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Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction

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ClinicalTrials.gov Identifier: NCT04557475
Recruitment Status : Withdrawn (We are modifying this trial's protocol and will resubmit a new application at a later date.)
First Posted : September 21, 2020
Last Update Posted : June 16, 2021
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

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

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arms and Interventions
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Arm Intervention/treatment
Experimental: ASA Group
Receives standard of care and intervention.
 Drug: Aspirin
Two tablets daily with dinner
Other Name: acetylsalicylic acid (ASA)
No Intervention: SOC Group
Receives standard of care (SOC), only


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Gestational age at delivery [ Time Frame: At time of birth, up to 38 weeks gestation ]
    Gestational age at delivery measured in weeks.

  6. 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.

  7. Placental size at delivery [ Time Frame: At time of birth, up to 38 weeks gestation ]
    Placental size measured in grams at delivery.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04557475


Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Ahmet A Baschat Johns Hopkins University
Principal Investigator: Ashi R Daftary, MD Allegheny Health Network
More Information
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Publications:

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT04557475    
Other Study ID Numbers: IRB00259253
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Fetal Growth Retardation
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
 Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics