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

Tracking Information

• First Submitted Date: November 9, 2020
• First Posted Date: November 19, 2020
• Results First Submitted Date: February 7, 2023
• Results First Posted Date: April 28, 2023
• Last Update Posted Date: April 28, 2023
• Actual Study Start Date: December 15, 2020
• Actual Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2023)

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

Original Primary Outcome Measures (submitted: November 13, 2020)

Elevated serum aPTT value above the normal range (> 36.2 seconds). [ Time Frame: From date of randomization through study completion, average 4 weeks ]

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

Current Secondary Outcome Measures (submitted: March 15, 2023)

• 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 ]
• 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 ]
• Number of Participants That Received General Anesthesia [ Time Frame: Assessed at time of delivery ]
• Number of Participants That Had a Delay in Timing of Delivery Due to Unfractionated Heparin [ Time Frame: Assessed at time of delivery ]
• 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 ]
• Mode of Delivery [ Time Frame: Assessed at time of delivery ]
• Estimated Blood Loss From Delivery [ Time Frame: Assessed at time of delivery ]
• Number of Participants That Received a Blood Transfusion [ Time Frame: From time of delivery until 6 weeks after delivery ]
• 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 ]

Original Secondary Outcome Measures (submitted: November 13, 2020)

• Diagnosis of venous thromboembolism (pulmonary embolism and/or deep venous thromboembolism) [ Time Frame: From date of randomization up to 6 weeks postpartum ]
• Nonreceipt or delay of neuraxial anesthesia due to unfractionated heparin [ Time Frame: From date of randomization through study completion, average 4 weeks ]
• Receipt of general anesthesia due to unfractionated heparin [ Time Frame: From date of randomization through study completion, average 4 weeks ]
• Delay in timing of delivery due to unfractionated heparin [ Time Frame: From date of randomization through study completion, average 4 weeks ]
• Anti-Xa levels [ Time Frame: From date of randomization through study completion, average 4 weeks ]
• Number of times adjustment in unfractionated heparin dose made [ Time Frame: From date of randomization through study completion, average 4 weeks ]
• Mode of delivery [ Time Frame: From date of randomization until date of delivery ]
• Estimated blood loss from delivery [ Time Frame: From date of randomization until 6 weeks postpartum ]
• Receipt of blood transfusion [ Time Frame: From date of randomization until 6 weeks postpartum ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Heparin Prophylaxis Dosing for Antepartum Hospitalizations (HEPDOSE)
• Official Title: Randomized Control Trial of Unfractionated Heparin Thromboprophylaxis Dosing for Antepartum Hospitalizations
• 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.
• 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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Pregnancy Related
• Antepartum DVT

Intervention

• Drug: Standard Dose of Unfractionated Heparin
  5,000 units subcutaneous unfractionated heparin every 12 hours
• 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

Study Arms

• Active Comparator: Standard Dosing
  Standard dose of unfractionated heparin
  Intervention: Drug: Standard Dose of Unfractionated Heparin
• Active Comparator: Gestational Age-Based Dosing
  Dose of unfractionated heparin based on trimester of pregnancy
  Intervention: Drug: Gestational Age-Based Dose of Unfractionated Heparin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 13, 2020): 46
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 1, 2022
• Actual Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04635839
• Other Study ID Numbers: 20-001799
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Thalia Wong, MD, University of California, Los Angeles
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, Los Angeles
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of California, Los Angeles
• Verification Date: April 2023