Trial Outcomes & Findings for ELITE: Early Versus Late Intervention Trial With Estradiol (NCT NCT00114517)

Last Updated: 2023-01-18

Results Overview

Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (mm per year) in computer image processed B-mode ultrasonograms that were obtained at two baseline examinations (averaged to obtain the baseline CIMT value) and every 6 months during trial follow-up.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

643 participants

Primary outcome timeframe

Baseline x 2 and then every 6 months up to 6.7 years

Results posted on

2023-01-18

Participant Flow

Participants were recruited from the general population through media campaigns.

2166 individuals were screened by telephone, 1,271 were ineligible. 895 individuals were screened in research clinic, 252 were excluded (133 did not meet inclusion criteria; 119 declined to participate). 643 individuals were randomized.

Participant milestones

Participant milestones
Measure	Early Postmenopause 17B-estradiol Early postmenopause, \<6 years-since-menopause, Oral 17B-estradiol 1 mg daily	Early Postmenopause Placebo Early postmenopause, \<6 years-since-menopause, Matching oral 17B-estradiol placebo daily	Late Postmenopause 17B-estradiol Late postmenopause, \>10 years-since-menopause, Oral 17B-estradiol 1 mg daily	Late Postmenopause Placebo Late postmenopause, \>10 years-since-menopause, Matching oral 17B-estradiol placebo daily
Overall Study STARTED	137	134	186	186
Overall Study COMPLETED	125	123	172	176
Overall Study NOT COMPLETED	12	11	14	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Early Postmenopause 17B-estradiol Early postmenopause, \<6 years-since-menopause, Oral 17B-estradiol 1 mg daily	Early Postmenopause Placebo Early postmenopause, \<6 years-since-menopause, Matching oral 17B-estradiol placebo daily	Late Postmenopause 17B-estradiol Late postmenopause, \>10 years-since-menopause, Oral 17B-estradiol 1 mg daily	Late Postmenopause Placebo Late postmenopause, \>10 years-since-menopause, Matching oral 17B-estradiol placebo daily
Overall Study Adverse Event	6	1	6	3
Overall Study Lost to Follow-up	2	2	2	1
Overall Study Too busy	3	1	1	2
Overall Study Moved from area	0	3	2	1
Overall Study Did not want estradiol	1	1	0	0
Overall Study Armed-services duty	0	1	0	1
Overall Study Competing family issue	0	1	0	1
Overall Study Physician Decision	0	1	0	0
Overall Study Lost interest	0	0	1	0
Overall Study Weight increase	0	0	1	0
Overall Study Concern about blood clots	0	0	1	0
Overall Study Breast cancer diagnosis on baseline mammogram	0	0	0	1

Baseline Characteristics

ELITE: Early Versus Late Intervention Trial With Estradiol

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Early Postmenopause 17B-estradiol n=125 Participants Early postmenopause, \<6 years-since-menopause, Oral 17B-estradiol 1 mg daily	Early Postmenopause Placebo n=123 Participants Early postmenopause, \<6 years-since-menopause, Matching oral 17B-estradiol placebo daily	Late Postmenopause 17B-estradiol n=172 Participants Late postmenopause, \>10 years-since-menopause, Oral 17B-estradiol 1 mg daily	Late Postmenopause Placebo n=176 Participants Late postmenopause, \>10 years-since-menopause, Matching oral 17B-estradiol placebo daily	Total n=596 Participants Total of all reporting groups
Age, Continuous	55.4 years n=99 Participants	55.4 years n=107 Participants	64.3 years n=206 Participants	63.0 years n=7 Participants	60.0 years n=31 Participants
Sex: Female, Male Female	125 Participants n=99 Participants	123 Participants n=107 Participants	172 Participants n=206 Participants	176 Participants n=7 Participants	596 Participants n=31 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race/Ethnicity, Customized White, non-hispanic	88 Participants n=99 Participants	73 Participants n=107 Participants	127 Participants n=206 Participants	127 Participants n=7 Participants	415 Participants n=31 Participants
Race/Ethnicity, Customized Black, non-hispanic	7 Participants n=99 Participants	14 Participants n=107 Participants	17 Participants n=206 Participants	14 Participants n=7 Participants	52 Participants n=31 Participants
Race/Ethnicity, Customized Hispanic	16 Participants n=99 Participants	20 Participants n=107 Participants	20 Participants n=206 Participants	23 Participants n=7 Participants	79 Participants n=31 Participants
Race/Ethnicity, Customized Asian	14 Participants n=99 Participants	16 Participants n=107 Participants	8 Participants n=206 Participants	12 Participants n=7 Participants	50 Participants n=31 Participants

PRIMARY outcome

Timeframe: Baseline x 2 and then every 6 months up to 6.7 years

Population: Early postmenopause group (\<6 years-since-menopause) at baseline and late postmenopause group (\>10 years-since-menopause) at baseline.

