Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)
- Registration Number
- NCT02409680
- Lead Sponsor
- NICHD Global Network for Women's and Children's Health
- Brief Summary
Available data suggest that low dose aspirin may be a safe, widely available and inexpensive intervention that may significantly reduce the risk of preterm birth. However, this possibility needs to be proven in a properly designed randomized controlled trial (RCT) with preterm birth as the primary outcome. Such a clinical trial in a racially, ethnically and geographically diverse population could best be accomplished by the established infrastructure of the Global Network for Women's and Children's Health Research (GN).
- Detailed Description
Background: Preterm birth (PTB) remains the leading cause of neonatal mortality and long term disability throughout the developed and developing world. Though complex in its origins, a growing body of evidence suggests that first trimester administration of low dose aspirin (LDA) holds promise to reduce the rate of PTB substantially.
Hypothesis: The investigators' primary hypothesis is that nulliparous women with no more than two previous first trimester pregnancy losses who are treated with LDA daily beginning between 6 0/7 weeks and 13 6/7 weeks gestational age (GA) through 36 0/7 weeks GA will reduce the risk of preterm birth from all causes.
Study Design Type: Prospective randomized, placebo-controlled, double-blinded multicenter clinical trial (patient level 1:1).
Population: Nulliparous women between the ages of 18 (or local age of majority) and 40 with no more than two previous first trimester pregnancy losses or any second trimester spontaneous pregnancy loss, a singleton pregnancy between 6 0/7 weeks and 13 6/7 weeks GA confirmed by ultrasound, and no contraindications to aspirin. Other medical conditions, such as sickle-cell anemia, may be considered a contraindication per the judgment of the site investigator.
Intervention: Daily administration of low dose (81 mg) aspirin \[also known as acetylsalicylic acid (ASA)\], initiated between 6 0/7 weeks and 13 6/7 weeks GA and continued to 36 0/7 weeks GA compared to an identical appearing placebo. Compliance and outcomes will be assessed biweekly.
Outcomes:
The primary outcome is to determine whether daily LDA initiated between 6 0/7 weeks and 13 6/7 weeks and continued to 36 0/7 weeks reduces the risk of preterm birth (birth prior to 37 0/7 weeks of pregnancy) by 20%. This will be determined based on assessed date of delivery in comparison to the projected estimated date of delivery, independent of whether or not the preterm delivery is indicated or spontaneous.
Secondary outcomes include:
* Preeclampsia and eclampsia (hypertensive disorders of pregnancy)
* Small for gestational age
* Perinatal mortality
Other secondary outcomes of interest are:
Maternal outcomes:
* Vaginal bleeding
* Antepartum hemorrhage
* Postpartum hemorrhage
* Maternal mortality
* Late abortion
* Change in maternal hemoglobin
* Preterm, preeclampsia
Fetal outcomes:
* Preterm birth \<34 0/7 weeks of pregnancy
* Birth weight \<2500g and \<1500g
* Fetal loss
* Spontaneous abortion
* Stillbirth
* Medical termination of pregnancy
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 11976
- Nulliparous women between 18 - 40 years of age. Minors who are ≥ 14 years of age may be enrolled if permitted by the country's ethical guidelines.
- No more than two previous first trimester pregnancy losses
- No medical contraindications to aspirin;
- Single live intrauterine pregnancy (IUP) between 6 0/7 and 13 6/7 weeks GA corroborated by an early dating ultrasound and with presence of a heartbeat.
- Women prescribed daily aspirin for more than 7 days;
- Multiple gestations;
- Fetal anomaly by ultrasound (Note most fetal anomalies are not detectable by ultrasounds done at this early gestation. Subsequent discovery of a fetal anomaly is not viewed as an exclusion.);
- Hemoglobin < 7.0 gm/dl at screening;
- Any other medical conditions that may be considered a contraindication per the judgment of the site investigator (e.g., Lupus, Type 1 Diabetes, or any other known significant disease)
- Blood pressure ≥ 140/90 (Systolic blood pressure ≥ 140 and diastolic ≥ 90 at screening)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Arm Placebo Women will be randomized equally to receive an identical appearing placebo beginning between 6 0/7 weeks and 13 6/7 weeks GA and continuing until 36 0/7 weeks GA or delivery. Intervention Arm Low dose aspirin Women will be randomized equally to receive daily low dose aspirin (LDA) \[also known as acetylsalicylic acid (ASA)\] of 81 mg beginning between 6 0/7 weeks and 13 6/7 weeks GA and continuing until 36 0/7 weeks GA or delivery.
- Primary Outcome Measures
Name Time Method Incidence of Preterm Birth At delivery The primary outcome of this study is incidence of preterm birth, which will be defined as delivery at or after 20 0/7 weeks and prior to 37 0/7 weeks. This will be determined based on actual date of delivery in comparison to the projected estimated due date (EDD), independent of whether or not the preterm delivery is indicated or spontaneous.
- Secondary Outcome Measures
Name Time Method Incidence of Hypertensive Disorders of Pregnancy Evidence of hypertensive disorder during the pregnancy (prior to delivery/birth) - Hypertensive disorders of pregnancy is defined by the characterization of evidence of a hypertensive disorder, including either preeclampsia or eclampsia occurring during the pregnancy.
Incidence of Small for Gestational Age (SGA) At delivery or at Day 42 after delivery - Small for gestational age (SGA) as defined by the INTERGROWTH-21st standard
Incidence of Perinatal Mortality At delivery or at Day 42 after delivery - Incidence of Perinatal Mortality
Trial Locations
- Locations (14)
University of Alabama, Birmingham
🇺🇸Birmingham, Alabama, United States
University of Colorado, Denver
🇺🇸Denver, Colorado, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Boston University
🇺🇸Boston, Massachusetts, United States
Institute of Nutrition of Central America and Panama (INCAP)
🇬🇹Guatemala City, Guatemala
The Aga Khan University
🇵🇰Karachi, Pakistan
KLE University's Jawaharlal Nehru Medical College
🇮🇳Belgaum, Karnataka, India
University of North Carolina, Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Columbia University
🇺🇸New York, New York, United States
Kinshasa School of Public Health
🇨🇩Kinshasa, Congo, The Democratic Republic of the
Lata Medical Research Foundation
🇮🇳Nagpur, India
Moi University School of Medicine
🇰🇪Eldoret, Kenya
University Teaching Hospital
🇿🇲Lusaka, Zambia
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States