Dose Optimization of Rivaroxaban Combined With Rifampicin

Infections Clinical Trial

Official title:

Therapeutic Drug Monitoring Combined With Quantitative Pharmacology for Dose Optimization of Rivaroxaban in Combination With Rifampicin in Patients With Periprosthetic Joint Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05658042
• Other study ID #: 2022-LCYJ-PY-41
• Status: Recruiting
• Start date: July 1, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Ruijuan Xu
• Phone: +8613851502360
• Email: jean0129[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

This study is a prospective observational study and does not interfere with the normal clinical diagnosis and treatment process. In the case of patients with periprosthetic infection with or without rifampicin, the blood concentration of rivaroxaban was monitored, and the data were further predicted and analyzed by statistical tests and physiological pharmacokinetic models, and suggestions were made for dose optimization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Infections

Locations

Country	Name	City	State
China	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	incidence of adverse reactions	Bleeding and anemia	From admission to discharge, up to 3 week
Secondary	effect indicator	Activated Partial Thromboplastin Time and Prothrombin time	From admission to discharge, up to 3 week