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Women's Health Study (WHS): A Randomized Trial of Low-dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer (WHS)

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ClinicalTrials.gov Identifier: NCT00000479
Recruitment Status : Completed
First Posted : October 28, 1999
Results First Posted : June 13, 2012
Last Update Posted : June 15, 2012
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Julie E. Buring, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE October 27, 1999
First Posted Date  ICMJE October 28, 1999
Results First Submitted Date December 5, 2011
Results First Posted Date June 13, 2012
Last Update Posted Date June 15, 2012
Study Start Date  ICMJE September 1992
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2012)
  • Number of Participants With Major Cardiovascular Events (a Combined Endpoint of Nonfatal Myocardial Infarction, Nonfatal Stroke, and Total Cardiovascular Death) [ Time Frame: Average follow-up 10.1 years ]
  • Number of Participants With Cancer, Excluding Nonmelanoma Skin Cancer [ Time Frame: Average follow-up 10.1 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00000479 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Women's Health Study (WHS): A Randomized Trial of Low-dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer
Official Title  ICMJE Women's Health Study of Low-dose Aspirin and Vitamin E in Apparently Healthy Women
Brief Summary The purpose of this study is to evaluate the effects of low-dose aspirin and vitamin E in primary prevention of cardiovascular disease and cancer in apparently healthy women.
Detailed Description

BACKGROUND:

Various doses of aspirin have been shown to be effective in preventing thrombosis or vascular occlusion in several clinical conditions. Short-term studies have documented the efficacy of aspirin in preventing occlusion of saphenous vein bypass grants, preventing myocardial infarction in patients with unstable angina, preventing transient ischemic attacks and stroke in men with cerebral vascular disease, preventing occlusion of injured coronary arteries following transluminal angioplasty and aiding in reducing myocardial infarction and total mortality in patients receiving fibrinolytic therapy. Additionally, aspirin has been effective in the secondary prevention of myocardial infarction in subjects with known coronary artery disease. The results of the Physicians' Health Study, a large-scale primary prevention trial of aspirin in male physicians, have shown a decrease in myocardial infarction, a non-significant increase in cerebral vascular events, and no difference in overall mortality. However, few studies have addressed the efficacy of aspirin in vascular diseases in women, and it is possible that the risk to benefit ratio may be different in women. Specifically, there have been no large primary prevention trials in women, who are at risk of coronary heart disease, especially after menopause.

DESIGN NARRATIVE:

The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design. The WHS is sponsored by both NHBLI (HL080467) and NCI (CA047988). Approximately 1.75 million female health professionals were contacted by mail to determine if they were suitable for inclusion in the study. A three-month run-in phase was performed to screen out those with poor compliance. Randomization, which began in February 1993 and ended in January 1996, was stratified on five-year age groups. A total of 39,876 participants were randomly assigned to either Vitamin E (600 IU every other day) or placebo; and to aspirin (100 mg every other day) or placebo. IN the 2x2 factorial design, women were randomly assigned to active aspirin and placebo vitamin E (n=9,968), placebo aspirin and active vitamin E (n=9,971), active aspirin and active vitamin E (n=9,966), or placebo aspirin and placebo vitamin E (n=9,971). A description of the characteristics of women in these 4 groups is provided in J Women's Health Gend Based Med 2000;9:19-27. In the main analyses, all women on active aspirin (n=19,934) were compared to women on placebo aspirin (n=19,942); and all women on active vitamin E (n=19,937) were compared to women on placebo aspirin (n=19,939).

As part of the initial trial, pre-randomization blood samples from 28,345 participants were frozen and stored for genetic analysis which has been supported by non-federal sources.

The primary endpoint is the reduction of the risk of all important vascular events (a combined endpoint of nonfatal myocardial infarction, nonfatal stroke, and total cardiovascular death) and a decrease in the incidence of total malignant neoplasms of epithelial cell origin. Secondary endpoints are the individual components of the combined endpoints. Compliance is measured by replies to a questionnaire sent out every year. The trial was completed in 2004 and results were published in 2005 (N Engl J Med 2005;352:1293-304; JAMA 2005;294:47-55; JAMA 2005;294:56-65).

Currently, women are being followed on an observational basis.

Study Type  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Cardiovascular Diseases
  • Cerebrovascular Disorders
  • Coronary Disease
  • Heart Diseases
  • Myocardial Infarction
  • Myocardial Ischemia
  • Vascular Diseases
Intervention  ICMJE
  • Drug: Aspirin
    Participants will receive 100 mg of aspirin every other day.
  • Drug: Vitamin E
    Participants will receive 600 IU of vitamin E every other day.
  • Behavioral: Placebo
    Participants will receive placebo.
Study Arms
  • Experimental: 1
    Vitamin E (600 IU every other day) and aspirin (100 mg every other day)
    Interventions:
    • Drug: Aspirin
    • Drug: Vitamin E
  • Experimental: 2
    Vitamin E (600 IU every other day) and placebo
    Interventions:
    • Drug: Vitamin E
    • Behavioral: Placebo
  • Experimental: 3
    Aspirin (100 mg every other day) and placebo
    Interventions:
    • Drug: Aspirin
    • Behavioral: Placebo
  • Placebo Comparator: 4
    Placebo and placebo
    Intervention: Behavioral: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 30, 2008)
39876
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date February 2005
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy women
  • No previous history of cardiovascular disease or cancer
  • No contraindications to aspirin or vitamin E
Sex/Gender
Sexes Eligible for Study: Female
Ages 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00000479
Other Study ID Numbers  ICMJE 69
R01HL043851 ( U.S. NIH Grant/Contract )
HL043851
CA047988
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Julie E. Buring, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Julie Buring Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP