Clinical trial NCT02409680: Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)
Official title: Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Premature Birth
Keywords: Preterm birth
Low dose aspirin
Lead sponsor: NICHD Global Network for Women's and Children's Health
Sponsor class: NETWORK
Collaborators: name: Thomas Jefferson University
name: Jawaharlal Nehru Medical College
First posted: 2015-04-07
Enrollment: 11976
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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)

Primary outcomes:
measure: Incidence of Preterm Birth
timeFrame: At delivery
Secondary outcomes:
measure: Incidence of Hypertensive Disorders of Pregnancy
timeFrame: Evidence of hypertensive disorder during the pregnancy (prior to delivery/birth)
measure: Incidence of Small for Gestational Age (SGA)
timeFrame: At delivery or at Day 42 after delivery
measure: Incidence of Perinatal Mortality
timeFrame: At delivery or at Day 42 after delivery
Other outcomes:
measure: Maternal Outcome 1 - Incidence of Vaginal Bleeding
timeFrame: At delivery or at Day 42 after delivery
measure: Maternal Outcome 2 - Incidence of Antepartum Hemorrhage
timeFrame: At delivery or at Day 42 after delivery
measure: Maternal Outcome 3 - Incidence of Postpartum Hemorrhage
timeFrame: At delivery or at Day 42 after delivery
measure: Maternal Outcome 4 - Incidence of Maternal Mortality
timeFrame: At delivery or at Day 42 after delivery
measure: Maternal Outcome 5 - Incidence of Late Abortion
timeFrame: At delivery or at Day 42 after delivery
measure: Maternal Outcome 6 - Change in Maternal Hemoglobin
timeFrame: At enrollment, 4 weeks post enrollment, and 26-30 weeks GA.
measure: Maternal Outcome 7 - Incidence of Preterm, Preeclampsia
timeFrame: At delivery or at Day 42 after delivery
measure: Fetal Outcome 1 - Incidence of Early Preterm Delivery (<34 Weeks)
timeFrame: At delivery
measure: Fetal Outcome 2 - Incidence of Actual Birth Weight <2500g
timeFrame: At delivery
measure: Fetal Outcome 3 - Incidence of Actual Birth Weight <1500g
timeFrame: At delivery
measure: Fetal Outcome 4 - Incidence of Fetal Loss
timeFrame: At delivery
measure: Fetal Outcome 5 - Incidence of Spontaneous Abortion
timeFrame: At delivery
measure: Fetal Outcome 6 - Incidence of All Stillbirth
timeFrame: At delivery
measure: Fetal Outcome 7 - Incidence of Medical Termination of Pregnancy
timeFrame: At delivery
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Denver
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Kinshasa School of Public Health
city: Guatemala City
country: Guatemala
facility: Institute of Nutrition of Central America and Panama (INCAP)
city: Belgaum
country: India
facility: KLE University's Jawaharlal Nehru Medical College
state: Karnataka
city: Nagpur
country: India
facility: Lata Medical Research Foundation
city: Eldoret
country: Kenya
facility: Moi University School of Medicine
city: Karachi
country: Pakistan
facility: The Aga Khan University
city: Lusaka
country: Zambia
facility: University Teaching Hospital
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Marion Koso-Thomas, MD
role: STUDY_DIRECTOR
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