Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study

Myocardial Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00600106
• Other study ID #: 9260
• Secondary ID: IRB#0505140
• Status: Completed
• Phase: N/A
• Start date: December 1999
• Est. completion date: March 2010

Study information

• Verified date: April 2019
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

See Brief Summary above.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2010
• Est. primary completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• 1/10 NA/EE
Hormone replacement therapy with 1 mg norethindrone/10 mcg thinyl estradiol (1/10 NA/EE)
• Placebo
1 mg placebo

Locations

Country	Name	City	State
United States	Cedars-Sinai Women's Heart Center, 8631 W. 3rd St, Suite 740	Los Angeles	California

Sponsors (7)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	Allegheny University, Johns Hopkins University, Parke-Davis, University of Alabama at Birmingham, University of Florida, University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (44)

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* Note: There are 44 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inducible Myocardial Ischemia	Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (?) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.	Baseline
Primary	Endothelial Dysfunction (FMD)	Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of endothelial dysfunction.; Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].	Baseline
Primary	Endothelial Dysfunction (FMD)	Endothelial dysfunction refers to altered vasoactive, anticoagulant, and anti-inflammatory properties of endothelium, and dysregulated vascular growth remodeling that results from a loss of nitric oxide (NO) bioactivity in the endothelium. Brachial Artery Reactivity Testing (BART), high-frequency ultrasonographic imaging of the brachial artery, evaluates flow-mediated vasodilation (FMD), an endothelium-dependent function. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function.; Flow-mediated vasodilation is typically expressed as the change in post-stimulus diameter as a percentage of the baseline diameter [diameter after cuff deflation - baseline diameter / baseline diameter) x 100].	12 weeks
Primary	Inducible Myocardial Ischemia	Inducible myocardial ischemia measured by P-31 gated magnetic resonance cardiac spectroscopy (MRS) is reported as change (?) in PCr/ATP ratio, with isometric submaximal handgrip stress. PCr/ATP ratio defined as (stress-[average of rest and recovery periods]) / average of rest and recover periods X 100, and expressed as % mean ± SD. For this trial, myocardial ischemia was pre-specified as a fall in quantitative PCR/ATP ratio >20% from rest, and a lower value is considered indicative of greater ischemia.	12 weeks
Secondary	Physical Functional Disability - Functional Capacity (METs)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on.	Baseline
Secondary	Quality of Life - Menopause Symptoms	Quality of life assessed by menopausal symptoms and psychological questionnaires	Baseline
Secondary	Quality of Life - Menopause Symptoms	Quality of life assessed by menopausal symptoms and psychological questionnaires	12 weeks
Secondary	Quality of Life - Health Survey	Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.; Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline
Secondary	Quality of Life - Health Survey	Quality of life assessed by cardiac symptoms and psychological questionnaires (SF 36 scale - Short Form Health Survey) The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.; Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	12 weeks
Secondary	Physical Functional Disability - Functional Capacity (METs)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain. A MET is defined as the resting metabolic rate, that is, the amount or oxygen consumet at rest, sitting quietly in a chair, approximately 3.5 ml O2 / kg / min (1.2 kcallmin for a 70-kg person). As such, work at METs requires twice the resting metabolism or 7.0 ml O2/kg/min, and so on.	Exit at 12 weeks
Secondary	Physical Functional Disability - Functional Capacity (Metabolism Equivalents)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.	Baseline
Secondary	Physical Functional Disability - Functional Capacity (Metabolism Equivalents)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.	Exit (12 weeks)
Secondary	Physical Functional Disability - Functional Capacity (Exercise Induced ST Segment Depression)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.; In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point).	Baseline
Secondary	Physical Functional Disability - Functional Capacity (Stress Induced ST Segment Depression)	Physical functional disability measured by exercise stress testing. Functional capacity was measured as metabolism equivalents (METs), exercise duration, and exercise-induced chest pain.; In electrocardiography, the ST segment connects the QRS complex and the T wave and has duration of 80 to 120 ms. It should be essentially level with the PR and TP segment. The normal ST segment has a slight upward concavity. Flat, downsloping, or depressed ST segment may indicate coronary ishcemia. Positive treadmill exercise stress test (>1.0 mm horizontal / downsloping or >1.5 upsloping ST segment depression measured 0.08 msec after the J point).	Exit (12 weeks)