Early Prevention of Preeclampsia Study (EPAPP)

Early Prediction and Aspirin for Prevention of Preeclampsia

This is a randomized controlled trial to estimate the efficacy of low dose aspirin for preventing preeclampsia in women identified as high risk. The investigators hypothesize that the risk of preeclampsia in women identified by a first trimester multiparameter predictive model to be at high risk will be significantly reduced by initiating low dose aspirin early in pregnancy.

Study Overview

• Status: Terminated
• Conditions: Preeclampsia
• Intervention / Treatment: Drug: placebo; Drug: Aspirin

Detailed Description

This will be a randomized control trial to estimate the efficacy of low dose aspirin in preventing preeclampsia in women identified in the first trimester to be at high risk. We will also obtain maternal blood, cord blood and placenta specimen for basic science studies to attempt to dissect biological mechanisms of aspirin effects. In addition we will conduct a cost-benefit analysis to determine the cost effectiveness of screening and using aspirin prophylaxis for screen positive women.

Rationale for Design: The randomized control trial is the 'gold standard' of research design. Other designs such as case-control, retrospective cohort and prospective cohort are limited by potential bias and confounding. Randomly assigning subjects to different interventions minimizes selection bias. The random assignment also results in groups that are likely to be similar with regards to important confounding variables. This minimizes confounding by both measured and unmeasured factors. While random allocation does not guarantee the groups will be identical, it does ensure that any differences between them are due to chance alone. Finally, randomization produces groups that are random samples of the population. This permits use of standard statistical tests that are based on probability theory.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Singleton pregnancy undergoing ultrasound examination at 9 0/7 - 14 6/7 weeks
• any one or more factors identified as high risk from the identified risk factors: Chronic hypertension, prepregnancy diabetes mellitus, previous preeclampsia, obesity (BMI >30), bilateral uterine artery notches preeclampsia risk score greater than 6, low PAPP-A ( < 0.52 MoM)

Exclusion Criteria:

• Multiple gestations,
• fetal aneuploidy
• major fetal structural anomaly
• bleeding disorder
• allergy to aspirin
• women already on aspirin or heparin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; Aspirin 81mg one tablet once a day from recruitment until 37 weeks or labor whichever comes first	Drug: Aspirin
Placebo Comparator: placebo; placebo one tablet once a day from recruitment until 37 weeks or labor whichever comes first	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Preeclampsia	Preeclampsia diagnosed per ACOG criteria: Blood pressure greater than 140/90 on 2 occasions 6 hrs apart and significant proteinuria (greater than 300mg in 24hrs).	within 3 months prior to delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With IUGR, Early Preeclampsia, Severe Preeclampsia, Gestational Hypertension, Preterm Birth, Stillbirth, Placental Abruption, Antepartum Hemorrhage, Neonatal Death, NICU Admission, Miscarriage	Intrauterine growth restriction (IUGR) - estimated fetal weight less than 10th percentile early preeclampsia - preeclampsia delivered prior to 34 weeks severe preeclampsia - blood pressure greater then 160/110 gestational hypertension - hypertension without features of preeclampsia preterm birth, stillbirth, placental abruption, antepartum hemorrhage, neonatal death, NICU admission, miscarriage. Statistical significance not reported due to the low recruitment and poor patient compliance.	within 3 months of delivery

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Anthony Odibo, MD, MSCE, Washington University School of Medicine

Publications and helpful links

General Publications

• Odibo AO, Goetzinger KR, Odibo L, Tuuli MG. Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a randomized controlled trial. Ultrasound Obstet Gynecol. 2015 Oct;46(4):414-8. doi: 10.1002/uog.14889. Epub 2015 Aug 31.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 20, 2015
• Study Completion (Actual): July 20, 2015

Study Registration Dates

• First Submitted: March 1, 2012
• First Submitted That Met QC Criteria: March 1, 2012
• First Posted (Estimate): March 7, 2012

Study Record Updates

• Last Update Posted (Actual): June 29, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Aspirin; preeclampsia
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 201112007