SEE: S0000B: Vitamin E and/or Selenium in Preventing Cataract and Age-Related Macular Degeneration in Men on SELECT SWOG-S0000

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00784225
• Collaborator: National Cancer Institute (NCI) (NIH), National Eye Institute (NEI) (NIH)
• Enrollment: 13,475
• Location: 1
• Arms: 4
• Duration (Months): 166
• Patients Per Site Per Month: 81.2

Study Details

Study Description

Brief Summary

RATIONALE: Aging may affect a person's vision. Vitamin E and/or selenium may help prevent cataracts or age-related macular degeneration in men receiving these drugs as part of a clinical trial for the prevention of prostate cancer.

PURPOSE: This clinical trial is studying vitamin E and/or selenium to see how well they work in preventing cataract and age-related macular degeneration in men enrolled on SELECT (SWOG-S0000).

Condition or Disease	Intervention/Treatment	Phase
Cataract; Macular Degeneration	Drug: selenium; Drug: vitamin E; Drug: vitamin E placebo; Drug: selenium placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To test whether vitamin E and/or selenium reduces the risk of visually significant age-related macular degeneration (AMD) in men enrolled on SELECT (SWOG-S0000).

• To test whether vitamin E and/or selenium reduces the risk of cataract in these participants.

Secondary

• To test whether vitamin E and/or selenium reduces the risk of advanced AMD in these participants.

• To test whether vitamin E and/or selenium reduces the risk of cataract surgery and subtypes in these participants.

OUTLINE: This is a multicenter study.

Data from medical records obtained from the participant's ophthalmologist or optometrist are reviewed. Information from these records is then used to confirm baseline reports of age-related macular degeneration (AMD) as well as 6-month and annual reports of new diagnoses of AMD and cataract (or cataract surgery) made since the start of this study. Detailed questionnaires are also obtained from the participant's ophthalmologist or optometrist to provide information about the reported AMD or cataract diagnosis (e.g., date of initial diagnosis; best-corrected visual acuity at the time of diagnosis; date when visual acuity was first noted to be 20/30 or worse [if different from the date of initial diagnosis]; pathological findings observed when AMD was first diagnosed [e.g., drusen, retinal pigment epithelial hypo/hyperpigmentation, geographic atrophy, retinal pigment epithelial detachment, subretinal neovascular membrane, or disciform scar]; pathological findings observed when visual acuity was first noted to be 20/30 or worse; date when exudative [wet] AMD was first noted; presence of other ocular abnormalities that could explain or contribute to visual loss; whether AMD or cataract, by itself, are significant enough to cause vision to be reduced to 20/30 or worse; whether laser treatment or photodynamic therapy was performed for AMD; date of cataract extraction; etiology of cataract [e.g., age-related, traumatic, congenital, inflammatory, or surgery- or steroid-induced]; and cataract type [e.g., nuclear, cortical, posterior subcapsular, or other]).

Study Design

• Study Type: Interventional
• Actual Enrollment: 13475 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: S0000B: Prevention of Cataract and Age-Related Macular Degeneration With Vitamin E and Selenium - SELECT Eye Endpoints (SEE)
• Study Start Date: Jul 1, 2004
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin E + selenium placebo vitamin E and selenium placebo daily for 7-12 years	Drug: vitamin E; 400 IU daily by mouth for 7-12 years; Other Names: alpha tocopherol ; Drug: selenium placebo; daily for 7-12 years; Other Names: placebo
Experimental: Selenium + vitamin E placebo selenium and vitamin E placebo daily for 7-12 years	Drug: selenium; 200 mcg daily for 7-12 years; Other Names: L-selenomethionine ; Drug: vitamin E placebo; daily for 7-12 years; Other Names: placebo ; Drug: selenium placebo; daily for 7-12 years; Other Names: placebo
Experimental: Vitamin E + selenium vitamin E and selenium placebo daily for 7-12 years	Drug: selenium; 200 mcg daily for 7-12 years; Other Names: L-selenomethionine ; Drug: vitamin E; 400 IU daily by mouth for 7-12 years; Other Names: alpha tocopherol
Placebo Comparator: Vitamin E placebo + selenium placebo vitamin E placebo and selenium placebo daily for 7-12 years	Drug: vitamin E placebo; daily for 7-12 years; Other Names: placebo ; Drug: selenium placebo; daily for 7-12 years; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Visually Significant Age-related Macular Degeneration (AMD) [Every 6 months, up to 7 years]

   Visually significant age-related AMD was defined as incident AMD responsible for reduction in best corrected visual acuity to 20/30 or worse(AMD 20/30)

2. Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30 [Every 6 months, up to 7 years]

   Incident cataract was defined as lens opacity diagnosed after randomization but prior to end of study, age-related in origin, and best-corrected visual acuity of 20/30 or worse attributable to the opacity.

