Excretion of Rivaroxaban in Human Breast Milk

Overview

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.

Interventions

• Drug Rivaroxaban 10 MG Oral Tablet
  10mg rivaroxaban daily
• Drug Rivaroxaban 20 MG Oral Tablet
  20mg rivaroxaban daily

Primary outcome measures

• Concentration of rivaroxaban in breast milk [Time frame: Postpartum day 1]
• Concentration of rivaroxaban in breast milk [Time frame: Postpartum week 6]
• Absolute infant dose of rivaroxaban [Time frame: 6 week postpartum]
• Relative infant dose [Time frame: 6 weeks postpartum]

Eligibility criteria

Inclusion criteria

• Postpartum within 6 weeks of delivery
• Greater than 18 years old at expected date of delivery
• English speaking
• Hemodynamically stable without concern for ongoing blood loss
• Non-breastfeeding
• Or breastfeeding an infant born at or equal to 37 weeks' gestation, weighing >2600g at birth and is not requiring intensive care
• 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
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Thomas Jefferson University Hospital — Philadelphia

Publications

• 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, Cro PMID 31699660
• 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. PMID 31532233
• 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. PMID 31746638
• 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. PMID 27396794
• 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. PMID 32488251
• Bennett PN, ed. Drugs and human lactation, 2nd ed. Amsterdam. Elsevier. 1996.
• 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. PMID 26922297
• 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. PMID 8763733

Identifiers

NCT: NCT06831474 · iRISID-2025-0397

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