BacteremiaPhase 2BacteremiaNCT01191840
Treatment Algorithm to Reduce the Use of Vancomycin in Adults With Blood Stream Infection
A Phase 2 study testing Vancomycin in people with Bacteremia, run by Duke University at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacteremia
- What is being tested?
- Vancomycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 509 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Feb 2011to 4 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
- 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.
- This criterion has been removed.
- Is hemodialysis dependent or has end stage renal disease (Creatinine Clearance (CrCl) < 30 cc/min).
- Developed Staphylococcus aureus blood stream infection within 72 hours of percutaneous coronary revascularization
- 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:
- 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.
- 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
- Has previously participated in this study.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
University of Alabama, Birmingham
Birmingham, Alabama, 35294
Medical University of South Carolina
Charleston, South Carolina, 29425
Carolina Medical Center
Charlotte, North Carolina, 28207
University of Colorado
Denver, Colorado, 80204
Henry Ford Hospital
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27705
Brody School of Medicine at ECU
Greenville, North Carolina, 27834
Greenville Hospital System
Greenville, South Carolina, 29605
UT MD Anderson Cancer Center
Houston, Texas, 77030
David Geffen School of Medicine UCLA
Los Angeles, California, 90095
University of Nebraska Medical Center
Omaha, Nebraska, 68198
William Beaumont Hospital
Royal Oak, Michigan, 48073
Albert Einstein College of Medicine
The Bronx, New York, 10467
University of Mass
Worcester, Massachusetts, 01752
About this study
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
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.
Read the 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.
PP (per protocol) population: randomized patients EXCLUDING those that: Received a PENS antibiotic -Did not undergo removal of intravascular catheter suspected to be infected. Note that patients with simple CoNS bacteremia may retain the catheter; all other patients should have their catheter(s) removed. -Had blood stream infection with a vancomycin-resistant staphylococcus; or a staphylococcus resistant to protocol-identified alternative drugs if these were used -Discontinued study medication prematurely for reasons other than clinical failure -Did not undergo final TOC assessment -Did not comply with all Patient Inclusion Criteria -Violated any Patient Exclusion Criteria
- Died within 3 days of randomization
- Were classified as non-evaluable
PPE Population: Patients from the PP population who did not have complicated staphylococcal infection.
- Conditions
- Bacteremia
- Being tested
- Vancomycin
- Keywords
- staphylococci
- Medical subject headings
- Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinDrug
Also called Nafcillin, Oxacillin, Cloxacillin, Daptomycin
Duration
VancomycinDrug
Also called Nafcillin, Oxacillin, Cloxacillin, Daptomycin
Duration
| Study group | Role | What they receive |
|---|---|---|
| Algorithm-determined therapy | Experimental | Not described Receives: Drug: Vancomycin |
| Standard of Care | Active comparator | Not described Receives: Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cure Rate
To compare the cure rate at Test of Cure evaluation, between the proposed treatment algorithm and the standard of care therapy.
Measured: 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
Measured: 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
Measured: 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
Measured: Test of cure 2 (up to approximately 42 days)
Secondary outcomes (1)
Antibiotic Days by Treatment Group
This will be analyzed by evaluating the difference in antibiotic days by treatment group and calculating 95% confidence intervals around the difference in antibiotic days among study patients randomized to algorithm-based treatment vs. among study patients randomized to standard treatment.
Measured: Test of cure 2 (up to approximately 42 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startFeb 2011
- Primary completion4 Mar 2017
- Study completion4 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BacteremiaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 509 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Vance Fowler, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01191840
- Sponsor's protocol ID
- Pro00025497
- Other IDs
- DMID Protocol Number: 09-0080
- Acronym
- Bacteremia
- Status last verified
- Dec 2017
- First submitted
- 28 Aug 2010
- Last updated
- 5 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30264119
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01191840
- Acronym / sponsor ID
- Bacteremia / Pro00025497
- Conditions
- Bacteremia
- Keywords
- staphylococci
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 509 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Feb 2011
- Primary completion
- 4 Mar 2017 (actual)
- Study completion
- 4 Mar 2017 (actual)
- First posted
- 31 Aug 2010 (estimated)
- Results
- Posted 12 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
PP (per protocol) population: randomized patients EXCLUDING those that: Received a PENS antibiotic -Did not undergo removal of intravascular catheter suspected to be infected. Note that patients with simple CoNS bacteremia may retain the catheter; all other patients should have their catheter(s) removed. -Had blood stream infection with a vancomycin-resistant staphylococcus; or a staphylococcus resistant to protocol-identified alternative drugs if these were used -Discontinued study medication prematurely for reasons other than clinical failure -Did not undergo final TOC assessment -Did not comply with all Patient Inclusion Criteria -Violated any Patient Exclusion Criteria
- Died within 3 days of randomization
- Were classified as non-evaluable
PPE Population: Patients from the PP population who did not have complicated staphylococcal infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Algorithm-determined therapy | Experimental | Drug: Vancomycin |
| Standard of Care | Active comparator | Drug: Vancomycin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- This criterion has been removed
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VancomycinAlso: Nafcillin, Oxacillin, Cloxacillin, DaptomycinDuration | Drug | Algorithm-determined therapy |
| VancomycinAlso: Nafcillin, Oxacillin, Cloxacillin, DaptomycinDuration | Drug | Standard of Care |
Primary outcome
Cure Rate
Time frame: Test of cure 2 (up to approximately 42 days)
To compare the cure rate at Test of Cure evaluation, between the proposed treatment algorithm and the standard of care therapy.
Number of Participants With Serious Adverse Events
Time frame: Test of cure 2 (up to approximately 42 days)
Number of Participants that reported a Serious Adverse Event
Number of Participants With Adverse Events Leading to Study Drug Withdrawal
Time frame: Test of cure 2 (up to approximately 42 days)
Number of Participants with an Adverse Event leading to study drug withdrawal
Number of Participants That Changed From Vancomycin to Another Study Antibiotic Due to an Adverse Event
Time frame: Test of cure 2 (up to approximately 42 days)
Patient changes from vancomycin or a protocol-approved study antibiotic to another protocol-approved study antibiotic due to AE associated with study drug
1 secondary outcome
Antibiotic Days by Treatment Group
Time frame: Test of cure 2 (up to approximately 42 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30264119Holland 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vance Fowler, MD principal investigator
Duke University
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vancomycin in people with Bacteremia, run by Duke University at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cure Rate (time frame: Test of cure 2 (up to approximately 42 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01191840, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2018.