Secondary Outcome Measures

1. Number of Participants With Advanced AMD [Every 6 months, up to 7 years]

   Advanced AMD was defined as the occurrence of disciform scars, or geographic atrophy or retinal pigment epithelium (RPE) detachment in either or both eyes at AMD diagnosis.

2. Number of Participants Who Underwent Cataract Extraction [Every 6 months, up to 7 years]

   Cataract extraction was defined as the surgical removal of an incident cataract.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

DISEASE CHARACTERISTICS:

• Enrolled on the Selenium and Vitamin E Prostate Cancer Prevention Trial (SELECT) SWOG-S0000

• Diagnosis of 1 of the following:

• Age-related macular degeneration (AMD) at baseline or at follow-up

• Cataract or a cataract extraction at follow-up (Closed for accrual as of 10/01/29)

• Participants with a prior diagnosis of cataract at baseline followed by another cataract event (cataract diagnosis or a cataract extraction) at follow-up are not eligible

• Participants with a prior diagnosis of cataract at baseline followed by a diagnosis of AMD at follow-up are eligible

PATIENT CHARACTERISTICS:

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

• Not applicable

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harvard Medical School	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• National Eye Institute (NEI)

Investigators

• Study Chair: William Christen, ScD, Dana-Farber/Brigham and Women's Cancer Center

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Oct 19, 2009

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00784225
• Other Study ID Numbers: CDR0000617778; S0000B; U10CA037429; R01EY014418
• First Posted: Nov 2, 2008
• Last Update Posted: Aug 14, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Southwest Oncology Group: cataract; advanced macular degeneration
• Additional relevant MeSH terms: Macular Degeneration; Cataract; Vitamins; Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; Selenium

