Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction

June 11, 2021 updated by: Johns Hopkins University

A Randomized Trial of Transplacental Aspirin Therapy for Early Onset Fetal Growth

The purpose of this investigation is to evaluate the ability of maternal aspirin (ASA) therapy to prevent preterm birth for fetal indications prior to 32 weeks gestation in women with early onset Fetal Growth Restriction (FGR). Aspirin is a commonly used medication that blocks blood platelets from clumping. Aspirin crosses the placenta in a dose dependent mode. There is preliminary evidence in smaller studies that aspirin can block fetal platelet clumping and, therefore, slow down the progression of placental disease under specific circumstances. The optimal time for aspirin to work is when the fetus' placental dysfunction is still mild. The goal of this research study is to show if fetuses that receive aspirin through maternal intake at a dose shown to affect fetal platelet aggregation will be less likely to deliver before 32 weeks for fetal deterioration. The outcomes of patients that receive aspirin will be compared to women that receive standard FGR management but do not take any aspirin. The decision if a study participant receives aspirin or not will be randomly picked. Such a research study is called a randomized controlled trial.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Early onset FGR requiring preterm delivery by 32 weeks gestation complicates 1-5% of pregnancies and is an important health problem. Over 60% of children have long-term health consequences after being delivered for early onset FGR. There is no prenatal treatment for fetal growth restriction. The current management of FGR consists of fetal surveillance to detect a decline in the baby's health and deliver when this can be safely done. In a large number of early onset FGR, premature delivery is required to prevent the fetus from becoming more compromised or even dying in the womb.

Placental dysfunction leading to early onset FGR is characterized by changes to the blood vessels of the placenta, leading to a decline in the amount of blood flow to the placenta. The arteries that run in the umbilical cord of the fetus (umbilical arteries) are important for nutrient exchange between the fetal and placental circulation. Many fetuses with early onset FGR have elevated resistance in the blood vessels entering the placenta. This results in decreased blood flow in the umbilical artery (UA). The blood flow in the umbilical artery is evaluated by a specialized ultrasound technique called Doppler ultrasound. Doppler ultrasound of the umbilical arteries examines the blood flow to see if there is evidence of abnormal blood flow into the placenta. When the amount of blood flow at the end of every pulse decreases, it is classified as elevated UA blood flow resistance. When the blood flow briefly pauses at the end of each pulse, this is called absent end-diastolic velocity (AEDV) or UA AEDV. When the blood flow reverses at the end of each pulse, this is called reversed end-diastolic velocity (UA REDV). In fetuses with elevated UA blood flow, the placenta can usually supply enough nutrients and oxygen for at least 9 weeks. After that time, delivery is typically required. The worsening of blood flow to UA AEDV, or even UA REDV, increases the risk for fetal deterioration and preterm birth within the next 2-6 weeks. Approximately, 80% of early onset FGR fetuses progress to UA AEDV, or even UA REDV, and then require delivery by 32 weeks. There is no treatment that can stop this progression which is of critical importance in determining how much time is left for the fetus before delivery will be necessary.

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women at least 18 years old
  • Gestational age between 220/7 to 300/7 weeks
  • Fetal abdominal circumference < 10th percentile
  • Umbilical artery Doppler index elevation > 95th percentile
  • Forward umbilical artery end-diastolic flow
  • Able to understand purpose, risks/benefits, and voluntary nature of study participant

Exclusion Criteria:

  • Multiple pregnancy
  • Currently taking 81 mg aspirin
  • Maternal contraindication to aspirin treatment including allergy
  • Active vaginal bleeding
  • Presence of any physical fetal anomaly
  • Fetal viral infection if diagnosed by the appropriate diagnostic test
  • Fetal chromosomal abnormalities if diagnosed by invasive fetal testing
  • Need for imminent delivery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ASA Group
Receives standard of care and intervention.
Drug: Aspirin
Two tablets daily with dinner
Other Names:
  • acetylsalicylic acid (ASA)
No Intervention: SOC Group
Receives standard of care (SOC), only

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of fetuses delivered for non-reassuring fetal status prior to 32+0 week's gestation
Time Frame: From randomization until birth, up to 38 weeks gestation
To determine the frequency of delivery prior to 32+0 weeks' gestation for abnormal fetal surveillance parameters.
From randomization until birth, up to 38 weeks gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in UA Doppler index
Time Frame: Baseline and weekly, up to 38 weeks gestation
UA Doppler index is assessed at enrollment (baseline) and weekly. Qualitative changes in UA Doppler index are measured as presence, absence or reversal of end-diastolic velocity.
Baseline and weekly, up to 38 weeks gestation
Change in amniotic fluid index (AFI)
Time Frame: Baseline and weekly, up to 38 weeks gestation
Amniotic fluid index, measured with amniotic fluid volume [in centimeters (cm)] will be assessed at enrollment (baseline) and weekly. Oligohydramnios is an AFI ≤ 5 cm or a maximum vertical pocket (MVP) pocket ≤ 2 cm.
Baseline and weekly, up to 38 weeks gestation
Change in fetal heart rate decelerations
Time Frame: Baseline and weekly to bi-weekly, up to 38 weeks gestation
Fetal heart rate decelerations [in milliseconds (ms)] is assessed at enrollment (baseline) and weekly to bi-weekly. Heart rate variability increases with gestational age. After 29 weeks gestation, 4.0 ms and 3.0 ms meet criteria for reduced or very low short-term variation (STV) respectively. Before 29 weeks gestation, an STV <3.5 ms is considered reduced and <2.6 ms as very low.
Baseline and weekly to bi-weekly, up to 38 weeks gestation
Change in biophysical profile score
Time Frame: Baseline and weekly to bi-weekly, up to 38 weeks gestation
Biophysical profile score is assessed at enrollment (baseline) and weekly to bi-weekly. The biophysical profile (BPP) combines a nonstress test (NST) with an ultrasound to evaluate a baby's heart rate, breathing, movements, muscle tone and amniotic fluid level. Each gives a score between 0 and 2 and are added up for a total maximum score of 10. A score of 8 or 10 is considered normal, while a score below 8 usually requires further evaluation or delivery of the baby.
Baseline and weekly to bi-weekly, up to 38 weeks gestation
Gestational age at delivery
Time Frame: At time of birth, up to 38 weeks gestation
Gestational age at delivery measured in weeks.
At time of birth, up to 38 weeks gestation
Birthweight percentile at delivery
Time Frame: At time of birth, up to 38 weeks gestation
Birthweight percentile will be assessed at the time of delivery.
At time of birth, up to 38 weeks gestation
Placental size at delivery
Time Frame: At time of birth, up to 38 weeks gestation
Placental size measured in grams at delivery.
At time of birth, up to 38 weeks gestation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Ahmet A Baschat, Johns Hopkins University
  • Principal Investigator: Ashi R Daftary, MD, Allegheny Health Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 11, 2022

Primary Completion (Anticipated)

June 11, 2023

Study Completion (Anticipated)

June 11, 2023

Study Registration Dates

First Submitted

September 15, 2020

First Submitted That Met QC Criteria

September 15, 2020

First Posted (Actual)

September 21, 2020

Study Record Updates

Last Update Posted (Actual)

June 16, 2021

Last Update Submitted That Met QC Criteria

June 11, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00259253

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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