Excretion of Rivaroxaban in Human Breast Milk (LACT)

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.

Study Overview

• Status: Recruiting
• Conditions: Breastfeeding; Postpartum; Breast Milk Collection; Rivaroxaban; VTE Prophylaxis; VTE (Venous Thromboembolism)
• Intervention / Treatment: Drug: Rivaroxaban 10 MG Oral Tablet; Drug: Rivaroxaban 20 MG Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sophie H Green, MD; Phone Number: 215-955-5500; Email: sophie.green@jefferson.edu
• Study Contact Backup: Name: Rupsa C Boelig, MD; Phone Number: 215-955-5500; Email: rupsa.boelig@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Sophie Green, MD; Phone Number: 215-955-5000; Email: sophie.green@jefferson.edu
      • Principal Investigator: Rupsa C Boelig, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prophylactic rivaroxaban; Patients will receive 10 mg daily of rivaroxaban starting by the first postpartum day. The medication will be ordered by their postpartum physician team through the inpatient pharmacy and dispensed by their inpatient nursing team, as per standard of care. The decision for dose 10 mg vs 20 mg of rivaroxaban is based on inclusion criteria and patient's physician team's recommendation for prophylactic (10 mg) vs. therapeutic (20 mg) dosing.	Drug: Rivaroxaban 10 MG Oral Tablet; 10mg rivaroxaban daily; Other Names: Xarelto
Active Comparator: Therapeutic or Intermediate dose rivaroxaban; Patients will receive 20 mg daily of rivaroxaban starting by the first postpartum day. The medication will be ordered by their postpartum physician team through the inpatient pharmacy and dispensed by their inpatient nursing team, as per standard of care. The decision for 10 mg vs 20 mg of rivaroxaban is based on inclusion criteria and patient's physician team's recommendation for prophylactic (10 mg) vs. therapeutic (20 mg) dosing.	Drug: Rivaroxaban 20 MG Oral Tablet; 20mg rivaroxaban daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of rivaroxaban in breast milk	Time/Concentration profile of rivaroxaban in breast milk prior to intake (0) and 3, 6, 12, 15 and 24 hours following morning dose on day 0-1	Postpartum day 1
Concentration of rivaroxaban in breast milk	Time/concentration profile of rivaroxaban in breast milk 3 hours following morning dose on day 2 and onward	Postpartum week 6
Absolute infant dose of rivaroxaban	The absolute infant dose is calculated from average drug concentrations in breast milk multiplied by an estimated breast milk intake of 150 mL/kg/day.	6 week postpartum
Relative infant dose	The relative infant dose is the absolute infant dose expressed as a percentage of the weight adjusted maternal dose, based on an average maternal weight of 75 kg. It is expressed in mg/kg/day.	6 weeks postpartum

Collaborators and Investigators

• Sponsor: Thomas Jefferson University

Publications and helpful links

General 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, 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Pregnancy Mortality Surveillance System

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Rivaroxaban; Relative infant dose; LACT; Rivaroxaban in breast milk
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban
• Other Study ID Numbers: iRISID-2025-0397

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The participant data will be kept confidential and access will be limited to the study investigators in order to respect the privacy of the participants.

Drug and device information, study documents

• 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.: Yes