Study Results

Participant Flow

Arm/Group Title	Selenium + Vitamin E Placebo	Selenium + Vitamin E	Vitamin E Placebo + Selenium Placebo	Vitamin E + Selenium Placebo
Arm/Group Description	Patients received selenium and vitamin E placebo daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received selenium and vitamin E daily for 7 - 12 years Selenium: 200 mcg 1 pill by mouth daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years	Patients received vitamin E placebo and selenium placebo daily for 7 - 12 years Vitamin E placebo:1 pill daily by mouth for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E and selenium placebo daily for 7 - 12 years Vitamin E: 400 IU by mouth daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years
Period Title: Overall Study
STARTED	3375	3357	3369	3374
COMPLETED	3375	3357	3369	3374
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Selenium + Vitamin E Placebo	Selenium + Vitamin E	Vitamin E Placebo + Selenium Placebo	Vitamin E + Selenium Placebo	Total
Arm/Group Description	Selenium and vitamin E placebo daily for 7-12 years. Selenium: 200 mcg daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Selenium and vitamin E daily for 7-12 years. Selenium: 200 mcg daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years	Vitamin E placebo and selenium placebo daily for 7-12 years. Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Vitamin E and selenium placebo daily for 7-12 years. Vitamin E: 400 IU daily by mouth for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Total of all reporting groups
Overall Participants	3375	3357	3369	3374	13475
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	62	62	62	62	62
Age, Customized (Count of Participants)
50-54 years	134 4%	160 4.8%	159 4.7%	155 4.6%	608 4.5%
55-64 years	1951 57.8%	1964 58.5%	1959 58.1%	2027 60.1%	7901 58.6%
65-74 years	1065 31.6%	1067 31.8%	1061 31.5%	993 29.4%	4186 31.1%
>=75 years	225 6.7%	166 4.9%	190 5.6%	199 5.9%	780 5.8%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	3375 100%	3357 100%	3369 100%	3374 100%	13475 100%
Race/Ethnicity, Customized (Count of Participants)
White	2753 81.6%	2756 82.1%	2750 81.6%	2763 81.9%	11022 81.8%
Non-white	622 18.4%	601 17.9%	619 18.4%	611 18.1%	2453 18.2%
Education (highest level) (Count of Participants)
<= High school graduate or GED	653 19.3%	641 19.1%	706 21%	656 19.4%	2656 19.7%
Some college/vocational school	943 27.9%	943 28.1%	948 28.1%	964 28.6%	3798 28.2%
>College graduate	1759 52.1%	1752 52.2%	1705 50.6%	1738 51.5%	6954 51.6%
Unknown/missing	20 0.6%	21 0.6%	10 0.3%	16 0.5%	67 0.5%
Cigarette smoking (Count of Participants)
Never	1451 43%	1419 42.3%	1366 40.5%	1457 43.2%	5693 42.2%
Current	248 7.3%	278 8.3%	319 9.5%	268 7.9%	1113 8.3%
Former	1670 49.5%	1654 49.3%	1681 49.9%	1642 48.7%	6647 49.3%
Unknown	6 0.2%	6 0.2%	3 0.1%	7 0.2%	22 0.2%
Alcohol use (Count of Participants)
Rarely/never	50 1.5%	51 1.5%	66 2%	59 1.7%	226 1.7%
>=1 drink/month	3325 98.5%	3304 98.4%	3303 98%	3314 98.2%	13246 98.3%
Unknown	0 0%	2 0.1%	0 0%	1 0%	3 0%
Body mass index (kg/m^2) (Count of Participants)
<25	674 20%	666 19.8%	675 20%	626 18.6%	2641 19.6%
25-<30	1574 46.6%	1607 47.9%	1591 47.2%	1606 47.6%	6378 47.3%
>=30	1127 33.4%	1084 32.3%	1103 32.7%	1142 33.8%	4456 33.1%
History of hypertension (Count of Participants)
Yes	1339 39.7%	1320 39.3%	1374 40.8%	1301 38.6%	5334 39.6%
No	2036 60.3%	2037 60.7%	1995 59.2%	2073 61.4%	8141 60.4%
Aspirin use (Count of Participants)
Yes	1484 44%	1454 43.3%	1505 44.7%	1481 43.9%	5924 44%
No	1891 56%	1903 56.7%	1864 55.3%	1893 56.1%	7551 56%
Statin use (Count of Participants)
Yes	884 26.2%	886 26.4%	900 26.7%	914 27.1%	3584 26.6%
No	2464 73%	2447 72.9%	2451 72.8%	2434 72.1%	9796 72.7%
Unknown	27 0.8%	24 0.7%	18 0.5%	26 0.8%	95 0.7%
History of diabetes (Count of Participants)
Yes	353 10.5%	348 10.4%	380 11.3%	339 10%	1420 10.5%
No	3022 89.5%	3009 89.6%	2989 88.7%	3035 90%	12055 89.5%
Records sought (Count of Participants)
Yes	635 18.8%	624 18.6%	624 18.5%	629 18.6%	2512 18.6%
No	2740 81.2%	2733 81.4%	2745 81.5%	2745 81.4%	10963 81.4%
Included in cataract analysis (Count of Participants)
Yes	2805 83.1%	2789 83.1%	2829 84%	2844 84.3%	11267 83.6%
No	570 16.9%	568 16.9%	540 16%	530 15.7%	2208 16.4%
Included in AMD analysis (Count of Participants)
Yes	3348 99.2%	3342 99.6%	3355 99.6%	3344 99.1%	13389 99.4%
No	27 0.8%	15 0.4%	14 0.4%	30 0.9%	86 0.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Visually Significant Age-related Macular Degeneration (AMD)
Description	Visually significant age-related AMD was defined as incident AMD responsible for reduction in best corrected visual acuity to 20/30 or worse(AMD 20/30)
Time Frame	Every 6 months, up to 7 years

Outcome Measure Data

Analysis Population Description

Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.

