Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin

Endocarditis Clinical Trial

Official title: Pharmacokinetics/ Pharmacodynamics (PK/PD) Study of Vancomycin in the Treatment of Methicillin-resistant Staphylococcus Aureus（MRSA） Blood Stream Infection (Septicemia) and Endocarditis in Chinese Patients

Status Recruiting

Clinical Trial Summary

1. Drug resistance of G+ cocci is a severe healthcare problem. According to the Ministry of Health National Antimicrobial Resistant Investigation Net (mohnarin) surveillance report, the isolation rate of MRSA is some 60% in China. MRSA infection has become a serious clinical problem;

2. Vancomycin is a bactericidal glycopeptide antibiotic which inhibits bacterial growth by hindering the synthesis of cell wall in bacteria. It exerts strong antibiotic effect to Gram+ bacteria. It is indicated for serious staphylococcus infections especially MRSA infection and has become the gold standard agent in MRSA treatment;

3. Vancomycin is a time-dependent antibiotic, its clinical and microbiological efficacy is related to area under curve（ AUC）/minimum inhibitory concentration （MIC ）(AUIC). Cmin at steady state is an surrogate parameter of AUIC, which is closely associated to the efficacy;

4. AUIC >400 and Cmin between 15~20 mg/L are recommended for effective vancomycin treatment by Infectious Diseases Society of America （IDSA） although it is still disputable;

5. Due to the absence of PK/PD study on vancomycin in China, administration of vancomycin is performed in reference to the recommendation of IDSA. Its suitability to Chinese patients is still to be clarified;

6. Plasma concentrations of vancomycin vary significantly between population and individuals. Factors such as large-volume fluid infusion, hypoproteinemia and renal clearance, etc. will influence the distribution and excretion of vancomycin, resulting in different plasma concentrations between individuals. Results of PK studies differ greatly between China and abroad. Administration based on the AUIC or Cmin recommended by IDSA would not be suitable to Chinese patients. Given the definite long-term benefit of vancomycin treatment, the AUIC or Cmin suitable to Chinese patients must be identified by clinical study.

7. The PK/PD study on vancomycin in the treatment to MRSA septicemia and endocarditis is of great significance for more reasonable use and improved therapeutic efficacy of MRSA infection.

Clinical Trial Description

Study design:

A multi-center, non-controlled, open-labeled observational study

Research objectives

Primary objective:

To explore the PK/PD target value (AUIC) of vancomycin in the treatment of MRSA septicemia and endocarditis in Chinese patients.

Secondary objective:

To detect the therapeutic efficacy and safety of vancomycin in the treatment of MRSA septicemia and endocarditis in Chinese patients.

To exam the relationship between the Cmin of vancomycin and its efficacy in the treatment to MRSA septicemia and endocarditis.

To explore the relationship between MRSA molecular type and vancomycin therapeutic efficacy

Medicine and administration

Drug:

Vancomycin

Dosing:

15~20 mg/kg, IV, q 12~8h (or 1 g, IV, q12~8h) for adult patient with normal renal function; Dosage should be adjusted by blood creatinine clearance in patients with impaired renal function; Administration route： 1~2 h/ dosing, IV

Drug combination:

Drug combination is not recommended for patients with simple MRSA infection; Rifampicin can be combined in case of MRSA artificial valve endocarditis; Anti-G- antibacterial agents can be combined in case of concurrent G- bacterial infections.

Duration:

Septicemia: 2~4 weeks Endocarditis: 6~8 weeks ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Stream Infections
• Endocarditis
• Infection
• MRSA

• NCT number: NCT02443064
• Study type: Interventional
• Source: Zhejiang University
• Contact: Yong-hong Xiao, MD
• Phone: +86-571-87236421
• Email: xiao-yonghong@163.com
• Status: Recruiting
• Phase: Phase 4
• Start date: January 2014
• Completion date: June 2016