Using Placental Pathology to Prevent Recurrent Adverse Pregnancy Outcomes: A Pilot Project

Using Placental Pathology to Prevent Recurrent Adverse Pregnancy Outcomes: A Pilot Project (UPPPP Trial)

The goal of this randomized clinical trial is to evaluate if we can use placental pathology in a prior pregnancy which had an adverse outcome, such as early delivery, stillbirth, a baby born smaller than expected, or severe forms of high blood pressure during pregnancy, to guide treatment in the subsequent pregnancy and reduce risk of recurrent adverse pregnancy events.

The main questions it aims to answer are:

• Whether enoxaparin prevents recurrent adverse pregnancy outcomes among patients with a prior adverse pregnancy outcome that occurred in the setting of maternal vascular malperfusion (MVM).
• If enoxaparin reduces the occurrence or severity of MVM among patients with a prior adverse pregnancy outcome that occurred in the setting of MVM.

Study Overview

• Status: Recruiting
• Conditions: Adverse Pregnancy Outcome
• Intervention / Treatment: Drug: Lovenox 40mg

Detailed Description

In this clinical trial, participants will undergo consent, blood samples will be collected, and participants will be randomized in a 1:1 ratio to the enoxaparin or control groups at their first study visit.

• Participants will return for a study visit within 1 week following randomization.
• If assigned to the enoxaparin, the participant will be asked to take a dose of the enoxaparin once a day (40 mg daily) daily from 12 0/7 weeks and/or the start of enrollment (whichever is later) and continue until 36 weeks gestational age, after which enoxaparin will be discontinued.
• Participants in the control group will have care as usual, with no additional medications.
• During this study, a study team member will collect a blood sample from all participants at 20-24 weeks, 32-34 weeks, and at delivery.
• Participants in the enoxaparin group will have their blood work checked a week after starting medication to ensure that they have no unanticipated side effects.

Researchers will compare the enoxaparin group to the control group to see if enoxaparin prevents or reduces the occurrence or severity of maternal vascular malperfusion (MVM) among patients with a prior adverse pregnancy outcome.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sunitha Suresh; Phone Number: (847) 570-2860; Email: SSuresh@northshore.org
• Study Contact Backup: Name: Kate Honeyfield; Phone Number: 847-570-2243; Email: KHoneyfield@northshore.org

Study Locations

• United States
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Recruiting
      • Northshore University Healthsystem
      • Contact: Sunitha Suresh, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Eligibility Criteria:

Inclusion (must meet all three criteria):

1. Subjects with a prior adverse outcome in a prior pregnancy. Adverse outcome is defined as prior singleton preterm birth ( < 37 weeks), SGA infant (defined as birthweight < 10th percentile), preeclampsia with severe features, or stillbirth (fetal demise after 20 weeks gestation), as certified by an obstetrician
2. Patients with maternal vascular malperfusion on pathology from pregnancy with prior adverse pregnancy outcome, as certified by a perinatal placental pathologist
3. Current singleton pregnancy at <16 6/7 weeks gestational age.

Exclusion Criteria:

1. Anticoagulation planned for current pregnancy (including warfarin, enoxaparin, heparin)
2. Known major fetal anomaly
3. Contraindication to enoxaparin: Specifically active major bleeding, known thrombocytopenia (platelets <100), hypersensitivity to enoxaparin sodium, hypersensitivity to heparin or pork products, hypersensitivity to benzyl alcohol
4. Chronic kidney disease with eGFR< 60
5. Known chronic liver disease with baseline AST/ALT > 3 x upper limit of normal
6. Subjects with mechanical prosthetic heart valves

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enoxaparin Group; Participants in the enoxaparin group will be asked to take a dose of the enoxaparin once a day (40 mg daily) daily from 12 0/7 weeks and/or start of enrollment (whichever is later), and continue until 36 weeks gestational age, after which enoxaparin will be discontinued.	Drug: Lovenox 40mg; Enoxaparin is a blood thinner. It is approved for use in the prevention of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness; inpatient treatment of acute DVT with or without pulmonary embolism; outpatient treatment of acute DVT without pulmonary embolism; Prevention of ischemic complications of unstable angina and non-Q-wave myocardial infarction; treatment of acute ST-segment elevation myocardial infarction(STEMI) managed medically or with subsequent percutaneous coronary intervention. The use of Lovenox has been shown to be safe, and it has also been used widely off-label in pregnancy.; Other Names: Enoxaparin
No Intervention: Control Group; Participants in this group will have standard care as usual, with no additional medications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Adverse Pregnancy outcome	Preeclampsia with severe features, small for gestational age infant, preterm delivery <37 weeks, neonatal death, and maternal death	Enrollment through 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal vascular malperfusion (MVM)	Presence/ absence of MVM on placental pathology	Placenta collected at time of delivery
Preeclampsia with severe features	Defined by clinician	Enrollment through 6 weeks postpartum
Small for gestational age infant	By Fenton criteria	At time of delivery
Preterm delivery < 37 weeks		Assessed at time of delivery
Neonatal Death		Assessed from time of delivery to 6 weeks postpartum
Maternal Death		Assessed from enrollment to 6 weeks postpartum

Collaborators and Investigators

• Sponsor: Endeavor Health
• Investigators: Principal Investigator: Sunitha Suresh, Endeavor Health

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: August 8, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: preterm delivery; Low birth weight; preeclampsia; miscarriage; stillbirth
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: EH22-128

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No