Treatment Algorithm to Reduce the Use of Vancomycin in Adults With Blood Stream Infection

Condition(s) targeted: Bacteremia

Intervention: Vancomycin (Drug); Vancomycin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Vance Fowler, MD, Principal Investigator, Affiliation: Duke University

Overall contact:
Suzanne Aycock, MSN, PMP, Phone: 919-668-8046, Email: suzanne.aycock@duke.edu

The purpose of this study is to accurately determine the length of appropriate drug treatment for staphylococcal blood stream infection. The study seeks to address important information about the management of staphylococcal blood stream infections.

Official title: A Multi-Center, Randomized, Open-Label, Comparative Study to Assess the Safety and Efficacy of a Treatment Algorithm to Reduce the Use of Vancomycin in Adult Patients With Blood Stream Infections Due to Staphylococci

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Compare cure rate between algorithm and standard of care therapy

Evaluate safety of algorithm-based therapy

Secondary outcome: Antibiotic days by treatment group

Detailed description: To demonstrate that the clinical efficacy of algorithm-based therapy of patients with staphylococcal blood stream infection is noninferior to current standard of care.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Provide signed and dated informed consent. The patient's legally authorized representative (LAR) can provide a signed informed consent for the patient if allowed by local Institutional Review Board/Ethics Committee (IRB/EC) policy. 2. Is ≥ 18 yrs of age. 3. If the subject has an intravenous catheter in place then the subject and his/her primary health care provider must agree to have the catheter removed within 5 days of the initial blood culture draw with the exception of those subjects who meet criteria for simple CoNS bacteremia as defined in Table 1. The catheter may be retained in those subjects with simple CoNS bacteremia. 4. Has blood stream infection defined as at least one blood culture positive for S. aureus or CoNS. In most cases, vancomycin(or other study drug alternative) will have been started prior to randomization. Enrollment windows depend on speciation and clinical classification as follows: 1. identification of CoNS and classification as simple per Table 1-must be randomized within 3 calendar days of the start of treatment effective for the baseline infecting pathogen 2. identification of CoNS and classification as uncomplicated per Table 1 must be randomized within 4 calendar days of the start of treatment effective for the baseline infecting pathogen

3. identification of S. aureus - must be randomized within 12 calendar days of the

start of treatment effective for the baseline infecting pathogen 5. This criterion has been removed 6. Women of child bearing potential must have a negative urine and/or serum pregnancy test. 7. All patients of reproductive potential must be abstinent or agree to use double-barrier contraception while receiving study (algorithm based or Standard of Care) therapy. Exclusion Criteria: 1. Has known or suspected new complicated staphylococcal infection at the time of enrollment. 2. Weigh ≥ 200 kg. 3. Has non-removable intravascular foreign material at the time a positive blood culture was drawn (e. g., intracardiac pacemaker or cardioverter/defibrillator wires, hemodialysis access grafts, cardiac prosthetic valve, valvular support ring). Exception: coronary stents, inferior vena cava (IVC) filters in place > 6 weeks, patients with pacemakers whose baseline infecting pathogen is a CoNS, vascular stents in place for > 6 weeks, non-hemodialysis grafts in place >90 days and hemodialysis grafts not used within past 12 months and not previously infected are eligible for randomization. Arthroplasties and other extravascular devices, e. g. synthetic hernia repair mesh, and non-arthroplasty orthopedic prostheses including pins or plates, are acceptable as long as there are no signs or symptoms of foreign material-related infection at the time of randomization. 4. This criterion has been removed 5. Has a moribund clinical condition such that there is a high likelihood of death or cardiac surgery during the next three days. 6. Has shock or hypotension (supine systolic blood pressure < 80 mmHg) or oliguria (urine output < 20 mL/h) unresponsive to fluids or pressors within four hours. 7. Has received an investigational antibacterial agent with anti-staphylococcal activity within 30 days prior to randomization. 8. Has a documented history of significant allergy or intolerance to all protocol-approved antibiotics anticipated to be effective for their infection. 9. Has an infecting pathogen with confirmed reduced susceptibility to vancomycin (Minimum Inhibitory Concentrations (MIC) > 2 µg/mL) if known. Note: If reduced susceptibility to vancomycin is discovered after enrollment, the patient will be treated with daptomycin (if pathogen is susceptible). Patient will remain in study as appropriate and be evaluated in the Intent to Treat (ITT) analysis, but will be excluded from Protocol Population (PP) analyses. 10. For S. Aureus patients, is severely neutropenic (absolute neutrophil count < 0. 100x103/mm3) or is anticipated to develop severe neutropenia (absolute neutrophil count < 0. 100x103/ mm3) during the study treatment period due to prior or planned chemotherapy. CoNS patients with neutropenia are eligible to be enrolled. 11. This criterion has been removed 12. Has previously known Human Immunodeficiency Virus (HIV) infection with a nadir CD4+ count of <100 cells/mm3 within the past 12 months 13. Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations. 14. Is pregnant or trying to get pregnant, nursing, or lactating. 15. Has known or suspected septic arthritis, osteomyelitis, pneumonia or other metastatic focus of infection. CoNS patients with pneumonia and not being treated or anticipated to start treatment with antibiotics effective for the baseline infecting pathogen can be included 16. Has polymicrobial blood stream infection including at least one non-staphylococcal species, except AFTER consultation with the Clinical Medical Monitor at DCRI. Note that it is possible that a subject may not have a known polymicrobial bloodstream infection at the time of randomization, but additional pathogen(s) can subsequently be isolated from the initial blood culture. These patients will be eligible to remain in the trial. Please also note that patients with S. aureus plus CoNS will follow the treatment pathway for S. aureus. 17. This criterion has been removed. 18. Is hemodialysis dependent or has end stage renal disease (Creatinine Clearance (CrCl) < 30 cc/min). 19. Developed Staphylococcus aureus blood stream infection within 72 hours of percutaneous coronary revascularization 20. Received of any of the following antibiotics for 7 or more of the 10 calendar days immediately preceding the calendar day that the initial positive blood culture was drawn: 1. If methicillin susceptibility of the isolate is unknown at the time of enrollment: vancomycin; daptomycin; telavancin; tigecycline; linezolid (in either oral or IV administration); quinupristin/dalfopristin; piperacillin/tazobactam; penicillin; nafcillin; oxacillin; cloxacillin; cefazolin, ceftriaxone, ceftaroline, dalbavancin, oritavancin, tedizolid, and levofloxacin or equivalent fluoroquinolone (in either oral or IV administration) Note: ciprofloxacin is not an exclusion criteria. 2. If the staphylococcal isolate is known to be methicillin resistant: vancomycin; daptomycin; telavancin; tigecycline; linezolid (in either oral or IV administration), quinupristin/dalfopristin, dalbavancin, oritavancin, tedizolid, and ceftaroline. Note: patients who have developed bacteremia after at least 7 days of prophylaxis with oral antibiotics have by definition failed prophylaxis and the oral antibiotic can be deemed non-effective for the index bacteremia. Oral antibiotics that have failed as prophylaxis in this manner will not be considered exclusionary or count towards the number of antibiotic days but must be stopped upon randomization 21. Has previously participated in this study.

