Clinical trial NCT06831474: Excretion of Rivaroxaban in Human Breast Milk
Official title: Excretion of Rivaroxaban in Human Breast Milk
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Postpartum
VTE Prophylaxis
VTE (Venous Thromboembolism)
Rivaroxaban
Breastfeeding
Breast Milk Collection
Keywords: Rivaroxaban
Relative infant dose
LACT
Rivaroxaban in breast milk
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2025-02-18
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective phase 1, two arm drug trial comparing the excretion of rivaroxaban in human breast milk between groups receiving prophylactic or therapeutic dosing during the postpartum period. Patients will be screened and enrolled for participation either antepartum or postpartum.

Once postpartum, patients will be re-screened for any exclusion criteria and to be sure all inclusion criteria is met. Prior to receiving rivaroxaban each patient will provide a baseline 1 mL breast milk sample. Patients will either receive 10 mg or 20 mg daily of rivaroxaban starting by the first postpartum day. The dose will be be ordered by their postpartum physician team through the inpatient pharmacy and dispensed by their inpatient nursing team, as per standard of care at the discretion of their physician. 1 mL of breast milk will be collected at 3, 6, 12, 15 and 24 hours following their first morning dose. The patient will continue the medication while in house and for each subsequent day o
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to investigate the distribution of rivaroxaban into human milk at both therapeutic and prophylactic doses, and over time with repeated dosing.

Detailed description: The aim of our study is to perform a phase 1, single arm clinical trial to investigate the distribution of rivaroxaban into human milk at both therapeutic and prophylactic maternal doses. Our goal is to enhance the limited, although positive, data regarding the safety of rivaroxaban in breastfeeding. Our novel contributions to the existing body of literature will be in our investigation of rivaroxaban at both prophylactic and therapeutic doses, in repeated doses over time, and in a larger sample of participants. These results will provide physicians and national societies with safety data needed to properly counsel patients and advance clinical guidelines for postpartum care.

Eligibility criteria: Inclusion Criteria:

1. Postpartum within 6 weeks of delivery
2. Greater than 18 years old at expected date of delivery
3. English speaking
4. Hemodynamically stable without concern for ongoing blood loss
5. Non-breastfeeding
6. Or breastfeeding an infant born at or equal to 37 weeks' gestation, weighing \>2600g at birth and is not requiring intensive care
7. Meet inclusion criteria for prophylactic rivaroxaban dose: pre-pregnancy BMI \>/= 40 and/or any personal history of VTE. Or \>/= 2 of the following: pre-pregnancy BMI 30-39, immobility, pregnancy complications, cesarean delivery, hysterectomy
8. Or meet inclusion criteria for therapeutic rivaroxaban dose: have an indication for therapeutic anticoagulation per the American College of Obstetricians and Gynecologists' (ACOG) practice bulletin #196, or other indication per their primary team, and recommended for such anticoagulation per their primary practitioner.

Exclusion Criteria:

1. Pregnant
2. Less than 18 years old at estimated date of delivery
3. Hemodynamic instability and/or concern for ongoing blood loss
4. Newly diagnosed deep vein thrombosis (DVT) or pulmonary embolism (PE) in the postpartum period
5. Abnormal maternal renal or liver function (creatinine clearance \< 30 mL/min and/or liver function tests greater than lab normal)
6. A contraindication to rivaroxaban: hypersensitivity to rivaroxaban; active pathological bleeding
7. Breastfeeding an infant admitted to neonatal intensive care unit, infant gestational age at birth \<37w0d or weighing \<2600g.
8. If all of the following are met: age less than 40, ambulating, body mass index (BMI) less than 30, no active history of malignancy.
9. If patient lacks indication for therapeutic anticoagulation in the postpartum period per the American College of Obstetricians and Gynecologists' (ACOG) practice bulletin #196

Primary outcomes:
measure: Concentration of rivaroxaban in breast milk
timeFrame: Postpartum day 1
measure: Concentration of rivaroxaban in breast milk
timeFrame: Postpartum week 6
measure: Absolute infant dose of rivaroxaban
timeFrame: 6 week postpartum
measure: Relative infant dose
timeFrame: 6 weeks postpartum
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaria A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kallay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. doi: 10.1016/S2352-3026(19)30219-4. Epub 2019 Nov 5.
citation: Muysson M, Marshall K, Datta P, Rewers-Felkins K, Baker T, Hale TW. Rivaroxaban Treatment in Two Breastfeeding Mothers: A Case Series. Breastfeed Med. 2020 Jan;15(1):41-43. doi: 10.1089/bfm.2019.0124. Epub 2019 Sep 18.
citation: Saito J, Kaneko K, Yakuwa N, Kawasaki H, Yamatani A, Murashima A. Rivaroxaban Concentration in Breast Milk During Breastfeeding: A Case Study. Breastfeed Med. 2019 Dec;14(10):748-751. doi: 10.1089/bfm.2019.0230. Epub 2019 Nov 20.
citation: Wiesen MH, Blaich C, Muller C, Streichert T, Pfister R, Michels G. The Direct Factor Xa Inhibitor Rivaroxaban Passes Into Human Breast Milk. Chest. 2016 Jul;150(1):e1-4. doi: 10.1016/j.chest.2016.01.021.
citation: Zhao Y, Arya R, Couchman L, Patel JP. Are apixaban and rivaroxaban distributed into human breast milk to clinically relevant concentrations? Blood. 2020 Oct 8;136(15):1783-1785. doi: 10.1182/blood.2020006231. No abstract available.
citation: Bennett PN, ed. Drugs and human lactation, 2nd ed. Amsterdam. Elsevier. 1996.
citation: Lanitis T, Leipold R, Hamilton M, Rublee D, Quon P, Browne C, Cohen AT. Cost-effectiveness of Apixaban Versus Other Oral Anticoagulants for the Initial Treatment of Venous Thromboembolism and Prevention of Recurrence. Clin Ther. 2016 Mar;38(3):478-93.e1-16. doi: 10.1016/j.clinthera.2016.01.020. Epub 2016 Feb 26.
citation: Guillonneau M, de Crepy A, Aufrant C, Hurtaud-Roux MF, Jacqz-Aigrain E. [Breast-feeding is possible in case of maternal treatment with enoxaparin]. Arch Pediatr. 1996 May;3(5):513-4. doi: 10.1016/0929-693x(96)86421-9. No abstract available. French.
citation: American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Obstet Gynecol. 2018 Jul;132(1):e1-e17. doi: 10.1097/AOG.0000000000002706.