Hormones Inflammation and Thrombosis (HIT2)

The investigators are attempting to determine if the response to aspirin in women is related to the level of estrogen and progesterone that a woman has.

Study Overview

• Status: Terminated
• Conditions: Thrombosis; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Aspirin 81 mg

Detailed Description

Thrombosis plays a significant role in both acute coronary syndromes (ACS) and early saphenous vein graft (SVG) failure. Women with coronary heart disease have higher levels of the inflammatory mediator thromboxane, which is produced by platelets, monocytes, macrophages and the endothelium. Data show that higher levels of urinary thromboxane (UTXB2) are associated with SVG failure 6 months after Coronary Artery Bypass Graft (CABG). Women in the study cohort had higher levels of UTXB2 and higher odds of graft failure when compared to men. The elevated urinary thromboxane seen in the women in our study cohort may represent a marker and/or an etiology of thrombosis.

Are the levels of UTXB2 higher in women due to hormonal differences? In a prior pilot study we investigated whether hormonal levels are associated with changes in urinary thromboxane. We looked at hormonal and urinary thromboxane levels in 48 postmenopausal and 52 premenopausal women. We found that postmenopausal women had higher levels of UTXB2 than did premenopausal women (2495 vs. 2299, p=.02) and that in premenopausal women a higher estrogen/progesterone ratio was associated with the highest levels of urinary thromboxane.

The goal of the current study is to measure the response to seven days of aspirin administration as it relates to urinary thromboxane levels in pre and post-menopausal women. With this study we will be able to examine the change in UTXB2 comparing the premenopausal to post menopausal women. We will also be able to see if the change in UTXB2 in response to aspirin is affected by hormone levels in the premenopausal women. Lastly this study will provide reference data for more far-reaching studies exploring how global changes in hormonal balance (as seen in pregnancy or menopause) or in the level of inflammation (as seen in aging or with Coronary Artery Disease (CAD) risk factors), affect UTXB2 and platelet hyperreactivity.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women age 18-80
2. Signed informed consent.

Exclusion Criteria:

1. History of CAD, Cerebrovascular Accident (CVA) or Peripheral Artery Disease (PAD),
2. On chronic aspirin therapy,
3. On chronic NSAID therapy.
4. Chronic anticoagulation with coumadin,
5. Known thrombocytopenia (Platelet count < 100,000),
6. Pregnancy (self-report),
7. Currently on any type of contraceptive or hormone replacement therapy,
8. Hysterectomy and/or oophorectomy.
9. Recent GI bleeding
10. Bleeding diathesis
11. Chronic Systemic Infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aspirin; The patients are given aspirin 81 mg orally for 7 days.	Drug: Aspirin 81 mg; Aspirin 81 mg orally daily for 7 days; Other Names: ASP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Urinary Thromboxane (UTXB2) in pg/mg Creatinine	Urinary thromboxane (pg/mg creatinine) will be measured in premenopausal and postmenopausal women at baseline and then after taking on aspirin for 7 days.	Baseline
The Change in the Level of UTXB2 in pg/mg Creatinine: Estrogen and Progesterone	Measurement of urinary thromboxane (pg/mg creatinine) in relation to estrogen to progesterone level in premenopausal women on aspirin for 7 days.	baseline to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of UTXB2 in pg/mg Creatinine	Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin	baseline
Relative Change of UTXB2 in pg/mg Creatinine in Response to Aspirin	Comparing premenopausal women to postmenopausal women, the level of urinary thromboxane (pg/mg creatinine) in response to aspirin	change from baseline to 7 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Rhondalyn McLean, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 10, 2013
• First Posted (ESTIMATE): June 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2018
• Last Update Submitted That Met QC Criteria: April 2, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: acute coronary syndrome; women; hormones; clotting
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Inflammation; Thrombosis; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: NA_00079522