Suzanne Aycock, MSN, PMP, Phone: 919-668-8046, Email: suzanne.aycock@duke.edu

Fundacio Clinic Privada per a la Recera, Barcelona 08036, Spain; Recruiting
Ana Del Rio, Phone: +34-93-227-5400, Email: miro97@fundsoriano.es
Jose M Miro, MD, PhD, Principal Investigator

University of Alabama, Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Sherree Wright, RN, Phone: 205-934-2186, Email: sherree@uab.edu
John Baddley, MD, Principal Investigator

David Geffen School of Medicine UCLA, Los Angeles, California 90095, United States; Not yet recruiting
Zachary Rubin, MD, Phone: 910-794-0187, Email: ZRubin@mednet.ucla.edu
Zachary Rubin, MD, Principal Investigator

University of Colorado, Denver, Colorado 80204, United States; Not yet recruiting
Timothy Jenkins, MD, Phone: 303-602-5041, Email: timothy.jenkins@dhha.org
Timothy Jenkins, MD, Principal Investigator

University of Mass, Worcester, Massachusetts 01752, United States; Recruiting
Jennifer Daly, MD, Phone: 508-856-4060, Email: jennifer.daly@umassmemorial.org
Jennifer Daly, MD, Principal Investigator

Henry Ford Hospital, Detroit, Michigan 48202, United States; Recruiting
Marcus Zervos, MD, Phone: 313-916-2573, Email: mzervos1@hfhs.org
Marcus Zervos, MD, Principal Investigator

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States; Recruiting
Jennifer Cavalieri, Phone: 402-559-3243, Email: rcavalieri@unmc.edu
Mark Rupp, MD, Principal Investigator

Albert Einstein College of Medicine, Bronx, New York 10467, United States; Recruiting
Paul Riska, MD, Phone: 718-920-6494, Email: priska@montefiore.org
Paul Riska, MD, Principal Investigator

Carolina Medical Center, Charlotte, North Carolina 28207, United States; Recruiting
James Horton, MD, Phone: 704-335-3823, Email: James.Horton@carolinahealthcare.org
James Horton, MD, Principal Investigator

Duke University Medical Center, Durham, North Carolina 27705, United States; Recruiting
Vivian Chu, MD, Phone: 919-668-7174, Email: vivian.chu@duke.edu
Vivian Chu, MD, Principal Investigator

Brody School of Medicine at ECU, Greenville, North Carolina 27834, United States; Not yet recruiting
Paul Cook, MD, Phone: 252-744-4500, Email: cookp@ecu.edu
Paul Cook, MD, Principal Investigator

Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Dannah Wray, MD, Phone: 843-792-4541, Email: wraydw@musc.edu
Dannah Wray, MD, Principal Investigator

Greenville Hospital System, Greenville, South Carolina 29605, United States; Recruiting
Isabel Gillespie, Phone: 864-455-9025, Email: igillespie@ghs.org
John Schrank, MD, Principal Investigator

UT MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Isam Raad, MD, Phone: 713-792-7943, Email: iraad@mdanderson.org
Isam Raad, MD, Principal Investigator

Starting date: February 2011
Last updated: July 2, 2015