Cesarean Section Surgery, Postpartum Period, VTE (Venous Thromboembolism)
Conditions
Keywords
Rivaroxaban, Enoxaparin, LMWH, DOAC, Thromboprophylaxis, Thrombin Generation, Endogenous Thrombin Potential, Post-cesarean
Brief summary
Pregnancy and the postpartum period increase venous thromboembolism (VTE) risk. After cesarean section, low-molecular-weight heparin (LMWH; enoxaparin) is commonly used for short-term thromboprophylaxis, but it requires daily subcutaneous injections and can cause adverse effects. Direct oral anticoagulants (DOACs) such as rivaroxaban offer convenient once-daily oral dosing. In women who meet institutional criteria for short-term postpartum thromboprophylaxis until hospital discharge, we will compare the laboratory anticoagulant effect of rivaroxaban versus enoxaparin using thrombin generation parameters. This randomized, open-label trial will enroll women undergoing elective cesarean section who are indicated for in-hospital prophylaxis. Blood will be drawn on postoperative day 2 at trough (pre-dose) and peak (\ 3 hours post-dose) to measure thrombin generation, anti-Xa activity and drug levels, and participants will complete the Anti-Clot Treatment Scale (ACTS) satisfaction questionnaire. Safety follow-up will occur by telephone at 2 days post-discharge and at 6 weeks postpartum.
Detailed description
Randomized (1:1), open-label, parallel-group, single-center study at Wolfson Medical Center. Eligible participants (Hebrew-speaking, age 18-50, elective cesarean, and meeting local VTE prophylaxis criteria) are randomized to rivaroxaban 10 mg PO once daily or enoxaparin 40 mg SC once daily from the day of surgery until discharge (first dose ≥12 h after cesarean and ≥6 h after spinal anesthesia). On POD2 two blood draws are performed: trough pre-dose and peak \ 3 h after dosing. Tests: PT, aPTT, anti-Xa with appropriate calibrators, thrombin generation (endogenous thrombin potential \[ETP\], lag time, peak thrombin). ACTS (Anti-Clot Treatment Scale (ACTS) satisfaction questionnaire) is administered before discharge. Safety follow-up calls 2 days after discharge and 6 weeks postpartum for bleeding, VTE, allergic reactions or other AEs.
Interventions
DRUGRivaroxaban
10 mg PO once daily from ≥12 h post-C-section until discharge
DRUGEnoxaparin 40 mg
40 mg SC once daily from ≥12 h post-C-section until discharge
Sponsors
Wolfson Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Hebrew-speaking women * age 18-50 * Elective cesarean at Wolfson * Indicated for in-hospital thromboprophylaxis per local protocol (need ≥2 risk factors among: cesarean delivery; age \>35; BMI \>30; parity ≥3; labor duration ≥12 h; postpartum hemorrhage or blood transfusion; reduced mobility)
Exclusion criteria
* Known thrombophilia * Prior arterial/venous thrombosis * Creatinine clearance \<29 mL/min * Abnormal liver enzymes/bilirubin or liver disease * Coagulation disorders * Platelets \<75,000/mm³ * Interacting drugs affecting DOAC metabolism (e.g., strong CYP3A4/P-gp modulators; azoles; protease inhibitors; rifampicin; phenytoin; carbamazepine; phenobarbital; St. John's wort; dronedarone) * Active bleeding or contraindication to anticoagulation * Peptic disease/GI bleeding history * Hemoptysis risk/history * Preeclampsia * Active infection * Significant lower-limb varicosities * Need for prophylaxis beyond discharge (≥3 risk factors) * Maternal weight \<50 kg or \>100 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endogenous Thrombin Potential (ETP) | Postoperative day 2: immediately before the study drug dose (trough) and approximately 3 hours after the study drug dose (peak), during the index hospitalization | Between-group comparison of ETP to assess similarity of anticoagulant effect; lower ETP indicates greater anticoagulation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thrombin Generation - Lag Time (minutes) | Postoperative day 2: immediately before the study drug dose (trough) and approximately 3 hours after the study drug dose (peak), during the index hospitalization | Thrombin Generation - Lag Time (minutes) |
| Thrombin Generation - Peak Thrombin (nM) | Postoperative day 2: immediately before the study drug dose (trough) and approximately 3 hours after the study drug dose (peak), during the index hospitalization | Thrombin Generation - Peak Thrombin (nM) |
| Anti-Xa activity (IU/mL) - Enoxaparin arm | Postoperative day 2: immediately before the enoxaparin dose (trough) and approximately 3 hours after the enoxaparin dose (peak), during the index hospitalization | Anti-Xa activity (IU/mL) - Enoxaparin arm |
| Plasma Rivaroxaban Concentration (ng/mL) - Rivaroxaban arm | Postoperative day 2: immediately before the rivaroxaban dose (trough) and approximately 3 hours after the rivaroxaban dose (peak), during the index hospitalization | Plasma Rivaroxaban Concentration (ng/mL) - Rivaroxaban arm |
| Treatment Satisfaction (ACTS Questionnaire total and subscales) | Postoperative day 2, prior to hospital discharge | The Anti-Clot Treatment Scale (validated patient-reported measure; higher scores reflect greater satisfaction) |
| Adverse Events (bleeding and VTE) | From randomization through 6 weeks postpartum, including assessment during the index hospitalization, approximately 2 days after discharge, and at 6 weeks postpartum | Clinically evident bleeding, confirmed VTE events, allergic reactions, or other AEs possibly related to study drugs, collected during hospitalization and via phone at \~2 days post-discharge and 6 weeks. |
Countries
Israel
Contacts
CONTACTOr Marom, MD
CONTACTHagit Eisenberg, MD
PRINCIPAL_INVESTIGATORAmihai Rottenstreich, MD
Wolfson Medical Center
STUDY_DIRECTORIlia Kleiner, MD
Wolfson Medical Center
STUDY_DIRECTORNoa Gonen, MD
Wolfson Medical Center
STUDY_DIRECTORHagit Eisenberg, MD
Wolfson Medical Center
Outcome results
None listed