zeaxanthin + DHA/EPA   Total 
Overall Participants Analyzed 
[Units: Participants]
 1012   1044   1068   1079   4203 
Age 
[Units: Participants]
Median (Inter-Quartile Range)
 74 
 (68 to 79) 
 74 
 (68 to 79) 
 74 
 (68 to 79) 
 75 
 (68 to 79) 
 74 
 (68 to 79) 
Gender 
[Units: Participants]
         
Female   548   596   603   641   2388 
Male   464   448   465   438   1815 


  Outcome Measures
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1.  Primary:   Development of Advanced AMD in People at Moderate to High Risk for Progression.   [ Time Frame: 5 years of follow-up ]

Measure Type Primary
Measure Title Development of Advanced AMD in People at Moderate to High Risk for Progression.
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat. Participants lost to follow-up during the course of the study were censored at the time of last contact.

Reporting Groups
  Description
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)

Measured Values
   Placebo/Control   Lutein/Zeaxanthin   DHA/EPA   Lutein/Zeaxanthin + DHA/EPA 
Participants Analyzed 
[Units: Participants]
 1007   1038   1062   1069 
Units Analyzed (Eyes) 
[Units: Eyes]
 1691   1709   1749   1742 
Development of Advanced AMD in People at Moderate to High Risk for Progression. 
[Units: Eyes]
 493   468   507   472 


Statistical Analysis 1 for Development of Advanced AMD in People at Moderate to High Risk for Progression.
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin
Method [2] Regression, Cox
P Value [3] <0.013
Hazard Ratio (HR) [4] 0.90
98.7% Confidence Interval 0.76 to 1.07
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Each of the 3 active arms was compared to the placebo/control arm.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for baseline AMD status
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for 3 treatment versus placebo comparisons and interim analyses
[4] Other relevant estimation information:
  The reference group is placebo.

Statistical Analysis 2 for Development of Advanced AMD in People at Moderate to High Risk for Progression.
Groups [1] Placebo/Control vs. DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.013
Hazard Ratio (HR) [4] 0.97
98.7% Confidence Interval 0.82 to 1.16
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted for multiple comparisons
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Development of Advanced AMD in People at Moderate to High Risk for Progression.
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin + DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.013
Hazard Ratio (HR) [4] 0.89
98.7% Confidence Interval 0.75 to 1.06
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted for multiple comparisons
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Progression to Moderate Vision Loss   [ Time Frame: 5 years of follow-up ]

Measure Type Secondary
Measure Title Progression to Moderate Vision Loss
Measure Description Loss defined as >/= 3 lines of letters from baseline or treatment for choroidal neovascularization
Time Frame 5 years of follow-up  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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)

Measured Values
   Placebo/Control   Lutein/Zeaxanthin   DHA/EPA   Lutein/Zeaxanthin + DHA/EPA 
Participants Analyzed 
[Units: Participants]
 1007   1038   1062   1069 
Units Analyzed (Eyes) 
[Units: Eyes]
 1630   1660   1694   1672 
Progression to Moderate Vision Loss 
[Units: Eyes]
 515   509   519   506 


Statistical Analysis 1 for Progression to Moderate Vision Loss
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 0.95
95% Confidence Interval 0.84 to 1.08
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Progression to Moderate Vision Loss
Groups [1] Placebo/Control vs. DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 0.96
95% Confidence Interval 0.84 to 1.09
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Progression to Moderate Vision Loss
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin + DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 0.94
95% Confidence Interval 0.83 to 1.07
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Adverse Events   [ Time Frame: 5 years of follow-up ]

Measure Type Secondary
Measure Title Adverse Events
Measure Description Safety outcomes included serious adverse events and mortality.
Time Frame 5 years of follow-up  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of deaths in 5 years

Reporting Groups
  Description
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)

Measured Values
   Placebo/Control   Lutein/Zeaxanthin   DHA/EPA   Lutein/Zeaxanthin + DHA/EPA 
Participants Analyzed 
[Units: Participants]
 1012   1044   1068   1079 
Adverse Events 
[Units: Participants]
       
Mortality   81   87   96   104 
Serious Adverse Events   479   484   505   519 


Statistical Analysis 1 for Adverse Events
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 1.04
95% Confidence Interval 0.77 to 1.40
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison of Lutein/Zeaxantin versus Control for mortality
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Adverse Events
Groups [1] Placebo/Control vs. DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 1.13
95% Confidence Interval 0.84 to 1.52
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison of DHA/EPA versus Placebo for mortality
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Adverse Events
Groups [1] Placebo/Control vs. Lutein/Zeaxanthin + DHA/EPA
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 1.23
95% Confidence Interval 0.92 to 1.65
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Comparison of Lutein/Zeaxanthin + DHA/EPA versus Placebo for Mortality
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Progression to Cataract Surgery   [ Time Frame: 5 years of follow-up ]

Measure Type Secondary
Measure Title Progression to Cataract Surgery
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Includes participants who were phakic in at least 1 eye at baseline

Reporting Groups
  Description
No Lutein/Zeaxanthin Lutein main effect - includes participants who did not receive Lutein/Zeaxanthin
Lutein/Zeaxanthin Lutein main effect - includes all participants who received Lutein/Zeaxanthin

Measured Values
   No Lutein/Zeaxanthin   Lutein/Zeaxanthin 
Participants Analyzed 
[Units: Participants]
 1577   1578 
Units Analyzed (Eyes) 
[Units: Eyes]
 3022   3005 
Progression to Cataract Surgery 
[Units: Eyes]
 708   681 


Statistical Analysis 1 for Progression to Cataract Surgery
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] <0.05
Hazard Ratio (HR) [4] 0.96
95% Confidence Interval 0.84 to 1.10
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



5.  Other Pre-specified:   Incident Cardiovascular Disease   [ Time Frame: 5 years of follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Other Pre-specified:   Cognition as Measured by a Telephone Battery   [ Time Frame: 5 years of follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Other Pre-specified:   Prevalence of Peripheral Changes as Measured Using OPTOS Imaging   [ Time Frame: 5 years of follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Other Pre-specified:   Genetics for the Association of AMD and Cataract   [ Time Frame: 5 years of follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

9.  Other Pre-specified:   Genetics for the Progression of AMD and Cataract   [ Time Frame: 5 years of follow-up ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information