Clincosm LogoSign in Get a demo

Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction

Sponsor
Johns Hopkins University (Other)
Overall Status
Withdrawn
CT.gov ID
NCT04557475
Collaborator
(none)
0
Enrollment
2
Arms
12
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Two Group AssignmentTwo Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Trial of Transplacental Aspirin Therapy for Early Onset Fetal Growth
Anticipated Study Start Date :
Jun 11, 2022
Anticipated Primary Completion Date :
Jun 11, 2023
Anticipated Study Completion Date :
Jun 11, 2023

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Number of fetuses delivered for non-reassuring fetal status prior to 32+0 week's gestation [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.

    Secondary Outcome Measures

    1. Change in UA Doppler index [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.

    2. Change in amniotic fluid index (AFI) [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.

    3. Change in fetal heart rate decelerations [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.

    4. Change in biophysical profile score [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.

    5. Gestational age at delivery [At time of birth, up to 38 weeks gestation]

      Gestational age at delivery measured in weeks.

    6. Birthweight percentile at delivery [At time of birth, up to 38 weeks gestation]

      Birthweight percentile will be assessed at the time of delivery.

    7. Placental size at delivery [At time of birth, up to 38 weeks gestation]

      Placental size measured in grams at delivery.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Johns Hopkins University

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT04557475
    Other Study ID Numbers:
    • IRB00259253
    First Posted:
    Sep 21, 2020
    Last Update Posted:
    Jun 16, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Johns Hopkins University
    Maternal Aspirin Therapy
    Additional relevant MeSH terms:
    Fetal Growth Retardation
    Aspirin

    Study Results

    No Results Posted as of Jun 16, 2021