Arm/Group Title	AMD: Selenium Active	AMD: Selenium Placebo	AMD: Vitamin E Active	AMD: Vitamin E Placebo
Arm/Group Description	Patients received selenium and either Vitamin E or vitamin E placebo daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received selenium placebo and either Vitamin E or vitamin E placebo daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E and either selenium or selenium placebo daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E placebo and either selenium or selenium placebo daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years
Measure Participants	6690	6699	6686	6703
AMD cases	9 0.3%	12 0.4%	9 0.3%	12 0.4%
non-AMD cases	6681 198%	6687 199.2%	6677 198.2%	6691 198.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMD: Selenium Active, AMD: Selenium Placebo
	Comments	Statistical analysis for number of participants with visually significant AMD in SEE sites during pill-taking for selenium
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.32 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AMD: Vitamin E Active, AMD: Vitamin E Placebo
	Comments	Statistical analysis for number of participants with visually significant AMD in SEE sites during pill-taking for vitamin E
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Cataract and Best Corrected Visual-acuity of 20/30
Description	Incident cataract was defined as lens opacity diagnosed after randomization but prior to end of study, age-related in origin, and best-corrected visual acuity of 20/30 or worse attributable to the opacity.
Time Frame	Every 6 months, up to 7 years

Outcome Measure Data

Analysis Population Description

Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.

Arm/Group Title	Cataract: Selenium Active	Cataract: Selenium Placebo	Cataract: Vitamin E Active	Cataract: Vitamin E Placebo
Arm/Group Description	Patients received selenium and either vitamin E or vitamin E placebo daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received selenium placebo and either vitamin E or vitamin E placebo daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E and either selenium or selenium placebo daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E placebo and either selenium or selenium placebo daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years
Measure Participants	5594	5673	5633	5634
Cataract cases	185 5.5%	204 6.1%	197 5.8%	192 5.7%
non-cataract cases	5409 160.3%	5469 162.9%	5436 161.4%	5442 161.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMD: Selenium Active, AMD: Selenium Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AMD: Vitamin E Active, AMD: Vitamin E Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.81
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Advanced AMD
Description	Advanced AMD was defined as the occurrence of disciform scars, or geographic atrophy or retinal pigment epithelium (RPE) detachment in either or both eyes at AMD diagnosis.
Time Frame	Every 6 months, up to 7 years

Outcome Measure Data

Analysis Population Description

Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.

Arm/Group Title	AMD: Selenium Active	AMD: Selenium Placebo	AMD: Vitamin E Active	AMD: Vitamin E Placebo
Arm/Group Description	Patients received selenium and either Vitamin E or vitamin E placebo daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received selenium placebo and either Vitamin E or vitamin E placebo daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E and either selenium or selenium placebo daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E placebo and either selenium or selenium placebo daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years
Measure Participants	6690	6699	6686	6703
Advanced AMD cases	10 0.3%	4 0.1%	7 0.2%	7 0.2%
non-advanced AMD cases	6680 197.9%	6695 199.4%	6679 198.2%	6696 198.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMD: Selenium Active, AMD: Selenium Placebo
	Comments	Statistical analysis for number of participants with advanced AMD in SEE sites during pill-taking for selenium
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	2.5
	Confidence Interval	(2-Sided) 95%; 0.79 to 7.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AMD: Vitamin E Active, AMD: Vitamin E Placebo
	Comments	Statistical analysis for number of participants with advanced AMD in SEE sites during pill-taking for vitamin E
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.35 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants Who Underwent Cataract Extraction
Description	Cataract extraction was defined as the surgical removal of an incident cataract.
Time Frame	Every 6 months, up to 7 years

Outcome Measure Data

Analysis Population Description

Marginal analyses were performed with arms pooled based on active vs. placebo selenium or vitamin E.

