NCT02443064

Brief Summary

  1. 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. 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. 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. 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. 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. 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Jan 2014

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2014

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

November 23, 2014

Completed
6 months until next milestone

First Posted

Study publicly available on registry

May 13, 2015

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

May 13, 2015

Status Verified

May 1, 2015

Enrollment Period

2 years

First QC Date

November 23, 2014

Last Update Submit

May 8, 2015

Conditions

Blood Stream InfectionsEndocarditisMRSA

Keywords

Pharmacokinetics/pharmacodynamicsvancomycinblood stream infectionsChinese patientsMRSA

Outcome Measures

Primary Outcomes (1)

  • AUC/MIC of vancomycin in each patient

    Participants will be followed for the duration of hospital stay, an expected average of 4 weeks

Secondary Outcomes (3)

  • Number of participants with negative blood culture at the end of treatment

    Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment

  • Number of participants with adverse events

    Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment

  • Number of participants survival

    Participants will be followed during vancomycin treatment and in average of 4 weeks after vancomycin treatment

Study Arms (1)

MRSA blood stream infection patient

EXPERIMENTAL

Intervention:Vancomycin Dosing: 15-20mg/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

Drug: Vancomycin

Interventions

VancomycinDRUG

Vancomycin was administered for Chinese patients with MRSA blood stream infection and endocarditis Pharmacokinetics: 5 blood samples collected at steady state for the determination of plasma concentrations for population pharmacokinetics (PPK) analysis. Microbiology: blood cultures for MRSA isolation, MIC of vancomycin against MRSA; molecular typing will be analyzed on bacterial strains including heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and vancomycin-intermediate Staphylococcus aureus （VISA); Safety evaluation: hepatic and renal function, blood routine test, and so on.

MRSA blood stream infection patient

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years, male or female;
  • diagnosed as MRSA septicemia or endocarditis; Septicemia clinical manifestations of infection; MRSA infection confirmed by blood culture; Endocarditis: diagnosed according to modified Duke Criteria
  • no therapy with effective anti-MRSA drugs 72 hours prior to the study; Effective anti-MRSA drugs used in China include: vancomycin, norvancomycin, teicoplanin, linezolid, daptomycin, tigecycline, and fusidic acid.

You may not qualify if:

  • those being allergic to glycopeptides antibiotics;
  • those with osteomyelitis, central nervous system infection or other septic migrations (except for endocarditis);
  • patients with catheter-related bloodstream infection who cannot withdraw catheter;
  • those during chemotherapy for cancer or leukemia;
  • those with agranulocytosis;
  • those with HIV infection;
  • women in pregnancy or lactation;
  • patients receiving vancomycin for less than 72 hours;
  • patients participating in any other clinical trial in 3 months prior to the study (not limited to trials for antibiotics)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Yong-Hong Xiao

Hangzhou, Zhejiang, 310003, China

RECRUITING

Related Publications (6)

  • Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis. 2011 Apr 15;52(8):975-81. doi: 10.1093/cid/cir124.

    PMID: 21460309BACKGROUND

  • Brown J, Brown K, Forrest A. Vancomycin AUC24/MIC ratio in patients with complicated bacteremia and infective endocarditis due to methicillin-resistant Staphylococcus aureus and its association with attributable mortality during hospitalization. Antimicrob Agents Chemother. 2012 Feb;56(2):634-8. doi: 10.1128/AAC.05609-11. Epub 2011 Nov 28.

    PMID: 22123681BACKGROUND

  • Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4.

    PMID: 21208910BACKGROUND

  • Anonymous. Expert consensus on the use of vancomycin(2011). Chin J of New Drug & Regimen. 2011，30（8）：561-56

    BACKGROUND

  • 1.Xiao YH, et al. 2010 report of Mohnarin. Chin J Nosocomial Infect. 2012, 22(22):4946-4952

    RESULT

  • Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925-42. doi: 10.2165/00003088-200443130-00005.

    PMID: 15509186RESULT

MeSH Terms

Conditions

Endocarditis

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

GlycopeptidesGlycoconjugatesCarbohydratesPeptidesAmino Acids, Peptides, and Proteins

Study Officials

  • Yong-hong Xiao, MD

    The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong-hong Xiao, MD

CONTACT

+86-571-87236421xiao-yonghong@163.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Vice Director, China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou.

Study Record Dates

First Submitted

November 23, 2014

First Posted

May 13, 2015

Study Start

January 1, 2014

Primary Completion

January 1, 2016

Study Completion

June 1, 2016

Last Updated

May 13, 2015

Record last verified: 2015-05

Locations

CN(1)