Outcome measures

Outcome measures
Measure	17B-estradiol n=297 Participants Oral 17B-estradiol 1 mg daily	Placebo n=299 Participants Matching oral 17B-estradiol placebo daily
Progression of Subclinical Atherosclerosis Late postmenopause group	0.0100 mm per year Interval 0.0085 to 0.0115	0.0088 mm per year Interval 0.0073 to 0.0103
Progression of Subclinical Atherosclerosis Early postmenopause group	0.0044 mm per year Interval 0.0026 to 0.0061	0.0078 mm per year Interval 0.006 to 0.0096

SECONDARY outcome

Timeframe: Baseline and at 2.5 years and 5 years

Population: Sample size represents the number of participants with analyzable data collected at baseline, 2.5 years, and 5.0 years. Early postmenopause group (\<6 years-since-menopause) at baseline and late postmenopause group (\>10 years-since-menopause) at baseline.

All neuropsychological test scores at baseline and follow-up assessments were standardized (\[raw score - mean score\]/standard deviation) using the baseline means and standard deviations from the entire ELITE sample. Each of three cognitive composite scores was calculated at baseline and follow-up assessments as the weighted average of the individual donor standardized test scores, weighted by the inverse correlation among tests.The change from baseline (endpoint minus baseline cognitive outcome) was computed for each of the cognitive scores (verbal memory, global cognition, and executive functions). Since the outcome is not a single test but a weighted average of multiple tests, the range is not standard and not reported. Higher scores mean better outcomes.

Outcome measures

Outcome measures
Measure	17B-estradiol n=284 Participants Oral 17B-estradiol 1 mg daily	Placebo n=283 Participants Matching oral 17B-estradiol placebo daily
Change in Neurocognitive Function (Global Cognition) Early postmenopause group	0.42 units on a scale Interval 0.11 to 0.73	0.40 units on a scale Interval -0.07 to 0.72
Change in Neurocognitive Function (Global Cognition) Late postmenopause group	0.29 units on a scale Interval 0.14 to 0.44	0.36 units on a scale Interval 0.2 to 0.53

SECONDARY outcome

Timeframe: End of randomized treatment, up to 6.7 years

Population: CAC data was obtained in 380 participants. Participants who were not taking the study products at the last follow-up visit, who had adherence to the study regimen that was lower than 80%, or who had a CAC scan more than 6 months after the final study visit were not included in the analysis. Early postmenopause group (\<6 years-since-menopause) at baseline and late postmenopause group (\>10 years-since-menopause) at baseline.

Number of participants with coronary artery calcium measured by cardiac computed tomography

Outcome measures

Outcome measures
Measure	17B-estradiol n=188 Participants Oral 17B-estradiol 1 mg daily	Placebo n=192 Participants Matching oral 17B-estradiol placebo daily
Coronary Artery Calcium Early postmenopause group	34 Participants	24 Participants
Coronary Artery Calcium Late postmenopause group	57 Participants	65 Participants

Adverse Events

17B-estradiol

Serious events: 43 serious events

Other events: 216 other events

Deaths: 1 deaths

Placebo

Serious events: 45 serious events

Other events: 226 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Howard N. Hodis, M.D., Director, Atherosclerosis Research Unit

University of Southern California

Phone: 323-442-1478

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	17B-estradiol n=323 participants at risk Oral 17B-estradiol 1 mg daily	Placebo n=320 participants at risk Matching oral 17B-estradiol placebo daily
Blood and lymphatic system disorders aplastic anemia	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Cardiac disorders unstable angina	0.62% 2/323 • Number of events 2 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Cardiac disorders atrial fibrillation	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Cardiac disorders pleuropericarditis	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Cardiac disorders myocardial infarction	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.94% 3/320 • Number of events 3 Adverse events collected per intervention
Ear and labyrinth disorders veritgo	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Gastrointestinal disorders ischemic colitis	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Gastrointestinal disorders gastroesophageal reflux disease	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Gastrointestinal disorders illeitis	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Gastrointestinal disorders gastrointestinal hemorrhage	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Gastrointestinal disorders pancreatitis	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
General disorders death	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
General disorders non-cardiac chest pain	0.62% 2/323 • Number of events 2 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Immune system disorders drug hypersensitivity	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Infections and infestations cellulitis	0.00% 0/323 Adverse events collected per intervention	0.62% 2/320 • Number of events 2 Adverse events collected per intervention
Infections and infestations lobar pneumonia	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Infections and infestations pelvic abscess	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Infections and infestations pneumonia	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Injury, poisoning and procedural complications cervical vertebral fracture	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Injury, poisoning and procedural complications femoral neck fracture	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.94% 3/320 • Number of events 3 Adverse events collected per intervention
Injury, poisoning and procedural complications foot fracture	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Injury, poisoning and procedural complications fracture	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Musculoskeletal and connective tissue disorders systemic lupus erythematosus	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) breast cancer	1.5% 5/323 • Number of events 5 Adverse events collected per intervention	1.2% 4/320 • Number of events 4 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) breast cancer in situ	1.5% 5/323 • Number of events 5 Adverse events collected per intervention	1.2% 4/320 • Number of events 4 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) colon adenoma	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) colorectal cancer	0.93% 3/323 • Number of events 3 Adverse events collected per intervention	0.62% 2/320 • Number of events 2 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) gastric cancer	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) glioblastoma	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignant peritoneal neoplasm	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) mycosis fungoides	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ovarian epithelial cancer	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) pancreatic carcinoma	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) polycythemia vera	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Neoplasms benign, malignant and unspecified (incl cysts and polyps) uterine cancer	0.62% 2/323 • Number of events 2 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Nervous system disorders amnesia	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Nervous system disorders dizziness	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Nervous system disorders syncope	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Nervous system disorders transient ischemic attack	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.62% 2/320 • Number of events 2 Adverse events collected per intervention
Psychiatric disorders Suicide ideation	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Psychiatric disorders psychotic disorder	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Respiratory, thoracic and mediastinal disorders pulmonary embolism	0.62% 2/323 • Number of events 2 Adverse events collected per intervention	0.00% 0/320 Adverse events collected per intervention
Surgical and medical procedures spinal laminectomy	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention
Vascular disorders deep vein thrombosis	0.31% 1/323 • Number of events 1 Adverse events collected per intervention	0.62% 2/320 • Number of events 2 Adverse events collected per intervention
Gastrointestinal disorders ulcerative colitis	0.00% 0/323 Adverse events collected per intervention	0.31% 1/320 • Number of events 1 Adverse events collected per intervention

