Bacteremia Due to Staphylococcus Aureus Clinical Trial
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
Verified date | April 2016 |
Source | Singapore General Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | Singapore: Health Sciences Authority |
Study type | Interventional |
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%.
Status | Terminated |
Enrollment | 14 |
Est. completion date | December 2015 |
Est. primary completion date | December 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 21 Years and older |
Eligibility |
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. - 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. 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.) |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Singapore | Singapore General Hospital | Singapore |
Lead Sponsor | Collaborator |
---|---|
Singapore General Hospital | Singapore Clinical Research Institute |
Singapore,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | All cause mortality in the different subtypes of bacteremia | 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: Uncomplicated bacteremia Complicated bacteremia without endocarditis Right- sided endocarditis Left sided endocarditis |
60 days | No |
Other | Rates of clinical failure in the different subtypes of bacteremia | 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: Uncomplicated bacteremia Complicated bacteremia without endocarditis Right- sided endocarditis Left sided endocarditis |
60 days | No |
Primary | 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 | No |
Secondary | Rates of clinical failure | 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. |
60 days | No |
Secondary | Time to microbiological clearance | To compare time to microbiological clearance. Microbiological clearance is defined as two consecutive MRSA negative blood cultures. | 60 days | No |
Secondary | Rates of nephrotoxicity | 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. | 60 days | Yes |
Secondary | Rates of musculoskeletal toxicity | To evaluate musculoskeletal toxicity in both treatment arms as defined by a rise in creatine kinase (CK) of 5 times the upper limit of normal during the course of the study. | 60 days | Yes |
Secondary | The need to stop the study drug due to toxicity | 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]) | 60 days | Yes |
Secondary | The need to discontinue study drug due to worsening infection | To evaluate the need to discontinue study drug due to worsening infection while on study treatment. | 60 days | No |
Secondary | The need for an additional anti-MRSA agent due to worsening infection while on study treatment. | To evaluate the need for an additional anti-MRSA agent due to worsening infection while on study treatment. | 60 days | No |
Secondary | 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. | 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. | 90 days | Yes |
Secondary | Serious adverse events at any time during the study period, whether or not they are thought to be related to the investigation drug. | 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. | 60 days | Yes |
Status | Clinical Trial | Phase | |
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