Staphylococcus Aureus Bacteremia Clinical Trial
— CERTOfficial title:
Combination Cefazolin With Ertapenem for Methicillin-susceptible Staphylococcus Aureus Bacteremia (CERT)
NCT number | NCT04886284 |
Other study ID # | 2021-7400 |
Secondary ID | |
Status | Recruiting |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | May 20, 2024 |
Est. completion date | July 2025 |
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)
Status | Recruiting |
Enrollment | 60 |
Est. completion date | July 2025 |
Est. primary completion date | April 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility | 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: 1. Adult >=18 years old 2. S. aureus bacteremia within the past 48 hours: - with any unknown MRSA status (in centers with <15% prevalence of MRSA in their annual blood cultures) or known negative MRSA screening swab within 90 days OR - which has already been shown to be MSSA 3. Current receipt of cefazolin or where it would be clinically appropriate (according to treating ID specialist) to switch to cefazolin as the backbone therapy (open label, non-study drug). 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: 1. At time of recruitment, the patient has already clinically improved with at least one subsequent negative culture at >24 hours incubation 2. Anaphylaxis to any beta-lactam antibiotic (and any allergy to ertapenem) Polymicrobial bacteremia (not including skin commensals) 3. Known seizure disorder 4. Any receipt of valproic acid 5. Expected mortality within 48 hours 6. Need for critical care resources but "do not resuscitate" status precludes the receipt of critical care 7. Unable to provide informed consent and no available healthcare proxy (with ethics approval for deferred consent in cases of severe illness) Administrative: 1. Refusal to provide informed consent 2. Refusal of healthcare team to participate 3. No reliable means of outpatient contact (telephone/email/text) 4. Previously enrolled 5. Patients whose isolate is identified as MRSA post-enrollment will be subsequently excluded (see below). 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. |
Country | Name | City | State |
---|---|---|---|
Canada | McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital) | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
Todd C. Lee MD MPH FIDSA |
Canada,
Bamberger DM, Herndon BL, Fitch J, Florkowski A, Parkhurst V. Effects of neutrophils on cefazolin activity and penicillin-binding proteins in Staphylococcus aureus abscesses. Antimicrob Agents Chemother. 2002 Sep;46(9):2878-84. doi: 10.1128/AAC.46.9.2878-2884.2002. — View Citation
Chambers HF, Sachdeva M. Binding of beta-lactam antibiotics to penicillin-binding proteins in methicillin-resistant Staphylococcus aureus. J Infect Dis. 1990 Jun;161(6):1170-6. doi: 10.1093/infdis/161.6.1170. — View Citation
Cheng MP, Lawandi A, Butler-Laporte G, De l'Etoile-Morel S, Paquette K, Lee TC. Adjunctive Daptomycin in the Treatment of Methicillin-susceptible Staphylococcus aureus Bacteremia: A Randomized, Controlled Trial. Clin Infect Dis. 2021 May 4;72(9):e196-e203. doi: 10.1093/cid/ciaa1000. — View Citation
Cosgrove SE, Vigliani GA, Fowler VG Jr, Abrutyn E, Corey GR, Levine DP, Rupp ME, Chambers HF, Karchmer AW, Boucher HW. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009 Mar 15;48(6):713-21. doi: 10.1086/597031. — View Citation
Sakoulas G, Olson J, Yim J, Singh NB, Kumaraswamy M, Quach DT, Rybak MJ, Pogliano J, Nizet V. Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6609-6618. doi: 10.1128/AAC.01192-16. Print 2016 Nov. — View Citation
Tong SYC, Mora J, Bowen AC, Cheng MP, Daneman N, Goodman AL, Heriot GS, Lee TC, Lewis RJ, Lye DC, Mahar RK, Marsh J, McGlothlin A, McQuilten Z, Morpeth SC, Paterson DL, Price DJ, Roberts JA, Robinson JO, van Hal SJ, Walls G, Webb SA, Whiteway L, Yahav D, Davis JS; Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe. Clin Infect Dis. 2022 Nov 30;75(11):2027-2034. doi: 10.1093/cid/ciac476. Erratum In: Clin Infect Dis. 2023 Apr 17;76(8):1532-1533. — View Citation
Ulloa ER, Singh KV, Geriak M, Haddad F, Murray BE, Nizet V, Sakoulas G. Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia. Clin Infect Dis. 2020 Sep 12;71(6):1413-1418. doi: 10.1093/cid/ciz995. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Health-related quality of life | This will be assessed using the EQ-5D-5L questionnaire | 90 days | |
Primary | Clinical success | Composite of: Patient alive, fever resolved, blood cultures negative for S. aureus, systolic blood pressure >=90mmHg not on vasopressors | Day 5 | |
Secondary | Blood culture clearance | Time between first positive and first negative blood culture | 30 days | |
Secondary | 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 | 30 days | |
Secondary | Length of stay | The time from initial emergency room visit until discharge from hospital in patients discharged alive | 90 days | |
Secondary | All cause-mortality | Death from any cause | 90 days | |
Secondary | C. diff infection | Any C. difficile infection within 56 days | 56 days | |
Secondary | Gram-negative bacteremia | Any Gram-negative bacteremia within 56 days | 56 days | |
Secondary | New colonization with carbapenemase producing organisms | Newly identified colonization with carbapenemase producing organisms to day 56 | 56 days | |
Secondary | Valve replacement surgery | Any valve replacement surgery occurring after the initial diagnosis | 56 days | |
Secondary | 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 | Between Days 6 and 90 inclusive | |
Secondary | Seizure | Any clinically identified seizure within 48 hours of discontinuation of combination therapy | 7 days | |
Secondary | 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 | 7 days |
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