NCT02524561

Brief Summary

Combined estrogen and progestin therapy has been shown to increase mammographic density and incidence of breast cancer in randomized trials. The investigators propose to examine the effects of now commonly used low-dose combined hormone therapy (HT) regimens on breast density, rates of abnormal mammogram, and circulating estrogens in the ongoing, already-funded Kronos Early Estrogen Prevention Study (KEEPS). KEEPS is a randomized clinical trial with a primary goal of examining the effects of low-dose transdermal versus oral estrogen combined with cyclic micronized progesterone on progression of subclinical atherosclerosis in recently menopausal women. Prior studies of low-dose HT have been of short duration and small size. By determining the effects of low-dose hormone therapy on the breast, the proposed ancillary study will add important information about the estimated balance of risks and benefits associated with low-dose HT and will help guide future research trials.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
517

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2005

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2005

Completed
8.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

August 13, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 17, 2015

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

March 8, 2017

Completed
Last Updated

March 8, 2017

Status Verified

January 1, 2017

Enrollment Period

8.3 years

First QC Date

August 13, 2015

Results QC Date

September 20, 2016

Last Update Submit

January 18, 2017

Conditions

Keywords

mammographic densityabnormal mammogrambiopsy

Outcome Measures

Primary Outcomes (3)

  • BIRADS Breast Density

    Breast density prior to randomization. Frequency of the BIRADS category according to randomization status. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.

    Baseline (Prior to Randomization)

  • BIRADS Breast Density

    Frequency of the BIRADS category 1 year after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.

    Year 1

  • BIRADS Breast Density

    Frequency of the BIRADS category 3-4 years after randomization. BIRADS is a 1-4 category of breast density as assessed by a radiologist. 1= most fatty and least dense, while 4=most dense.

    Latest (Year 3 of 4)

Secondary Outcomes (1)

  • Abnormal Mammogram/Biopsy

    baseline to 3 years

Study Arms (3)

CEE pill, active progesterone

ACTIVE COMPARATOR

Conjugated equine estrogens 0.45 mg/day, placebo patch, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime

Drug: CEE pillDrug: Active ProgesteroneOther: Placebo patch

estradiol patch, active progesterone

ACTIVE COMPARATOR

Transdermal estradiol, 50 mcg/day, placebo tablet, Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime

Drug: Estradiol patchDrug: Active ProgesteroneOther: Placebo tablet

placebo

PLACEBO COMPARATOR

Placebo tablet, placebo patch, placebo progesterone

Other: Placebo tabletOther: Placebo patchOther: Placebo progesterone

Interventions

Conjugated equine estrogens 0.45 mg/day

Also known as: premarin
CEE pill, active progesterone

Climara 50 mcg/day

Also known as: Climara 50 mcg/day
estradiol patch, active progesterone

Prometrium (micronized progesterone USP encapsulated with peanut oil) 200 mg daily for the first 12 days of each month at bedtime

CEE pill, active progesteroneestradiol patch, active progesterone

Placebo tablet

estradiol patch, active progesteroneplacebo

placebo patch

CEE pill, active progesteroneplacebo

placebo progesterone

placebo

Eligibility Criteria

Age42 Years - 58 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Women were 42-58 years of age, have had cessation of menses at or after age 40 and no menses for a minimum of 6 and a maximum of 36 months at screening.
  • Subjects may or may not have had current vasomotor estrogen deficiency symptoms, had not taken estrogen- or progestogen-containing medication (oral contraceptive or hormone replacement) within 3 months of randomization, and had plasma FSH levels measured at ≥35 ng/ml and plasma E2 levels of \<40 pg/ml.

You may not qualify if:

  • Subjects were excluded for increased endometrial thickness on ultrasound \>5 mm, unless endometrial biopsy was negative; for LDL ≥ 190 mg/dl or triglycerides ≥ 400 at screening, or use of lipid lowering drugs.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

2-chloroethyl ethyl sulfideEstrogens, Conjugated (USP)Ortho EvraEstradiol

Intervention Hierarchy (Ancestors)

Estradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsEstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Dr. Rulla Tamimi
Organization
Brigham and Women's Hospital

Study Officials

  • Kathy Rexrode, MD

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

August 13, 2015

First Posted

August 17, 2015

Study Start

September 1, 2005

Primary Completion

December 1, 2013

Study Completion

December 1, 2013

Last Updated

March 8, 2017

Results First Posted

March 8, 2017

Record last verified: 2017-01

Locations