Heparin Prophylaxis Dosing for Antepartum Hospitalizations (HEPDOSE)

• ClinicalTrials.gov Identifier: NCT04635839
• Recruitment Status: Completed
• First Posted: November 19, 2020
• Results First Posted: April 28, 2023
• Last Update Posted: April 28, 2023
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Thalia Wong, MD, University of California, Los Angeles

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pregnancy Related; Antepartum DVT	Drug: Standard Dose of Unfractionated Heparin; Drug: Gestational Age-Based Dose of Unfractionated Heparin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Randomized Control Trial of Unfractionated Heparin Thromboprophylaxis Dosing for Antepartum Hospitalizations
• Actual Study Start Date: December 15, 2020
• Actual Primary Completion Date: March 31, 2022
• Actual Study Completion Date: May 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Elevated Serum Activated Partial Thromboplastin Time Above the Normal Range (> 36.2 Seconds). [ Time Frame: Collected 6 hours after unfractionated heparin dose until patient was taken of unfractionated heparin, an average of 1 week ]
   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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90095

Sponsors and Collaborators

University of California, Los Angeles

  Study Documents (Full-Text)

Documents provided by Thalia Wong, MD, University of California, Los Angeles:

Study Protocol  [PDF] November 4, 2020

Statistical Analysis Plan  [PDF] June 27, 2022

Informed Consent Form  [PDF] October 19, 2021

More Information

• Responsible Party: Thalia Wong, MD, Co-Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT04635839
• Other Study ID Numbers: 20-001799
• First Posted: November 19, 2020
• Results First Posted: April 28, 2023
• Last Update Posted: April 28, 2023
• Last Verified: April 2023

• 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

Keywords provided by Thalia Wong, MD, University of California, Los Angeles:

Thromboprophylaxis; Antepartum admission; Heparin

Additional relevant MeSH terms:

Heparin; Calcium heparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action