Dose Optimization of Rivaroxaban Combined With Rifampicin

NCT05658042 | Unknown

• 1 other identifier: 2022-LCYJ-PY-41
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn about exposure levels of rivaroxaban at different doses in patients with prosthetic joint infection combined with the use of rifampicin. Participants will be collected blood samples to determine rivaroxaban plasma concentration. The main question it aims to answer is to predict the dose adjustment of rivaroxaban combined with the use of rifampin.

Conditions

Infections

Keywords

periprosthetic infection; rivaroxaban

Outcome Measures

Primary Outcomes (1)

• plasma concentration of rivaroxaban

  HPLC-MS/MS method

  2-4 hours and 12-16 hours after 2-5 days of continuous dosing for rivaroxaban

Secondary Outcomes (2)

• incidence of adverse reactions

  From admission to discharge, up to 3 week

• effect indicator

  From admission to discharge, up to 3 week

Study Arms (4)

rivaroxaban 10mg qd

nonintervention

rivaroxaban 10mg qd+rifampicin

nonintervention

rivaroxaban 20mg qd+rifampicin

nonintervention

rivaroxaban 15mg bid+rifampicin

nonintervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

hospitalized patients

You may qualify if:

• Patients aged\>18 years
• The diagnosis was periprosthetic infection after joint replacement
• Orthopedic operations such as revision of artificial joints, removal of prostheses, debridement, etc. for the treatment of periprosthetic infection
• Rivaroxaban was used to prevent deep vein thrombosis after operation.

You may not qualify if:

• Patients allergic to any excipient in rivaroxaban, rifampicin or tablets
• Patients with clinically significant active bleeding
• Patients with significant risk of bleeding
• Patients with liver disease with coagulation abnormalities and clinical-related bleeding risk, including patients with cirrhosis who reached Child Pugh C grade
• Pregnant women and breastfeeding women
• Patients taking combined drugs affecting rivaroxaban metabolism
• Patients who were unable or unwilling to cooperate with the study (Such as mental or memory disorders)
• Patients discontinued without meeting study target days
• Patients with severe renal insufficiency (creatinine clearance rate \< 30ml / min)

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

RECRUITING

Related Publications (12)

• Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW Jr. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e278S-e325S. doi: 10.1378/chest.11-2404.

  PMID: 22315265 BACKGROUND

• Gnoth MJ, Buetehorn U, Muenster U, Schwarz T, Sandmann S. In vitro and in vivo P-glycoprotein transport characteristics of rivaroxaban. J Pharmacol Exp Ther. 2011 Jul;338(1):372-80. doi: 10.1124/jpet.111.180240. Epub 2011 Apr 22.

  PMID: 21515813 BACKGROUND

• Lang D, Freudenberger C, Weinz C. In vitro metabolism of rivaroxaban, an oral, direct factor Xa inhibitor, in liver microsomes and hepatocytes of rats, dogs, and humans. Drug Metab Dispos. 2009 May;37(5):1046-55. doi: 10.1124/dmd.108.025551. Epub 2009 Feb 5.

  PMID: 19196846 BACKGROUND

• Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009 May;37(5):1056-64. doi: 10.1124/dmd.108.025569. Epub 2009 Feb 5.

  PMID: 19196845 BACKGROUND

• Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, Rao N, Hanssen A, Wilson WR; Infectious Diseases Society of America. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013 Jan;56(1):e1-e25. doi: 10.1093/cid/cis803. Epub 2012 Dec 6.

  PMID: 23223583 BACKGROUND

• Vakkalagadda B, Frost C, Byon W, Boyd RA, Wang J, Zhang D, Yu Z, Dias C, Shenker A, LaCreta F. Effect of Rifampin on the Pharmacokinetics of Apixaban, an Oral Direct Inhibitor of Factor Xa. Am J Cardiovasc Drugs. 2016 Apr;16(2):119-27. doi: 10.1007/s40256-015-0157-9.

  PMID: 26749408 BACKGROUND

• Altena R, van Roon E, Folkeringa R, de Wit H, Hoogendoorn M. Clinical challenges related to novel oral anticoagulants: drug-drug interactions and monitoring. Haematologica. 2014 Feb;99(2):e26-7. doi: 10.3324/haematol.2013.097287. No abstract available.

  PMID: 24497568 BACKGROUND

• Becerra AF, Amuchastegui T, Tabares AH. Decreased Rivaroxaban Levels in a Patient with Cerebral Vein Thrombosis Receiving Phenytoin. Case Rep Hematol. 2017;2017:4760612. doi: 10.1155/2017/4760612. Epub 2017 Aug 10.

  PMID: 28875044 BACKGROUND

• Mueck W, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Kalebo P, Muelhofer E, Misselwitz F, Eriksson BI. Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost. 2008 Sep;100(3):453-61.

  PMID: 18766262 BACKGROUND

• Wyse DG. Targeted Therapeutic Drug Monitoring for Direct Oral Anticoagulants: What Is Its Potential Place and Can It Limit Black Swan Events? Can J Cardiol. 2018 Nov;34(11):1393-1395. doi: 10.1016/j.cjca.2018.08.006. Epub 2018 Aug 9. No abstract available.

  PMID: 30404744 BACKGROUND

• Bernier M, Lancrerot SL, Parassol N, Lavrut T, Viotti J, Rocher F, Drici MD. Therapeutic Drug Monitoring of Direct Oral Anticoagulants May Increase Their Benefit-Risk Ratio. J Cardiovasc Pharmacol. 2020 Oct;76(4):472-477. doi: 10.1097/FJC.0000000000000870.

  PMID: 33030858 BACKGROUND

• Min JS, Bae SK. Prediction of drug-drug interaction potential using physiologically based pharmacokinetic modeling. Arch Pharm Res. 2017 Dec;40(12):1356-1379. doi: 10.1007/s12272-017-0976-0. Epub 2017 Oct 27.

  PMID: 29079968 BACKGROUND

MeSH Terms

Conditions

Infections

Study Officials

• Ruijuan Xu

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  STUDY DIRECTOR

Central Study Contacts

Ruijuan Xu

CONTACT

+8613851502360; jean0129@163.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2022
• First Posted: December 20, 2022
• Study Start: July 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: December 20, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)