Vancomycin Versus Daptomycin for the Treatment of Methicillin Resistant Staphylococcus Aureus (MRSA) Bacteremia

NCT01975662 | Terminated Phase 2 DMC

• 1 other identifier: SIDI-MRSA-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to compare the efficacy of daptomycin treatment versus vancomycin treatment in the treatment of methicillin resistant staphylococcus aureus (MRSA) bloodstream infections (BSI) due to isolates with high vancomycin minimum inhibitory concentrations (MIC) (i.e. \> or equal to 1.5 ug/ml) in terms of reducing all-cause mortality. Our secondary aim is to compare clinical failure rates of daptomycin treatment versus vancomycin treatment and to compare time to microbiological clearance in patients treated with daptomycin versus those treated with vancomycin. Our primary hypothesis is that Daptomycin treatment is superior to vancomycin treatment in reducing mortality from BSIs due to MRSA with high vancomycin MIC from 25% to 10%.

Conditions

Bacteremia Due to Staphylococcus Aureus

Keywords

MRSA; bacteremia; vancomycin; daptomycin

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  To compare the efficacy of daptomycin treatment versus vancomycin treatment in the treatment of MRSA BSIs due to isolates with high vancomycin MICs (i.e. \> or equal to 1.5 ug/L) in terms of reducing all-cause mortality 60 days from the time of index blood culture.

  60 days

Secondary Outcomes (9)

• Rates of clinical failure

  60 days

• Time to microbiological clearance

  60 days

• Rates of nephrotoxicity

  60 days

• Rates of musculoskeletal toxicity

  60 days

• The need to stop the study drug due to toxicity

  60 days

Other Outcomes (2)

• All cause mortality in the different subtypes of bacteremia

  60 days

• Rates of clinical failure in the different subtypes of bacteremia

  60 days

Study Arms (2)

Daptomycin

EXPERIMENTAL

Daptomycin will be dosed intravenously at 6-8mg/kg every 24 hours. Patients with uncomplicated bacteremia will receive a dose of 6mg/kg every 24 hours. Patients with suspected complicated bacteremia or endocarditis, or receipt of at least two doses of vancomycin in the last 90 days (apart from vancomycin received for their current MRSA bacteremia) will receive a dose of 8mg/kg every 24 hours. In patients with a creatinine clearance less than 30ml/min, or on intermittent or continuous hemodialysis, daptomycin will be dosed at 6-8mg/kg every 48 hours. The same criteria as above applies as to whether they receive 6mg/kg or 8mg/kg every 48hours. Daptomycin will be administered after hemodialysis in patients undergoing intermittent hemodialysis.

Drug: Daptomycin

Vancomycin

ACTIVE COMPARATOR

Vancomycin will be dosed at 15mg/kg every 12 hours with appropriate dose adjustments by a pharmacist in patients with a creatinine clearance less than 50 ml/min, so as to achieve a vancomycin trough level of 15-20ug/ml.

Drug: Vancomycin

Interventions

Daptomycin DRUG

Duration of treatment will be determined based on the type of bacteremia. Patients with uncomplicated bacteremia will receive a minimum of 14 days antibiotics and those with complicated bacteremia or infective endocarditis will receive a minimum of 28 to 42 days antibiotics from the date that microbiological clearance is achieved.

Also known as: Cubicin

Daptomycin

Vancomycin DRUG

Duration of treatment will be determined based on the type of bacteremia. Patients with uncomplicated bacteremia will receive a minimum of 14 days antibiotics and those with complicated bacteremia or infective endocarditis will receive a minimum of 28 to 42 days antibiotics from the date that microbiological clearance is achieved.

Also known as: Vancomycin Hydrochloride

Vancomycin

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 21 years.
• Inpatient at the time of enrolment.
• MRSA bacteremia due to MRSA isolates with a vancomycin MIC \> 1.5 ug/ml.
• Be prepared to undergo all treatments and procedures, and attend follow-ups as per the trial protocol.

You may not qualify if:

• Allergy to any of the study medications.
• Pregnant or breastfeeding females.
• Unable to provide consent or have no legally authorized representatives.
• Currently enrolled or within the past three months participated in an interventional antibiotic or vaccine trial.
• \>48 hours after MRSA vancomycin MIC \> or equal to1.5 ug/ml confirmation by the microbiology laboratory (assessed from time of lab report).
• Patients on palliative care or with less than 24 hours of life expectancy (as discussed with their primary physicians).
• Polymicrobial bacteremia \[see (a) below\].
• Pneumonia \[see (b) below\].
• On treatment with linezolid, tigecycline or ceftaroline immediately prior to enrolment.
• Previous blood cultures positive for MRSA in the preceding one month.
• On vancomycin or daptomycin treatment for more than 96 hours prior to enrolment.
• BSI due to MRSA with vancomycin MIC \> or equal to 4 ug/ml.
• Baseline serum creatine kinase more than 1.5 times the upper limit of normal.
• Patients with prosthetic heart valves
• Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.

Sponsors & Collaborators

• Singapore General Hospital: lead
• Singapore Clinical Research Institute: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Related Publications (2)

• Kalimuddin S, Chan YFZ, Phillips R, Ong SP, Archuleta S, Lye DC, Tan TT, Low JGH. A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations - results of a prematurely terminated study. Trials. 2018 Jun 1;19(1):305. doi: 10.1186/s13063-018-2702-8.

  PMID: 29859132 DERIVED

• Kalimuddin S, Phillips R, Gandhi M, de Souza NN, Low JG, Archuleta S, Lye D, Tan TT. Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial. Trials. 2014 Jun 19;15:233. doi: 10.1186/1745-6215-15-233.

  PMID: 24943129 DERIVED

MeSH Terms

Conditions

Bacteremia

Interventions

Daptomycin; Vancomycin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Glycopeptides; Glycoconjugates; Carbohydrates

Study Officials

• Thuan Tong Tan, MBBS, PhD

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2013
• First Posted: November 5, 2013
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 14, 2016

Record last verified: 2016-04

Locations

SG (1)