Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)

Study Overview
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Brief Summary
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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
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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

Official Title
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Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)

Conditions
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Premature Birth

Intervention / Treatment
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* Drug: Low dose aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention Arm<br>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. | Drug: Low dose aspirin<br>* 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.<br>* Other names: Acetylsalicylic acid (ASA);|
| Placebo Comparator: Placebo Arm<br>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. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Preterm Birth | 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. | At delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Hypertensive Disorders of Pregnancy | - Hypertensive disorders of pregnancy is defined by the characterization of evidence of a hypertensive disorder, including either preeclampsia or eclampsia occurring during the pregnancy. | Evidence of hypertensive disorder during the pregnancy (prior to delivery/birth) | 
| Incidence of Small for Gestational Age (SGA) | - Small for gestational age (SGA) as defined by the INTERGROWTH-21st standard | At delivery or at Day 42 after delivery | 
| Incidence of Perinatal Mortality | - Incidence of Perinatal Mortality | At delivery or at Day 42 after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm birth, Low dose aspirin