Heparin Prophylaxis Dosing for Antepartum Hospitalizations (HEPDOSE)

Randomized Control Trial of Unfractionated Heparin Thromboprophylaxis Dosing for Antepartum Hospitalizations

This study is a randomized control trial to compare gestational age-based dosing with standard dosing of unfractionated heparin for thromboprophylaxis of hospitalized antepartum patients. The investigators aim to determine the effect of dosing on receipt of neuraxial anesthesia and pregnancy outcomes and evaluate the pharmacokinetics and pharmacodynamics of unfractionated heparin in pregnancy.

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Antepartum DVT
• Intervention / Treatment: Drug: Standard Dose of Unfractionated Heparin; Drug: Gestational Age-Based Dose of Unfractionated Heparin

Detailed Description

Venous thromboembolism is one of the leading causes of maternal morbidity and mortality, and antepartum hospitalizations place pregnant patients at an even higher risk of developing thromboembolism. As a result, there is an increased emphasis on administering pharmacologic thromboprophylaxis for antepartum patients with prolonged hospitalizations. Previously, standard dosing of unfractionated heparin was widely adopted for thromboprophylaxis in the pregnant population. However, due to a suspected altered metabolism of unfractionated heparin in pregnancy resulting in a decrease response, the American College of Obstetricians and Gynecologists (ACOG) currently recommends considering gestational age-based dosing for unfractionated heparin for thromboprophylaxis in pregnancy with standard dosing as an alternative option. The data supporting altered dosing is very limited. In addition, increased dosing of heparin may result in challenges in anesthetic management, potentially limiting the receipt of neuraxial anesthesia resulting in increased need for general anesthesia associated with both increased maternal and fetal risks. The potential effects of higher prophylactic unfractionated heparin dosing in pregnant patients need to be further explored before being widely adopted for inpatient antepartum thromboprophylaxis. The investigators propose this study to provide a direct comparison of gestational age-based unfractionated heparin dosing to standard dosing of unfractionated heparin for pharmacologic thromboprophylaxis of hospitalized antepartum patients.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• At least 18 years of age
• Speak English or Spanish
• Antepartum admission for at least 72 hours at Ronald Reagan UCLA Medical Center
• Provides informed consent for study participation

Exclusion Criteria:

• Active or threatened antenatal bleeding
• Disseminated intravascular coagulation
• Risk of imminent delivery (delivery within 12 hours)
• Thrombocytopenia (platelet count < 100 x 109)
• Elevated baseline aPTT (> 36.2 seconds)
• Concern for hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome
• Congenital bleeding disorders (hemophilias)
• Receiving therapeutic or prophylactic anticoagulation (unfractionated heparin, low molecular weight heparin, oral anticoagulants) for alternative indication (e.g., acquired or inherited thrombophilia, history of VTE)
• History of heparin-induced thrombocytopenia (HIT)
• SARS-CoV-2 positive
• Cognitive impairment, psychiatric instability, or language barriers that limit their ability to provide informed consent
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Dosing; Standard dose of unfractionated heparin	Drug: Standard Dose of Unfractionated Heparin; 5,000 units subcutaneous unfractionated heparin every 12 hours
Active Comparator: Gestational Age-Based Dosing; Dose of unfractionated heparin based on trimester of pregnancy	Drug: Gestational Age-Based Dose of Unfractionated Heparin; First trimester (< 14 weeks of gestation): 5,000 units subcutaneous unfractionated heparin every 12 hours; Second trimester (14-28 weeks of gestation): 7,500 units subcutaneous unfractionated heparin every 12 hours; Third trimester (> 28 weeks of gestation): 10,000 units subcutaneous unfractionated heparin every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Elevated Serum Activated Partial Thromboplastin Time Above the Normal Range (> 36.2 Seconds).	Surrogate marker for whether or not the patient would be eligible for neuraxial anesthesia based on guidelines for neuraxial anesthesia in pregnant women receiving VTE prophylaxis	Collected 6 hours after unfractionated heparin dose until patient was taken of unfractionated heparin, an average of 1 week

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Diagnosed With Venous Thromboembolism (Pulmonary Embolism and/or Deep Venous Thromboembolism)	Assessed throughout hospitalization, an average length of 8 days, until 6 weeks after delivery
Number of Participants Who Did Not Receive or Had a Delay of Neuraxial Anesthesia Due to Unfractionated Heparin	Assessed at time of delivery
Number of Participants That Received General Anesthesia	Assessed at time of delivery
Number of Participants That Had a Delay in Timing of Delivery Due to Unfractionated Heparin	Assessed at time of delivery
Maximum Anti-Factor Xa Level Measured	Collected 6 hours after unfractionated heparin dose until patient was taken of unfractionated heparin, an average of 1 week
Mode of Delivery	Assessed at time of delivery
Estimated Blood Loss From Delivery	Assessed at time of delivery
Number of Participants That Received a Blood Transfusion	From time of delivery until 6 weeks after delivery
Maximum Activated Partial Thromboplastin Clotting Time Levels Measured	Collected 6 hours after unfractionated heparin dose until patient was taken of unfractionated heparin, an average of 1 week

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Thromboprophylaxis; Heparin; Antepartum admission
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 20-001799

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