ClinicalTrials.gov

History of Changes for Study: NCT01975662
Comparison of Vancomycin Versus Daptomycin for the Treatment of Methicillin Resistant Staphylococcus Aureus Bacteremia
Latest version (submitted April 12, 2016) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 October 29, 2013 None (earliest Version on record)
2 November 11, 2013 Study Description, Outcome Measures, Study Status and Study Identification
3 February 2, 2014 Recruitment Status, Study Status, Contacts/Locations, Eligibility and Oversight
4 April 12, 2016 Recruitment Status, Study Status, Contacts/Locations and Study Design
Comparison Format:

Scroll up to access the controls

Study NCT01975662
Submitted Date:  October 29, 2013 (v1)

Open or close this module Study Identification
Unique Protocol ID: SIDI-MRSA-001
Brief Title: Comparison of Vancomycin Versus Daptomycin for the Treatment of Methicillin Resistant Staphylococcus Aureus Bacteremia
Official Title: A Multi-centre Open Label Randomized Controlled Phase IIB Trial Comparing Vancomycin Versus Daptomycin for the Treatment of MRSA Bacteremia Due to Isolates With High Vancomycin Minimum Inhibitory Concentrations
Secondary IDs:
Open or close this module Study Status
Record Verification: October 2013
Overall Status: Not yet recruiting
Study Start: February 2014
Primary Completion: November 2015 [Anticipated]
Study Completion: December 2015 [Anticipated]
First Submitted: October 29, 2013
First Submitted that
Met QC Criteria:
October 29, 2013
First Posted: November 5, 2013 [Estimate]
Last Update Submitted that
Met QC Criteria:
October 29, 2013
Last Update Posted: November 5, 2013 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Singapore General Hospital
Responsible Party: Sponsor
Collaborators: Singapore Clinical Research Institute
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

The aim of this study is 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.

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%.

Detailed Description:

Introduction/Clinical Significance Vancomycin is the standard first-line treatment for methicillin resistant Staphylococcus aureus (MRSA) bacteremia. In recent years however, there has been an increase in the number of MRSA isolates with high vancomycin minimum inhibitory concentrations (MIC) [1]. Recent consensus guidelines recommend clinicians consider using alternative agents such as daptomycin for MRSA infection when the vancomycin MIC is greater than 1 ug/ml [2]. To date however, there has been no head to head randomized trial comparing the safety and efficacy of daptomycin and vancomycin in the treatment of blood stream infections (BSIs) due to MRSA with high vancomycin MICs.

Specific Aims:

Our primary aim is 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.

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.

Hypothesis:

Daptomycin treatment is superior to vancomycin treatment in reducing mortality from BSIs due to MRSA with high vancomycin MIC from 25% to 10%.

Methodology We will conduct a prospective open label randomized controlled phase 2B pilot study in 3 major Singaporean hospitals, with balanced treatment assignments within each hospital achieved by permuted block randomization. There will be 21 subjects per arm, with the control arm receiving vancomycin and the experimental arm receiving daptomycin. The primary objective is 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 positive index blood culture. Secondary outcomes include rates of clinical failure, time to microbiological clearance, and rates of nephro- and muscular toxicities in both arms.

If the pilot study proves our hypothesis that indeed , we aim to proceed with a larger scale trial

Open or close this module Conditions
Conditions: Bacteremia Due to Staphylococcus Aureus
Keywords: MRSA
bacteremia
vancomycin
daptomycin
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 50 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Daptomycin

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
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.
Other Names:
  • Cubicin
Active Comparator: Vancomycin
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
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.
Other Names:
  • Vancomycin Hydrochloride
Open or close this module Outcome Measures
Primary Outcome Measures:
1. All cause mortality
[ Time Frame: 60 days ]

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.
Secondary Outcome Measures:
1. Rates of clinical failure
[ Time Frame: 60 days ]

Our secondary aims are:

1.To compare the rates of 'clinical failure' as per the following definitions:

i.To compare clinical failure rates of daptomycin treatment versus vancomycin treatment defined as a composite of all-cause mortality 60 days from index blood culture, microbiologic failure and/or a recurrence of MRSA BSI.

ii.To compare clinical failure rates of daptomycin treatment versus vancomycin treatment defined as microbiologic failure and/or a recurrence of MRSA BSI.

iii.To compare clinical failure rates of daptomycin treatment versus vancomycin treatment defined as a composite of all-cause mortality 60 days from index blood culture and/or microbiologic failure.