Measure	17B-estradiol n=323 participants at risk Oral 17B-estradiol 1 mg daily	Placebo n=320 participants at risk Matching oral 17B-estradiol placebo daily
General disorders chest discomfort	7.1% 23/323 • Number of events 23 Adverse events collected per intervention	6.9% 22/320 • Number of events 22 Adverse events collected per intervention
General disorders non-cardiac chest pain	5.6% 18/323 • Number of events 18 Adverse events collected per intervention	3.8% 12/320 • Number of events 12 Adverse events collected per intervention
Immune system disorders drug hypersensitivity	8.0% 26/323 • Number of events 26 Adverse events collected per intervention	7.8% 25/320 • Number of events 25 Adverse events collected per intervention
Infections and infestations bronchitis	5.9% 19/323 • Number of events 19 Adverse events collected per intervention	6.9% 22/320 • Number of events 22 Adverse events collected per intervention
Infections and infestations influenza	13.6% 44/323 • Number of events 44 Adverse events collected per intervention	16.2% 52/320 • Number of events 52 Adverse events collected per intervention
Infections and infestations sinusitis	7.4% 24/323 • Number of events 24 Adverse events collected per intervention	7.5% 24/320 • Number of events 24 Adverse events collected per intervention
Infections and infestations urinary tract infection	19.5% 63/323 • Number of events 63 Adverse events collected per intervention	20.0% 64/320 • Number of events 64 Adverse events collected per intervention
Injury, poisoning and procedural complications contusion	5.3% 17/323 • Number of events 17 Adverse events collected per intervention	3.8% 12/320 • Number of events 12 Adverse events collected per intervention
Injury, poisoning and procedural complications fall	11.5% 37/323 • Number of events 37 Adverse events collected per intervention	11.2% 36/320 • Number of events 36 Adverse events collected per intervention
Injury, poisoning and procedural complications road traffic accident	5.9% 19/323 • Number of events 19 Adverse events collected per intervention	4.1% 13/320 • Number of events 13 Adverse events collected per intervention
Musculoskeletal and connective tissue disorders arthralgia	14.6% 47/323 • Number of events 47 Adverse events collected per intervention	16.6% 53/320 • Number of events 53 Adverse events collected per intervention
Musculoskeletal and connective tissue disorders back pain	10.8% 35/323 • Number of events 35 Adverse events collected per intervention	10.0% 32/320 • Number of events 32 Adverse events collected per intervention
Musculoskeletal and connective tissue disorders pain in extremity	3.1% 10/323 • Number of events 10 Adverse events collected per intervention	5.6% 18/320 • Number of events 18 Adverse events collected per intervention
Psychiatric disorders depression	5.3% 17/323 • Number of events 17 Adverse events collected per intervention	6.2% 20/320 • Number of events 20 Adverse events collected per intervention
Reproductive system and breast disorders cervical dysplasia	14.9% 48/323 • Number of events 48 Adverse events collected per intervention	13.1% 42/320 • Number of events 42 Adverse events collected per intervention
Reproductive system and breast disorders vaginal discharge	5.3% 17/323 • Number of events 17 Adverse events collected per intervention	2.5% 8/320 • Number of events 8 Adverse events collected per intervention
Reproductive system and breast disorders vulvovaginal pruritis	5.9% 19/323 • Number of events 19 Adverse events collected per intervention	3.4% 11/320 • Number of events 11 Adverse events collected per intervention
Respiratory, thoracic and mediastinal disorders cough	7.7% 25/323 • Number of events 25 Adverse events collected per intervention	5.9% 19/320 • Number of events 19 Adverse events collected per intervention
Skin and subcutaneous tissue disorders rash	5.0% 16/323 • Number of events 16 Adverse events collected per intervention	6.9% 22/320 • Number of events 22 Adverse events collected per intervention