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

The Estrogen Replacement and Atherosclerosis Trial

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.

Study Overview

• Status: Completed
• Conditions: Heart Disease
• Intervention / Treatment: Drug: 0.625 mg of conjugated equine estrogen; Drug: 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate; Drug: placebo tablets

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo tablets; two placebo tablets daily
Active Comparator: unopposed estrogen; 0.625 mg of conjugated equine estrogen	Drug: 0.625 mg of conjugated equine estrogen; one tablet containing 0.625 mg of conjugated equine estrogen and a placebo tablet daily
Active Comparator: estrogen-plus-medroxyprogesterone; 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; one tablet of 0.625 mg of conjugated equine estrogen plus one tablet 2.5 mg of medroxyprogesterone acetate daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: David M. Herrington, MD, MHS, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• 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. Erratum In: Control Clin Trials 2000 Aug;21(4):414.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 1995
• Primary Completion (Actual): January 1, 2001
• Study Completion (Actual): January 1, 2001

Study Registration Dates

• First Submitted: April 26, 2011
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 31, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Atherosclerosis; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Estrogens; Medroxyprogesterone Acetate; Medroxyprogesterone; Estrogens, Conjugated (USP)
• Other Study ID Numbers: U01HL45488

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No