The Estrogen Replacement and Atherosclerosis Trial ; Primary Outcome Measure is Mean Minimal Coronary Artery Diameter After Avg of 3.2 Yrs.

NCT03097120 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: U01HL45488
• Study Type: interventional
• Target: 309
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. Methods: The investigators randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (±SD) of 3.2±0.6 years. Base-line and follow-up coronary angiograms were were analyzed by quantitative methods. Follow-up coronary angiograms were obtained after an average of 3.2 years of follow up.

Conditions

Heart Disease

Outcome Measures

Primary Outcomes (1)

• mean minimal coronary-artery diameter

  mean minimal coronary-artery diameter within each subject at follow-up, analyzed on an intention-to-treat basis

  at average of 3.2 years follow-up

Secondary Outcomes (3)

• stenosis as a percentage of the reference diameter

  at average of 3.2 years follow-up

• development of new lesions in a patient

  at average of 3.2 years follow-up

• Models focusing on change in diameter were also examined

  at average of 3.2 years follow-up

Study Arms (3)

unopposed estrogen

ACTIVE COMPARATOR

0.625 mg of conjugated equine estrogen

Drug: 0.625 mg of conjugated equine estrogen

estrogen-plus-medroxyprogesterone

ACTIVE COMPARATOR

0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate

Drug: 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo tablets

Interventions

0.625 mg of conjugated equine estrogen DRUG

one tablet containing 0.625 mg of conjugated equine estrogen and a placebo tablet daily

unopposed estrogen

0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate DRUG

one tablet of 0.625 mg of conjugated equine estrogen plus one tablet 2.5 mg of medroxyprogesterone acetate daily

estrogen-plus-medroxyprogesterone

placebo tablets DRUG

two placebo tablets daily

placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• postmenopausal
• not currently receiving estrogen-replacement treatment
• one or more epicardial coronary stenoses of at least 30 percent of the luminal diameter, as measured by quantitative coronary angiography

You may not qualify if:

• known or suspected breast or endometrial carcinoma
• previous or planned coronary-artery bypass surgery,
• a history of deep-vein thrombosis or pulmonary embolism,
• symptomatic gallstones,
• serum aspartate aminotransferase level more than 1.5 times the normal value,
• fasting triglyceride level of more than 400 mg per deciliter
• serum creatinine level of more than 2.0 mg per deciliter
• more than 70 percent stenosis of the left main coronary artery,
• uncontrolled hypertension, or
• uncontrolled diabetes.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (2)

• Herrington DM, Reboussin DM, Klein KP, Sharp PC, Shumaker SA, Snyder TE, Geisinger KR. The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort. Control Clin Trials. 2000 Jun;21(3):257-85. doi: 10.1016/s0197-2456(00)00054-4.

  PMID: 10822123 BACKGROUND

• Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, Furberg CD, Kowalchuk GJ, Stuckey TD, Rogers WJ, Givens DH, Waters D. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000 Aug 24;343(8):522-9. doi: 10.1056/NEJM200008243430801.

  PMID: 10954759 RESULT

MeSH Terms

Conditions

Heart Diseases

Interventions

Estrogens, Conjugated (USP); Medroxyprogesterone Acetate

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• David M. Herrington, MD, MHS

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: March 31, 2017
• Study Start: January 1, 1995
• Primary Completion: January 1, 2001
• Study Completion: January 1, 2001
• Last Updated: May 22, 2023

Record last verified: 2018-07

Locations

US (1)