Arm/Group Title	Cataract: Selenium Active	Cataract: Selenium Placebo	Cataract: Vitamin E Active	Cataract: Vitamin E Placebo
Arm/Group Description	Patients received selenium and either vitamin E or vitamin E placebo daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received selenium placebo and either vitamin E or vitamin E placebo daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E and either selenium or selenium placebo daily for 7 - 12 years Vitamin E: 400 IU daily by mouth for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years	Patients received vitamin E placebo and either selenium or selenium placebo daily for 7 - 12 years Vitamin E placebo: 1 pill by mouth daily for 7 - 12 years Selenium: 200 mcg daily for 7 - 12 years Selenium placebo: 1 pill by mouth daily for 7 - 12 years
Measure Participants	5594	5673	5633	5634
Cataract extraction cases	99 2.9%	120 3.6%	114 3.4%	105 3.1%
non-cataract extraction cases	5495 162.8%	5553 165.4%	5519 163.8%	5529 163.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AMD: Selenium Active, AMD: Selenium Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AMD: Vitamin E Active, AMD: Vitamin E Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Every 6 months while the participant is receiving study supplements, up to 7 years
Adverse Event Reporting Description	There are no Adverse Events (AE) associated with this trial. All AEs were reported for the parent trial (SELECT - S0000). Included below are the AEs for the participants on this trial that were included in the primary analysis. These AEs were also reported for the parent trial.
Arm/Group Title	Selenium + Vitamin E Placebo		Selenium + Vitamin E		Placebo		Vitamin E + Selenium Placebo
Arm/Group Description	Selenium + Vitamin E placebo		Selenium + Vitamin E		Placebo		Vitamin E + Selenium placebo
All Cause Mortality
	Selenium + Vitamin E Placebo		Selenium + Vitamin E		Placebo		Vitamin E + Selenium Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/3374 (4.5%)		159/3356 (4.7%)		150/3366 (4.5%)		147/3374 (4.4%)
Serious Adverse Events
	Selenium + Vitamin E Placebo		Selenium + Vitamin E		Placebo		Vitamin E + Selenium Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/3374 (1.3%)		41/3356 (1.2%)		50/3366 (1.5%)		45/3374 (1.3%)
Cardiac disorders
Arrhythmia, NOS	1/3374 (0%)		1/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Cardiac ischemia/infarction	11/3374 (0.3%)		9/3356 (0.3%)		9/3366 (0.3%)		8/3374 (0.2%)
Cardiovascular-other	7/3374 (0.2%)		9/3356 (0.3%)		15/3366 (0.4%)		12/3374 (0.4%)
Conduction abnormality/block	0/3374 (0%)		1/3356 (0%)		0/3366 (0%)		0/3374 (0%)
LVEF decrease/CHF	2/3374 (0.1%)		0/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Supraventricular arrhythmia	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Ventricular arrhythmia	1/3374 (0%)		1/3356 (0%)		3/3366 (0.1%)		2/3374 (0.1%)
Eye disorders
Eye-other	0/3374 (0%)		0/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Vision,NOS	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Gastrointestinal disorders
GI-other	0/3374 (0%)		1/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Melena/ GI bleeding	1/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
General disorders
Constitutional symptoms-other	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Hemorrhage w/o 3-4 thrombocyt	0/3374 (0%)		0/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Reportable adverse event, NOS	8/3374 (0.2%)		7/3356 (0.2%)		11/3366 (0.3%)		8/3374 (0.2%)
Hepatobiliary disorders
Liver-clinical	0/3374 (0%)		0/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Infections and infestations
Respiratory infect w/o neutrop	2/3374 (0.1%)		0/3356 (0%)		1/3366 (0%)		1/3374 (0%)
Respiratory infection, unk ANC	0/3374 (0%)		0/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Injury, poisoning and procedural complications
Surgery-hemorrhage	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Investigations
Weight gain	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second primary	3/3374 (0.1%)		4/3356 (0.1%)		1/3366 (0%)		0/3374 (0%)
Nervous system disorders
CNS hemorrhage	2/3374 (0.1%)		2/3356 (0.1%)		0/3366 (0%)		3/3374 (0.1%)
Cerebrovascular ischemia	2/3374 (0.1%)		4/3356 (0.1%)		1/3366 (0%)		4/3374 (0.1%)
Seizures	1/3374 (0%)		0/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Sensory neuropathy	0/3374 (0%)		1/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		1/3374 (0%)
Emphysema/COPD	1/3374 (0%)		0/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Epistaxis	1/3374 (0%)		0/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Pulmonary fibrosis	1/3374 (0%)		0/3356 (0%)		0/3366 (0%)		0/3374 (0%)
Vascular disorders
Carotid stenosis	0/3374 (0%)		1/3356 (0%)		0/3366 (0%)		1/3374 (0%)
Peripheral arterial ischemia	0/3374 (0%)		1/3356 (0%)		1/3366 (0%)		0/3374 (0%)
Thrombosis/embolism	0/3374 (0%)		0/3356 (0%)		1/3366 (0%)		1/3374 (0%)
Other (Not Including Serious) Adverse Events
	Selenium + Vitamin E Placebo		Selenium + Vitamin E		Placebo		Vitamin E + Selenium Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	243/3374 (7.2%)		243/3356 (7.2%)		261/3366 (7.8%)		267/3374 (7.9%)
Cardiac disorders
Cardiac ischemia/infarction	243/3374 (7.2%)		243/3356 (7.2%)		261/3366 (7.8%)		267/3374 (7.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.