Estrogen Replacement to Reduce Risk of Neurologic Injury After Coronary Artery Bypass Graft Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00123539
Recruitment Status : Terminated (DSMB stopped the study based on conclusion of likely futility of treatment on the primary outcome.)
First Posted : July 25, 2005
Last Update Posted : July 29, 2016
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary:
The purpose of this study is to test whether perioperative estrogen replacement in postmenopausal women reduces the risk for neurologic injury after coronary artery bypass graft (CABG) surgery.

Condition or disease Intervention/treatment Phase
Coronary Disease Cardiovascular Diseases Heart Diseases Neurologic Manifestations Drug: Estrogen Replacement Therapy Procedure: Surgery Not Applicable

Detailed Description:


Women undergoing CABG surgery have a higher operative mortality rate, longer hospitalizations, and higher hospital costs compared with men. A large proportion of this excess morbidity and mortality of surgery for women is due to perioperative neurologic injury. Estrogen has been consistently shown to reduce the extent of neurologic injury in a variety of in vitro and animal experimental stroke models. These data together strongly suggest that the higher risk for perioperative neurologic complications for elderly women may relate to their estrogen deficient state.


This randomized, placebo controlled study will test the hypothesis that perioperative estrogen replacement in postmenopausal women reduces the risk for neurologic injury after CABG surgery. Three hundred thirty-four women undergoing CABG surgery will be prospectively randomized to receive either 17 beta-estradiol or placebo in a double-blind fashion beginning the day before surgery and continuing for 5 days after surgery. Patients will be assessed for neurocognitive dysfunction, which is the most common manifestation of neurologic injury from cardiac surgery. Neurocognitive testing will be performed 1 to 2 days before surgery, 4 to 6 weeks postoperatively, and 6 months after surgery. The primary endpoint will be neurocognitive function 4 to 6 weeks after surgery for women who received 17 beta- estradiol compared with placebo perioperatively. The trial will also evaluate the importance of postoperative cognitive decline on measures of cognitive function and quality of life 6 months after surgery, and whether perioperative 17 beta-estradiol treatment improves these outcomes.

Study Type : Interventional  (Clinical Trial)
Enrollment : 334 participants
Allocation: Randomized
Masking: Double
Primary Purpose: Prevention
Official Title: Estradiol for Neurocognitive Dysfunction After CABG
Study Start Date : June 2001
Actual Study Completion Date : August 2005

Resource links provided by the National Library of Medicine

Drug Information available for: Estrogens

Primary Outcome Measures :
  1. Neurocognitive function (measured 4 to 6 weeks after surgery)
  2. Cognitive function
  3. Quality of life (measured 6 months after surgery)

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients whose scheduled procedure is CABG surgery OR
  • Patients whose scheduled procedure is isolated aortic surgery OR
  • Patients whose scheduled procedure is mitral valve surgery OR
  • Patients whose scheduled procedure is CABG combined with aortic or mitral valve surgery

Exclusion Criteria:

  • Patients having re-operations
  • Patients having combined carotid endarterectomy with CABG surgery
  • Patients having CABG with tricuspid valve surgery
  • Patients having mitral and aortic valvular surgery (with or without CABG surgery)
  • Elevation of liver function test before surgery or creatinine before surgery greater than 2 mg/dl
  • Emergency surgery
  • Severe cognitive impairment before surgery as indicated by clinical history and/or a score greater than 12 on the Short Blessed Dementia Screening Test (see d11)
  • Inability to attend outpatient visits
  • A history of venous thromboembolism
  • Unexplained vaginal bleeding
  • A history of breast cancer or personal history of endometrial cancer in the absence of hysterectomy
  • Estrogen use within 6 months of the surgery
  • Patient refusal to participate
  • Inability to speak and read English or visual impairment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00123539

United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Charles W. Hogue, Jr., MD Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Charles W. Hogue, MD, The Johns Hopkins Medical Institutions Identifier: NCT00123539     History of Changes
Other Study ID Numbers: 237
R01HL064600 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2005    Key Record Dates
Last Update Posted: July 29, 2016
Last Verified: December 2007

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Coronary Disease
Coronary Artery Disease
Neurologic Manifestations
Myocardial Ischemia
Vascular Diseases
Arterial Occlusive Diseases
Nervous System Diseases
Signs and Symptoms
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs