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

Premature Birth Clinical Trial

— ASPIRIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02409680
• Other study ID #: CP ASPIRIN
• Status: Completed
• Phase: N/A
• Start date: March 23, 2016
• Est. completion date: April 11, 2019

Study information

• Verified date: August 2021
• Source: NICHD Global Network for Women's and Children's Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 11976
• Est. completion date: April 11, 2019
• Est. primary completion date: April 11, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Premature Birth

Intervention

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.
• Placebo
Placebo

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Kinshasa School of Public Health	Kinshasa
Guatemala	Institute of Nutrition of Central America and Panama (INCAP)	Guatemala City
India	KLE University's Jawaharlal Nehru Medical College	Belgaum	Karnataka
India	Lata Medical Research Foundation	Nagpur
Kenya	Moi University School of Medicine	Eldoret
Pakistan	The Aga Khan University	Karachi
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Boston University	Boston	Massachusetts
United States	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina
United States	University of Colorado, Denver	Denver	Colorado
United States	Indiana University	Indianapolis	Indiana
United States	Columbia University	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
Zambia	University Teaching Hospital	Lusaka

Sponsors (3)

Lead Sponsor	Collaborator
NICHD Global Network for Women's and Children's Health	Jawaharlal Nehru Medical College, Thomas Jefferson University

Countries where clinical trial is conducted

United States,  Zambia,  Congo, The Democratic Republic of the,  Guatemala,  India,  Kenya,  Pakistan, 

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* Note: There are 63 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal Outcome 1 - Incidence of Vaginal Bleeding	- Vaginal bleeding	At delivery or at Day 42 after delivery
Other	Maternal Outcome 2 - Incidence of Antepartum Hemorrhage	- Antepartum hemorrhage	At delivery or at Day 42 after delivery
Other	Maternal Outcome 3 - Incidence of Postpartum Hemorrhage	- Postpartum hemorrhage	At delivery or at Day 42 after delivery
Other	Maternal Outcome 4 - Incidence of Maternal Mortality	- Incidence of Maternal Mortality	At delivery or at Day 42 after delivery
Other	Maternal Outcome 5 - Incidence of Late Abortion	- Incidence of Late Abortion	At delivery or at Day 42 after delivery
Other	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	At enrollment, 4 weeks post enrollment, and 26-30 weeks GA.
Other	Maternal Outcome 7 - Incidence of Preterm, Preeclampsia	Early preterm delivery (<34 weeks) and hypertensive disorders (i.e.: preeclampsia)	At delivery or at Day 42 after delivery
Other	Fetal Outcome 1 - Incidence of Early Preterm Delivery (<34 Weeks)	- Early preterm delivery (<34 weeks)	At delivery
Other	Fetal Outcome 2 - Incidence of Actual Birth Weight <2500g	- Birth weight <2500g	At delivery
Other	Fetal Outcome 3 - Incidence of Actual Birth Weight <1500g	- Birth weight <1500g	At delivery
Other	Fetal Outcome 4 - Incidence of Fetal Loss	- Incidence of Fetal Loss	At delivery
Other	Fetal Outcome 5 - Incidence of Spontaneous Abortion	- Incidence of Spontaneous Abortion	At delivery
Other	Fetal Outcome 6 - Incidence of All Stillbirth	- Incidence of All stillbirth	At delivery
Other	Fetal Outcome 7 - Incidence of Medical Termination of Pregnancy	- Incidence of Medical Termination of Pregnancy	At delivery
Primary	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	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)
Secondary	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
Secondary	Incidence of Perinatal Mortality	- Incidence of Perinatal Mortality	At delivery or at Day 42 after delivery