A Phase 2 interventional study of Ertapenem and Placebo in Staphylococcus Aureus Bacteremia, Staphylococcus Aureus Septicemia and Staphylococcal Sepsis, sponsored by Todd C. Lee MD MPH FIDSA. Recruiting at 8 sites in Canada. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by Todd C. Lee MD MPH FIDSA · Phase 2, Interventional, and Treatment
There is a variety of in vitro, in vivo (animal model), and human case series data which suggests that the addition of ertapenem to cefazolin could improve outcomes in methicillin-susceptible S. aureus bacteremia. No randomized controlled trial has been performed.
This study is an approved sub-study of The Staphylococcus aureus Network Adaptive Platform (SNAP) trial (NCT05137119)
Cefazolin is licensed in Canada for the management of infections due to susceptible Staphylococcus aureus, including bacteremia. It has been commonly used for decades in this disease and, when compared in observational studies to anti-staphylococcal penicillins, has demonstrated reduced mortality.
Nevertheless, in the treatment of methicillin-susceptible S. aureus (MSSA) bacteremia, there remains significant opportunities to improve clinical outcomes. Indeed, S. aureus bacteremia kills more Canadians annually than myeloma, melanoma, renal, ovarian or stomach cancers. Overall mortality approached 18% in a recent Canadian clinical trial performed by our group (Cheng et al, 2020).
The duration of bacteremia, particularly after antibiotherapy is recognized as a major risk factor for mortality. Interventions which reduce the duration of bacteremia, without increasing the frequency of renal failure like gentamicin (Cosgrove et al, 2009) or the combination of vancomycin and flucloxacillin in MRSA (Tong et al, 2020), are among the most promising candidates for larger phase 3 studies designed to impact patient mortality.
Ertapenem is a commonly used antibiotic which has been on the Canadian market for more than 15 years. It is most commonly used in patients with infections caused by extended-spectrum beta-lactamase producing Enterobacteraciae; however, it has a broad spectrum of activity including Gram-positive bacteria such as S. aureus. Indeed, the drug is licensed in Canada for the treatment of complicated skin and soft tissue infections commonly caused by S. aureus.
In S. aureus the carbapenem antibiotics like ertapenem have exceptional affinity to the essential penicillin-binding protein (PBP), PBP1, exceeding even that of the antistaphylococcal β-lactams (Chambers et al, 1990). This complements the relative PBP2 proclivity of cefazolin (Bamberger et al, 2002).
The combination of cefazolin with ertapenem has also been shown to be synergistic in vitro (Sakoulas et al, 2016), in vivo in the mouse and rat models (Sakoulas et al, 2016; Ulloa et al, 2020), and in a small human case series (Ulloa et al, 2020).
Based on this data, there is compelling theory (attack on 2 PBPs), in vitro, in vivo, and human case evidence to support an exploratory phase 2 RCT of cefazolin-ertapenem for the treatment of MSSA bacteremia.
303 studies on the registry are indexed under Staphylococcal Infections; 34 are open to participants now.
This study's planned enrollment of 60 is below the median of 124 across 198 interventional studies indexed under Staphylococcal Infections.
Browse Staphylococcal Infections studies →Todd C. Lee MD MPH FIDSA is the lead sponsor of 5 studies on the registry; 4 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The participant must fulfil all inclusion and exclusion criteria for the SNAP Platform (NCT05137119) and also the following inclusion and exclusion criteria to be eligible for this sub-study:
Inclusion Criteria:
S. aureus bacteremia within the past 48 hours:
NOTE: Up to an additional 12-24 hours of open label non-study VANCOMYCIN, LINEZOLID or DAPTOMYCIN may be allowed if there is sepsis and clinical concern for MRSA has not been excluded.
Exclusion Criteria:
Clinical:
Administrative:
Note that because MSSA is much more common than MRSA in Canada (90% of all S. aureus bacteremia at MUHC, for example, are MSSA and in the presence of a negative MRSA screening swab or unknown MRSA status, this means that the risk of MRSA is less than 5%). We believe time to combination therapy is likely linked to benefit, therefore we will recruit the patients as soon as S. aureus is identified but potentially prior to confirmation the organism is MSSA. Where possible, rapid MRSA detection techniques will be deployed; however with conventional screening this will mean approximately a 12-24 hours delay. Organisms subsequently identified as MRSA will be excluded from the intention to treat analysis and the sample size will be adjusted accordingly to ensure the total enrollment meets study goals.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ertapenem 1g IV daily infused over 2 hours x 5 days
Drug: Ertapenem
Saline placebo infused daily over 2 hours x 5 days
Drug: Placebo
Adjunctive ertapenem
Also known as: Invanz
Saline placebo
Clinical success
Composite of: Patient alive, fever resolved, blood cultures negative for S. aureus, systolic blood pressure \>=90mmHg not on vasopressors
Time frame: Day 5
Blood culture clearance
Time between first positive and first negative blood culture
Time frame: 30 days
Clinical improvement
Time to clinical improvement defined as the time until fever resolved, blood cultures sterile, and systolic blood pressure \>=90mmHg not on vasopressors in patients who survive to clinical improvement
Time frame: 30 days
Length of stay
The time from initial emergency room visit until discharge from hospital in patients discharged alive
Time frame: 90 days
All cause-mortality
Death from any cause
Time frame: 90 days
C. diff infection
Any C. difficile infection within 56 days
Time frame: 56 days
Gram-negative bacteremia
Any Gram-negative bacteremia within 56 days
Time frame: 56 days
New colonization with carbapenemase producing organisms
Newly identified colonization with carbapenemase producing organisms to day 56
Time frame: 56 days
Valve replacement surgery
Any valve replacement surgery occurring after the initial diagnosis
Time frame: 56 days
Recurrent isolation of MSSA from a sterile site
Any positive culture of MSSA from a sterile site (blood, cerebral spinal fluid, joint aspirate, bone, etc.) occurring after the end of combination therapy
Time frame: Between Days 6 and 90 inclusive
Seizure
Any clinically identified seizure within 48 hours of discontinuation of combination therapy
Time frame: 7 days
Acute Kidney Injury
An increase in serum creatinine to ≥1.5 times baseline OR new requirement for hemodialysis at any time in the first 7 days from randomization
Time frame: 7 days
Health-related quality of life
This will be assessed using the EQ-5D-5L questionnaire
Time frame: 90 days
Plan to share: No
Started May 2024 (actual). Primary completion is estimated for Apr 2027, 35 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Ertapenem
Todd C. Lee MD MPH FIDSA