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

NCT01191840 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro00025497DMID Protocol Number: 09-0080
• Study Type: interventional
• Target: 509
• Locations: 2 countries
• Sites: 15

Brief Summary

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.

Conditions

Bacteremia

Keywords

staphylococci

Outcome Measures

Primary Outcomes (4)

• Cure Rate

  To compare the cure rate at Test of Cure evaluation, between the proposed treatment algorithm and the standard of care therapy.

  Test of cure 2 (up to approximately 42 days)

• Number of Participants With Serious Adverse Events

  Number of Participants that reported a Serious Adverse Event

  Test of cure 2 (up to approximately 42 days)

• Number of Participants With Adverse Events Leading to Study Drug Withdrawal

  Number of Participants with an Adverse Event leading to study drug withdrawal

  Test of cure 2 (up to approximately 42 days)

• Number of Participants That Changed From Vancomycin to Another Study Antibiotic Due to an Adverse Event

  Patient changes from vancomycin or a protocol-approved study antibiotic to another protocol-approved study antibiotic due to AE associated with study drug

  Test of cure 2 (up to approximately 42 days)

Secondary Outcomes (1)

• Antibiotic Days by Treatment Group

  Test of cure 2 (up to approximately 42 days)

Study Arms (2)

Algorithm-determined therapy

EXPERIMENTAL

Drug: Vancomycin

Standard of Care

ACTIVE COMPARATOR

Drug: Vancomycin

Interventions

Vancomycin DRUG

Duration

Also known as: Nafcillin, Oxacillin, Cloxacillin, Daptomycin, Cefazolin

Algorithm-determined therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Is ≥ 18 yrs of age.
• 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.
• 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:
• 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
• 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
• identification of S. aureus - must be randomized within 12 calendar days of the start of treatment effective for the baseline infecting pathogen
• This criterion has been removed
• Women of child bearing potential must have a negative urine and/or serum pregnancy test.
• 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.

You may not qualify if:

• Has known or suspected new complicated staphylococcal infection at the time of enrollment.
• Weigh ≥ 200 kg.
• 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.
• This criterion has been removed
• Has a moribund clinical condition such that there is a high likelihood of death or cardiac surgery during the next three days.
• 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.
• Has received an investigational antibacterial agent with anti-staphylococcal activity within 30 days prior to randomization.
• Has a documented history of significant allergy or intolerance to all protocol-approved antibiotics anticipated to be effective for their infection.
• 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.
• 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.
• This criterion has been removed
• Has previously known Human Immunodeficiency Virus (HIV) infection with a nadir CD4+ count of \<100 cells/mm3 within the past 12 months
• Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations.
• Is pregnant or trying to get pregnant, nursing, or lactating.
• 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

Sponsors & Collaborators

• Duke University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (15)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

David Geffen School of Medicine UCLA

Los Angeles, California, 90095, United States

Location

University of Colorado

Denver, Colorado, 80204, United States

Location

University of Mass

Worcester, Massachusetts, 01752, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

Carolina Medical Center

Charlotte, North Carolina, 28207, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Brody School of Medicine at ECU

Greenville, North Carolina, 27834, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Greenville Hospital System

Greenville, South Carolina, 29605, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fundacio Clinic Privada per a la Recera

Barcelona, 08036, Spain

Location

Related Publications (1)

• Holland TL, Raad I, Boucher HW, Anderson DJ, Cosgrove SE, Aycock PS, Baddley JW, Chaftari AM, Chow SC, Chu VH, Carugati M, Cook P, Corey GR, Crowley AL, Daly J, Gu J, Hachem R, Horton J, Jenkins TC, Levine D, Miro JM, Pericas JM, Riska P, Rubin Z, Rupp ME, Schrank J Jr, Sims M, Wray D, Zervos M, Fowler VG Jr; Staphylococcal Bacteremia Investigators. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial. JAMA. 2018 Sep 25;320(12):1249-1258. doi: 10.1001/jama.2018.13155.

  PMID: 30264119 DERIVED

MeSH Terms

Conditions

Bacteremia

Interventions

Vancomycin; Nafcillin; Oxacillin; Cloxacillin; Daptomycin; Cefazolin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Cephalosporins; Thiazines

Results Point of Contact

• Title: Vance Fowler
• Organization: Duke University Health System

fowle003@mc.duke.edu

919-668-8044

Study Officials

• Vance Fowler, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2010
• First Posted: August 31, 2010
• Study Start: February 1, 2011
• Primary Completion: March 4, 2017
• Study Completion: March 4, 2017
• Last Updated: January 5, 2018
• Results First Posted: December 12, 2017

Record last verified: 2017-12

Locations

ES (1); US (14)