Antepartum DVT, Pregnancy Related
Conditions
Keywords
Thromboprophylaxis, Antepartum admission, Heparin
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.
Interventions
5,000 units subcutaneous unfractionated heparin every 12 hours
DRUGGestational 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
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Elevated Serum Activated Partial Thromboplastin Time Above the Normal Range (> 36.2 Seconds). | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Mode of Delivery | Assessed at time of delivery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Dosing Standard dose of unfractionated heparin
Standard Dose of Unfractionated Heparin: 5,000 units subcutaneous unfractionated heparin every 12 hours | 21 |
| Gestational Age-Based Dosing Dose of unfractionated heparin based on trimester of pregnancy
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 | 24 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Delivered prior to second dose of heparin | 1 | 0 |
Baseline characteristics
| Characteristic | Standard Dosing | Gestational Age-Based Dosing | Total |
|---|---|---|---|
| Age, Continuous | 32 years | 34 years | 33 years |
| Body mass index | 29.9 kg/m^2 | 30.4 kg/m^2 | 30.1 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 12 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Gestational age at randomization | 30.3 weeks | 30.4 weeks | 30.3 weeks |
| Gravida | 2 pregnancies | 2 pregnancies | 2 pregnancies |
| Nulliparous | 15 Participants | 10 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 16 Participants |
| Region of Enrollment United States | 21 participants | 24 participants | 45 participants |
| Sex: Female, Male Female | 21 Participants | 24 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 24 |
| other Total, other adverse events | 0 / 21 | 0 / 24 |
| serious Total, serious adverse events | 0 / 21 | 0 / 24 |
Outcome results
Primary
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
Time frame: Collected 6 hours after unfractionated heparin dose until patient was taken of unfractionated heparin, an average of 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants With Elevated Serum Activated Partial Thromboplastin Time Above the Normal Range (> 36.2 Seconds). | 1 Participants |
| Gestational Age-Based Dosing | Number of Participants With Elevated Serum Activated Partial Thromboplastin Time Above the Normal Range (> 36.2 Seconds). | 8 Participants |
Secondary
Estimated Blood Loss From Delivery
Time frame: Assessed at time of delivery
Population: 1 participant in Arm 1 (standard dosing) delivered at an outside hospital and estimated blood loss is unavailable
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Dosing | Estimated Blood Loss From Delivery | 654 cc |
| Gestational Age-Based Dosing | Estimated Blood Loss From Delivery | 593 cc |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Dosing | Maximum Activated Partial Thromboplastin Clotting Time Levels Measured | 26.6 seconds |
| Gestational Age-Based Dosing | Maximum Activated Partial Thromboplastin Clotting Time Levels Measured | 30.4 seconds |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Dosing | Maximum Anti-Factor Xa Level Measured | 0.09 IU/mL |
| Gestational Age-Based Dosing | Maximum Anti-Factor Xa Level Measured | 0.09 IU/mL |
Secondary
Mode of Delivery
Time frame: Assessed at time of delivery
Population: 1 participant in Arm 1 (standard dosing) delivered at an outside hospital and mode of delivery is unavailable
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Dosing | Mode of Delivery | Vaginal delivery | 6 Participants |
| Standard Dosing | Mode of Delivery | Cesarean delivery | 14 Participants |
| Gestational Age-Based Dosing | Mode of Delivery | Vaginal delivery | 4 Participants |
| Gestational Age-Based Dosing | Mode of Delivery | Cesarean delivery | 20 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants Diagnosed With Venous Thromboembolism (Pulmonary Embolism and/or Deep Venous Thromboembolism) | 1 Participants |
| Gestational Age-Based Dosing | Number of Participants Diagnosed With Venous Thromboembolism (Pulmonary Embolism and/or Deep Venous Thromboembolism) | 0 Participants |
Secondary
Number of Participants That Had a Delay in Timing of Delivery Due to Unfractionated Heparin
Time frame: Assessed at time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants That Had a Delay in Timing of Delivery Due to Unfractionated Heparin | 0 Participants |
| Gestational Age-Based Dosing | Number of Participants That Had a Delay in Timing of Delivery Due to Unfractionated Heparin | 0 Participants |
Secondary
Number of Participants That Received a Blood Transfusion
Time frame: From time of delivery until 6 weeks after delivery
Population: 1 participant in Arm 1 (standard dosing) delivered at an outside hospital and need for blood transfusion is unavailable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants That Received a Blood Transfusion | 1 Participants |
| Gestational Age-Based Dosing | Number of Participants That Received a Blood Transfusion | 7 Participants |
Secondary
Number of Participants That Received General Anesthesia
Time frame: Assessed at time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants That Received General Anesthesia | 1 Participants |
| Gestational Age-Based Dosing | Number of Participants That Received General Anesthesia | 0 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Dosing | Number of Participants Who Did Not Receive or Had a Delay of Neuraxial Anesthesia Due to Unfractionated Heparin | 0 Participants |
| Gestational Age-Based Dosing | Number of Participants Who Did Not Receive or Had a Delay of Neuraxial Anesthesia Due to Unfractionated Heparin | 0 Participants |