The Effects of Aspirin in Gestation and Reproduction (EAGeR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Enrique Schisterman, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00467363
First received: April 27, 2007
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

The primary objective of the study is to help elucidate the effects of low-dose aspirin in combination with folic acid on the incidence of live births and spontaneous abortions among a group of women who become pregnant compared to a control group.


Condition Intervention
Birth
Spontaneous Abortion
Drug: acetylsalicylic-acid (aspirin)
Dietary Supplement: Folic acid

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Aspirin in Gestation and Reproduction: A Multi-center, Controlled, Double-blind Randomized Trial.

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:
  • Live Birth [ Time Frame: after delivery ] [ Designated as safety issue: No ]
    Live birth was obtained prospectively by maternal report and abstraction from medical records by trained staff .


Secondary Outcome Measures:
  • hCG Recognized Pregnancy [ Time Frame: within 8-weeks of gestation ] [ Designated as safety issue: Yes ]
  • Clinically Recognized Pregnancy [ Time Frame: 8-weeks ] [ Designated as safety issue: Yes ]
  • Early Pregnancy Loss (EPL) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Pregnancy Losses Occurring Less Than 10 Weeks [ Time Frame: less than 10-weeks ] [ Designated as safety issue: Yes ]
  • Fetal Pregnancy Loss [ Time Frame: until 40 weeks ] [ Designated as safety issue: Yes ]
  • Stillbirth [ Time Frame: 40 weeks ] [ Designated as safety issue: Yes ]
  • Ectopic Pregnancy [ Time Frame: within 6 weeks ] [ Designated as safety issue: Yes ]
  • Molar Pregnancy [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Preeclampsia [ Time Frame: until delivery ] [ Designated as safety issue: Yes ]
  • Small for Gestational Age Infant [ Time Frame: until delivery ] [ Designated as safety issue: Yes ]
  • Preterm Birth [ Time Frame: until delivery ] [ Designated as safety issue: Yes ]
  • Abnormal Fetal Testing [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Fetal Intolerance of Labor [ Time Frame: until delivery ] [ Designated as safety issue: Yes ]
  • Abruption [ Time Frame: until delivery ] [ Designated as safety issue: Yes ]

Enrollment: 1228
Study Start Date: June 2007
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Aspirin
81mg of low-dose aspirin plus 400micrograms of folic acid.
Drug: acetylsalicylic-acid (aspirin)
81mg of low-dose aspirin plus 400micrograms of folic acid.
Other Name: aspirin
Placebo Comparator: Placebo
400micrograms of folic acid.
Dietary Supplement: Folic acid
400micrograms of folic acid.

Detailed Description:

Despite the fundamental nature of reproduction, for many it is a process fraught with frustration, inefficiency and imperfections, the effects of which can be severe. Infertility affects 10-15% of couples attempting to conceive. Among all women who conceive, the incidence of spontaneous abortion (SA) has been estimated to be between 15 and 31%, and in many cases the cause is unknown. Additionally, of the four million births yearly in the United States, between 8 and 15% will be born prematurely and experience increased morbidity and mortality as a result. An intervention with even a small absolute effect on any of these outcomes has great implications at the population level due to the large potential attributable benefit.

One such potential intervention is low-dose acetylsalicylic-acid (aspirin). Aspirin has been a primary target of interest because of its anti-inflammatory, vasodilatory and platelet aggregation inhibition properties. To evaluate the effects of low-dose aspirin in combination with folic acid on the incidence of live births and spontaneous abortion, we are conducting a multi-site randomized controlled trial study with two sites and one data coordinating center. Women aged 18-40 currently trying to become pregnant and who have had a single spontaneous abortion in the past year will be eligible for the study. The recruitment goal is 1600 women. Participating women will be randomly assigned to one of two treatment groups. Those randomized to treatment will receive daily low-dose aspirin. Those randomized to placebo will receive daily placebo. Both groups will receive folic acid daily in accordance with recommendations from the U.S. Public Health Service for prevention of birth defects. The duration of treatment regimens (LDA and folic acid or placebo and folic acid) will be 6 menstrual cycles, with those who become pregnant continuing until the end of pregnancy. Monthly urine and blood samples will be collected and questionnaires administered.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women experiencing one or two pregnancy losses at any point in gestation in the past that were not elective termination(s). At least one of these losses must be well documented by one of the following:

    • Sonogram demonstrating anembryonic loss, embryonic loss or fetal death.
    • Histologic confirmation of products of conception that were spontaneously passed per vagina or surgically obtained.
    • Hospital records of fetus delivery.
    • Late menses and positive serum hCG or positive urine hCG documented by hospital or clinic records followed by either a negative hospital/clinic pregnancy test or a decline in urinary hCG level over 3 days.
    • Home pregnancy tests without hCG confirmation from a healthcare provider (either serum or urine) will not be accepted.
  • No more than 5 pregnancies in total including the pregnancy loss(es).*
  • Up to two prior pregnancies that did not end in a loss.*

    *Women may have up to two pregnancies beyond 20 weeks that were not losses, two spontaneous pregnancy losses at any time in the past, and up to one therapeutic or elective termination (two therapeutic or elective terminations if no other pregnancies). Ectopic and molar pregnancies would, for the purpose of enrollment, be considered in the same category as therapeutic termination pregnancies. Women with more than two live births or those with more than two losses, regardless of the week of gestation of the loss, are excluded.

  • Presence of intact tubes (both), ovaries (both), and uterus.
  • Between 18 and 40 years of age at time of baseline visit.
  • Regular menstrual periods between 21 - 42 days in length (within the last 12 months). Regular menstrual periods are defined as no more than an 8-day difference between the woman's shortest and longest cycle.
  • No more than one missed menses in the past 12 months (other than those missed due to pregnancy or breastfeeding).
  • Actively trying to conceive with a male partner and not using contraception by the baseline visit.
  • Not currently pregnant at the baseline or randomization visits.
  • Ability and willingness to give informed consent.
  • Willingness to be randomized and to take daily study pills for 6 months to a possible 15 months

Exclusions Criteria:

  • Known allergies to aspirin or non-steroidal anti-inflammatory agents.
  • Clinical indication for anticoagulant therapy. These include prior or current thrombosis, antiphospholipid syndrome (APS) or known major thrombophilia.
  • Clinical indication for chronic use of NSAIDs such as rheumatoid arthritis.
  • Indication for additional folic acid supplementation, such as prior infant with neural tube defect (NTD), seizure disorder.
  • Medical contraindication to aspirin therapy. These include uncontrolled asthma, nasal polyps, bleeding disorders, or history of gastrointestinal ulcer.
  • Presence of major medical disorders (regardless of severity). These include diabetes, hypertension, systemic lupus erythematosus (SLE), untreated or active cancer (any cancer in remission or non-melanoma skin cancer is not included in the exclusion criteria), liver disease, renal disease, rheumatoid arthritis, cardiac disease, pulmonary disease other than mild asthma, neurologic disease requiring medical treatment, uncontrolled hypothyroidism, uncontrolled seizure disorder. Untreated vitamin B12 deficiency, severe anemia (Hct < 30%), hemophilia, gout, nasal polyps, among others.
  • Currently undergoing/planned use of assisted reproductive techniques during trial (IVF; IUI; Clomid).
  • History of infertility or sub-fertility. This includes any of the following:

    • No conception after ≥ 1 year of unprotected intercourse and actively trying to conceive.
    • Any prior medical treatment for infertility.
    • Prior treatment for known pelvic inflammatory disease.
    • Known male infertility or sperm abnormality (current partner).
    • Known tubal occlusion, anovulation, uterine abnormality, or endometriosis stage III or IV.
    • History of polycystic ovarian syndrome.
  • Presence of unstable mental disorder. These include bipolar illness, schizophrenia, uncontrolled depression, uncontrolled anxiety disorder.
  • Known current or recent alcohol abuse or illicit drug use.
  • Current diagnosis of sexually transmitted infection (STI) (temporary exclusion)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00467363

Locations
United States, Colorado
University of Colorado, Denver School of Medicine, Department of Obstetrics and Gynecology
Denver, Colorado, United States, 80045
United States, New York
Women's Health Research Center, Department of Social and Preventive Medicine, University at Buffalo
Buffalo, New York, United States, 14260
United States, Pennsylvania
Moses Taylor Hospital
Scranton, Pennsylvania, United States, 18510
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Investigators
Principal Investigator: Enrique F Schisterman, PhD Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Jean Wactawski-Wende, PhD University at Buffalo
Principal Investigator: Robert Silver, MD University of Utah
Principal Investigator: Noya Galai, PhD University of Haifa
Principal Investigator: Janet Townsend, M.D. The Commonwealth Medical College
Principal Investigator: Anne Lynch, M.D. University of Colorado, Denver
  More Information

Additional Information:
No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Enrique Schisterman, Chief and Senior Investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00467363     History of Changes
Other Study ID Numbers: EAGeR
Study First Received: April 27, 2007
Results First Received: April 10, 2014
Last Updated: April 10, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Abortion, Spontaneous
Pregnancy Complications
Aspirin
Folic Acid
Vitamin B Complex
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Hematinics
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 18, 2014