2. Time to microbiological clearance
[ Time Frame: 60 days ]

To compare time to microbiological clearance. Microbiological clearance is defined as two consecutive MRSA negative blood cultures.
3. Rates of nephrotoxicity
[ Time Frame: 60 days ]

To evaluate nephrotoxicity in both treatment arms. Nephrotoxicity will be defined as an increase in the serum creatinine level of 50umol/L from baseline or 50% above baseline throughout the course of the study, in the absence of an alternative explanation.
4. Rates of musculoskeletal toxicity
[ Time Frame: 60 days ]

To evaluate musculoskeletal toxicity in both treatment arms as defined by a rise in creatine kinase of 5 times the upper limit of normal during the course of the study.
5. The need to stop the study drug due to toxicity
[ Time Frame: 60 days ]

To evaluate the need to stop the study drug due to toxicity (as defined by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE)
6. The need to discontinue study drug due to worsening infection
[ Time Frame: 60 days ]

To evaluate the need to discontinue study drug due to worsening infection while on study treatment.
7. The need for an additional anti-MRSA agent due to worsening infection while on study treatment.
[ Time Frame: 60 days ]

To evaluate the need for an additional anti-MRSA agent due to worsening infection while on study treatment.
8. Adverse events in both treatment arms up to 60 days from index culture or 30 days post last study dose if later than the 60 day visit.
[ Time Frame: 90 days ]

To compare adverse events in both treatment arms up to 60 days from index culture or 30 days post last study dose if later than the 60 day visit.
9. Serious adverse events at any time during the study period, whether or not they are thought to be related to the investigation drug.
[ Time Frame: 60 days ]

To assess the occurrence of serious adverse events at any time during the study period, whether or not they are thought to be related to the investigation drug.
Other Outcome Measures:
1. All cause mortality in the different subtypes of bacteremia
[ Time Frame: 60 days ]

To compare rates of all-cause mortality 60 days from the time of index blood culture of daptomycin treatment versus vancomycin treatment in the following subtypes of bacteremia (as per the patient's final diagnosis) defined as follows:

  1. Uncomplicated bacteremia
  2. Complicated bacteremia without endocarditis
  3. Right- sided endocarditis
  4. Left sided endocarditis
2. Rates of clinical failure in the different subtypes of bacteremia
[ Time Frame: 60 days ]

To compare rates of clinical failure of daptomycin treatment versus vancomycin treatment in the following subtypes of bacteremia (as per the patient's final diagnosis) defined as follows:

  1. Uncomplicated bacteremia
  2. Complicated bacteremia without endocarditis
  3. Right- sided endocarditis
  4. Left sided endocarditis
Open or close this module Eligibility
Minimum Age: 21 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
    1. .Isolation of a significant organism other than MRSA from index blood cultures or blood cultures taken up to two weeks prior to enrolment and/or for which the patient is still on treatment.
    2. .Chest x-ray at baseline consistent with pneumonia AND at least 2 of the following signs and symptoms: New onset or worsening cough, purulent sputum or increased suctioning requirements, dyspnea/tachypnea or respiratory rate > 30/min, hypoxemia or worsening gas exchange as determined by study investigator.)
Open or close this module Contacts/Locations
Central Contact Person: Thuan Tong Tan, MBBS, PhD
Telephone: +65-63213479
Email: tan.thuan.tong@sgh.com.sg
Central Contact Backup: Shirin Kalimuddin, MBBS, MRCP
Telephone: +65-63213479
Email: shirin.kalimuddi@sgh.com.sg
Study Officials: Thuan Tong Tan, MBBS, PhD
Principal Investigator
Singapore General Hospital
Locations: Singapore
Singapore General Hospital
Singapore, Singapore, 169608
Contact:Contact: Thuan Tong Tan, MBBS,PhD +65-63213479 tan.thuan.tong@sgh.com.sg
Contact:Contact: Shirin Kalimuddin, MBBS, MRCP +65-63213479 shirin.kalimuddin@sgh.com.sg
Contact:Principal Investigator: Thuan Tong Tan, MBBS, PhD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services