Excretion of Rivaroxaban in Human Breast Milk

NCT06831474 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: iRISID-2025-0397
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Postpartum; VTE Prophylaxis; VTE (Venous Thromboembolism); Rivaroxaban; Breastfeeding; Breast Milk Collection

Keywords

Rivaroxaban; Relative infant dose; LACT; Rivaroxaban in breast milk

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

Prophylactic rivaroxaban

ACTIVE COMPARATOR

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

Therapeutic or Intermediate dose rivaroxaban

ACTIVE COMPARATOR

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

Interventions

Rivaroxaban 10 MG Oral Tablet DRUG

10mg rivaroxaban daily

Also known as: Xarelto

Prophylactic rivaroxaban

Rivaroxaban 20 MG Oral Tablet DRUG

20mg rivaroxaban daily

Therapeutic or Intermediate dose rivaroxaban

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Related Publications (9)

• 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.

  PMID: 31699660 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Bennett PN, ed. Drugs and human lactation, 2nd ed. Amsterdam. Elsevier. 1996.

  BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 29939938 BACKGROUND

MeSH Terms

Conditions

Venous Thromboembolism; Breast Feeding; Breast Milk Expression

Interventions

Rivaroxaban; Tablets

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Sophie H Green, MD

CONTACT

215-955-5500; sophie.green@jefferson.edu

Rupsa C Boelig, MD

CONTACT

215-955-5500; rupsa.boelig@jefferson.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: February 18, 2025
• Study Start: July 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)