Clinical trial NCT00600106: Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study
Official title: WISE Ancillary Study Data Analyses: Efficacy of Hormone Replacement on Myocardial Ischemia in Postmenopausal Women With Normal/Minimal Coronary Artery Disease: Data Analysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myocardial Ischemia
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Parke-Davis
name: University of Pittsburgh
name: University of Florida
name: Allegheny University
name: University of Alabama at Birmingham
name: Johns Hopkins University
First posted: 2008-01-24
Enrollment: 37
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of the main trial was to evaluate the effect of low dose hormone replacement therapy with 1 mg norethindrone/10mcg ethinyl estradiol in postmenopausal women with a history of chest discomfort, myocardial ischemia and no obstructive CAD. For the purposes of this study as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; glucose, insulin and HOMA core lab analyses; exercise stress test/Holter monitor core lab analyses; brachial artery reactivity test core lab analyses; full study data analyses for manuscript preparation and the writing and submission and publication of manuscript.

The main trial duration: December 1999 - May 2003.

The ancillary data analysis project duration: April 2006 - March 2010.

Detailed description: See Brief Summary above.

Eligibility criteria: Inclusion Criteria

* Postmenopausal WISE and nonWISE study participants
* Normal/minimally diseased coronary arteries (\<50% luminal diameter stenosis in all epicardial coronary arteries) within 36 months of ancillary study entry and no intercurrent MI, PTCA, CABG
* Any one (or multiple) of the following criteria suggestive of myocardial ischemia within 36 months of ancillary study entry:

  1. Abnormal P-31 magnetic resonance spectroscopy (a fall in quantitative PCr/ATP ratio \>15% from control) performed at a WISE or nonWISE site
  2. Positive exercise stress test (\> or = 1mm horizontal or downsloping, or \> or =1.5mm upsloping ST segment depression measured 0.08 msec after the J point), performed and/or interpretated by a WISE or WISE ancillary ancillary trial investigator
  3. Reversible stress radionuclide perfusion defect \> equivocal and not attributable to breast/imaging artifact. performed as part of the WISE protocol
  4. Coronary artery flow reserve \<2.25 performed. as part of using the WISE protocol
* No contraindications to 12 weeks of FemHRT or hormone replacement therapy
* Normal mammogram and pelvic exam (including PAP smear for those with an intact uterus) within 12 months of study entry
* Documented normal liver function testing (SGOT) within 3 months of study entry.

Exclusion Criteria

* Documented myocardial infarction, coronary artery bypass surgery or mechanical revascularization
* Systolic blood pressure \>200 mmHg or diastolic blood pressure \>105 mmHg
* LDL-cholesterol \>190 mg/dl, triglycerides \> or = 300 mg/dl
* Clinically significant hepatic or renal dysfunction (SGOT more than 1.2 times normal at baseline, serum creatinine \>2)
* Uncontrolled diabetes mellitus (FBS \> or = 225 mg/dl) or new onset diabetes until stabilized
* Clinically significant valvular heart disease, dilated cardiomyopathy, or congestive heart failure (NYHA Class IV or severe Class III)
* Currently on hormone replacement therapy and unwilling/unable to withdraw treatment prior to study, (participants are eligible for study entry 4-8 weeks following hormone replacement therapy withdrawal, at the discretion of the WISE ancillary trial Principal Investigator)
* Previous breast cancer, mammogram suggestive of cancer, or endometrial cancer without hysterectomy
* Abnormal uterine bleeding or abnormal Pap smear (SIL I, II or III, carcinoma in situ, or cancer)
* Previous deep venous thrombosis, pulmonary embolism, or other thromboembolic disorder.
* Alcoholism or drug abuse
* Participation in any other investigational drug or device study

Women with elevated diastolic (\> or = 90 mm Hg) or systolic (\> or = 140 mm Hg) blood pressure, LDL-cholesterol (\> or = 160 mg/dl), fasting blood sugar (\> or = 130 mg/dl) and women who smoke cigarettes will be told their risk factor levels and referred for evaluation and treatment by their private physician.

Primary outcomes:
measure: Inducible Myocardial Ischemia
timeFrame: Baseline
measure: Endothelial Dysfunction (FMD)
timeFrame: Baseline
measure: Endothelial Dysfunction (FMD)
timeFrame: 12 weeks
measure: Inducible Myocardial Ischemia
timeFrame: 12 weeks
Secondary outcomes:
measure: Physical Functional Disability - Functional Capacity (METs)
timeFrame: Baseline
measure: Quality of Life - Menopause Symptoms
timeFrame: Baseline
measure: Quality of Life - Menopause Symptoms
timeFrame: 12 weeks
measure: Quality of Life - Health Survey
timeFrame: Baseline
measure: Quality of Life - Health Survey
timeFrame: 12 weeks
measure: Physical Functional Disability - Functional Capacity (METs)
timeFrame: Exit at 12 weeks
measure: Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
timeFrame: Baseline
measure: Physical Functional Disability - Functional Capacity (Metabolism Equivalents)
timeFrame: Exit (12 weeks)
measure: Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression)
timeFrame: Baseline
measure: Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression)
timeFrame: Exit (12 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Women's Heart Center, 8631 W. 3rd St, Suite 740
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: C. Noel Bairey Merz, MD
role: STUDY_CHAIR
affiliation: University of Florida
name: Carl Pepine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Steve Reis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Allegheny University of the Health Sciences
name: Nathaniel Reichek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: William Rogers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Vijay Misra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Robert B Weiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Sheryl Kelsey, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Health (WISE Project Officer)
name: George Sopko, MD
role: STUDY_DIRECTOR
affiliation: Parke-Davis
name: James Symons, PhD
role: STUDY_DIRECTOR
affiliation: Parke-Davis
name: Connie McLaughlin, PharmD
role: STUDY_DIRECTOR
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