Official Title

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

    N/A
  • Study Type

    Interventional
  • Study Participants

    11976
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).
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
Study Started
Mar 23
2016
Primary Completion
Apr 11
2019
Study Completion
Apr 11
2019
Results Posted
Sep 08
2021
Last Update
Sep 08
2021

Drug Low dose aspirin

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.

  • Other names: Acetylsalicylic acid (ASA)

Drug Placebo

Placebo

Intervention Arm Active Comparator

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.

Placebo Arm Placebo Comparator

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.

Criteria

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)

Summary

Intervention Arm

Placebo Arm

All Events

Event Type Organ System Event Term Intervention Arm Placebo Arm

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.

Intervention Arm

Placebo Arm

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.

Intervention Arm

Placebo Arm

Incidence of Small for Gestational Age (SGA)

- Small for gestational age (SGA) as defined by the INTERGROWTH-21st standard

Intervention Arm

Placebo Arm

Incidence of Perinatal Mortality

- Incidence of Perinatal Mortality

Intervention Arm

Placebo Arm

Maternal Outcome 3 - Incidence of Postpartum Hemorrhage

- Postpartum hemorrhage

Intervention Arm

Placebo Arm

Maternal Outcome 4 - Incidence of Maternal Mortality

- Incidence of Maternal Mortality

Intervention Arm

Placebo Arm

Maternal Outcome 5 - Incidence of Late Abortion

- Incidence of Late Abortion

Intervention Arm

Placebo Arm

Maternal Outcome 6 - Change in Maternal Hemoglobin

Hemoglobin < 7.0 gm/dl at 26-30 weeks gestation or a drop of 3.5+ gm/dl from screening to 26-30 weeks gestation

Intervention Arm

Placebo Arm

Maternal Outcome 7 - Incidence of Preterm, Preeclampsia

Early preterm delivery (<34 weeks) and hypertensive disorders (i.e.: preeclampsia)

Intervention Arm

Placebo Arm

Fetal Outcome 1 - Incidence of Early Preterm Delivery (<34 Weeks)

- Early preterm delivery (<34 weeks)

Intervention Arm

Placebo Arm

Fetal Outcome 2 - Incidence of Actual Birth Weight <2500g

- Birth weight <2500g

Intervention Arm

Placebo Arm

Fetal Outcome 3 - Incidence of Actual Birth Weight <1500g

- Birth weight <1500g

Intervention Arm

Placebo Arm

Fetal Outcome 4 - Incidence of Fetal Loss

- Incidence of Fetal Loss

Intervention Arm

Placebo Arm

Fetal Outcome 6 - Incidence of All Stillbirth

- Incidence of All stillbirth

Intervention Arm

Placebo Arm

Fetal Outcome 7 - Incidence of Medical Termination of Pregnancy

- Incidence of Medical Termination of Pregnancy

Intervention Arm

Placebo Arm

Fetal Outcome 5 - Incidence of Spontaneous Abortion

- Incidence of Spontaneous Abortion

Intervention Arm

Placebo Arm

Maternal Outcome 1 - Incidence of Vaginal Bleeding

- Vaginal bleeding

Intervention Arm

Placebo Arm

Maternal Outcome 2 - Incidence of Antepartum Hemorrhage

- Antepartum hemorrhage

Intervention Arm

Placebo Arm

Total

11558
Participants

Antenatal care visits

5
visits (Median)
Inter-Quartile Range: 4.0 to 6.0

Maternal body-mass-index

21.0
kg/m^2 (Mean)
Standard Deviation: 3.7

Maternal Height

153.1
cm (Mean)
Standard Deviation: 7.0

Maternal Weight

49.2
kg (Mean)
Standard Deviation: 8.8

Projected gestational age at enrollment

10.1
weeks (Median)
Inter-Quartile Range: 8.6 to 12.0

Race and Ethnicity Not Collected

0
Participants

Age, Customized

Delivery attendant

Delivery location

Delivery mode

Maternal Education

Number of pregnancies

Sex: Female, Male

Site

Overall Study

Intervention Arm

Placebo Arm

Drop/Withdrawal Reasons

Intervention Arm

Placebo Arm