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Multi-Drug Resistant Organism (MDRO): Study of Highly Resistant Escherichia Coli (SHREC)

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ClinicalTrials.gov Identifier: NCT04574596
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : March 17, 2021
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Duke University

Brief Summary:
This is a prospective, observational, multicenter, case-control study.

Condition or disease Intervention/treatment
E Coli Infection Other: no Intervention

Detailed Description:

This is an observational cohort study. A total of 300 subjects will be enrolled. Cases are defined as unique subjects who have a monomicrobial blood culture positive for growth of 3rd Generation Cephalosporin Resistant Escherichia coli (3GCR-Ec), defined as resistance to ceftriaxone or cefotaxime, during hospitalization. For each case, the next available unique subject from the same study site, with a monomicrobial blood culture positive for growth of 3rd Generation Cephalosporin Sensitive Escherichia coli (3GCS-Ec) during hospitalization will be included as a control. A waiver of informed consent and HIPAA will be requested. This is a minimal risk study without any direct subject contact. In addition, no subject information will be collected that is not part of routine clinical care.

The trigger for enrollment in the study will be the identification in a participating local microbiology laboratory of a 3GCR-Ec in a monomicrobial blood culture. These will be reported to study personnel at the study site, who will evaluate eligibility. If the subject is deemed eligible, the 3GCR-Ec isolate will be saved for shipping to the Laboratory Center, and the isolate also saved at the local laboratory. Sites will be advised to destroy any samples saved at the local laboratory as part of this study at the end of the study. The local microbiology laboratory, or designee, will then identify the next subject available with a 3GCS-Ec in a blood culture. These will also be reported to study personnel for evaluation of eligibility as a control. If the control subject is eligible, the corresponding 3GCS-Ec isolate will be saved for shipping to the Laboratory Center, and the isolate will also be saved at the local laboratory . Sites will be advised to destroy any samples saved at the local laboratory as part of this study at the end of the study.

For cases and controls, clinical data will be collected from the electronic health records (EHR) for up to 30 days after the index blood culture. Data collection will be performed by study personnel at the site into a central, secure, research database.

One E. coli isolate per study subject will be collected from the index blood culture. No other biologic samples will be collected. Data will be entered at or after the 30-day time point. There will be no long-term follow-up for subjects.

Primary Objective:

To evaluate the use of oral step down therapy in subjects with 3GCR-Ec and 3GCS-Ec bacteremia.

Secondary Objectives

  1. To describe the treatment regimens used in subjects with 3GCR-Ec and 3GCS-Ec bacteremia.
  2. To determine the association between duration of intravenous antibiotics and Inverse Probability Weighting (IPW)-adjusted Desirability Of Outcome Ranking (DOOR) outcomes at 30 days
  3. To determine the association between total duration of antibiotics and IPW-adjusted DOOR outcomes at 30 days
  4. To determine risk factors on days 0, 3, 5, and 7 after first positive blood culture for poor outcomes (either DOOR composite score or individual outcomes) at 30 days.

Exploratory Objective:

• To describe phenotypic and genotypic characteristics of bacterial isolates.

This study is minimal risk to study participants, and has no data safety monitoring board.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: MDRO: Study of Highly Resistant Escherichia Coli
Actual Study Start Date : November 12, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
3GCR ceftriaxone-resistant-E. coli
Positive blood culture for above resistant e coli. Observational there will be no intervention
Other: no Intervention
This is an observational study. There is no intervention

3GCS ceftriaxone-susceptible-E. coli
Positive blood culture for above susceptible e coli. Observational there will be no intervention
Other: no Intervention
This is an observational study. There is no intervention




Primary Outcome Measures :
  1. Number of participants who received oral step-down therapy [ Time Frame: Within 30 days of culture collection ]
    Number of participants who received oral-step down therapy for treatment of e. Coli


Secondary Outcome Measures :
  1. Duration of antibiotics [ Time Frame: From culture collection to 30 days post culture collection ]
    Total duration of antibiotics

  2. Duration of intravenous antibiotics [ Time Frame: From culture collection to 30 days post culture collection ]
    Total duration of intravenous antibiotics

  3. Duration of oral antibiotics [ Time Frame: From culture collection to 30 days post culture collection ]
    Total duration of oral antibiotics

  4. Number of participants who received short course antibiotic therapy [ Time Frame: From culture collection to 30 days post culture collection ]
    Number of participants who received short-course antibiotic therapy defined as <= 7 days of antibiotic therapy

  5. Number of participants with ongoing antibiotic treatment at 30 days [ Time Frame: 30 days post culture collection ]
    Number of participants with ongoing antibiotic treatment at 30 days

  6. Number of participants with resolution or improvement of symptoms [ Time Frame: 30 days post culture collection ]
    Number of participants with resolution or improvement of symptoms by 30 days

  7. Number of participants with anatomic source specific symptomatic response [ Time Frame: 30 days post culture collection ]
    Number of participants with anatomic source specific symptomatic response

  8. Discharged by 30 days [ Time Frame: culture collection through 30 days post culture collection ]
    Discharged from the hospital by 30 days

  9. Days to discharge [ Time Frame: culture collection through 30 days post culture collection ]
    Days from culture collection to hospital discharge

  10. Length of stay [ Time Frame: hospital admission through 30 days post culture collection ]
    Days from hospital admission to hospital discharge

  11. Number of participants with a readmission within 30 days of index culture [ Time Frame: culture collection through 30 days post culture collection ]
    Number of participants with a readmission to the same hospital within 30 days of index culture

  12. Number of participants with a new positive blood culture with E. coli within 30 days of index culture [ Time Frame: culture collection through 30 days post culture collection ]
    Number of participants with a new positive blood culture with E. coli within 30 days of index culture

  13. Number of participants with a three-fold or greater increase in serum creatinine from day of index culture [ Time Frame: culture collection through 30 days post culture collection ]
    Number of participants with a three-fold or greater increase in serum creatinine from day of index culture

  14. Number of participants with a newly required renal replacement therapy post index culture [ Time Frame: culture collection through 30 days post culture collection ]
    Number of participants with a newly required renal replacement therapy post index culture

  15. Number of participants with a Clostridioides difficile infection [ Time Frame: culture collection through 30 days post culture collection ]
    Number of participants with a Clostridioides difficile infection

  16. Mortality at 30 days [ Time Frame: culture collection through 30 days post culture collection ]
    Mortality at 30 days

  17. Number of participants in the ICU on day 0, 3, 5, and 7 [ Time Frame: Days 0, 3, 5, 7 ]
    Number of participants in the ICU on day 0, 3, 5, and 7

  18. Desireability of Outcome Ranking (DOOR) outcome at 30 days [ Time Frame: 30 days post culture collection ]

    The desirability of outcome ranking (DOOR) in this study will assess three deleterious events (lack of clinical response, unsuccessful discharge, and undesirable events) in addition to survival at 30 days after the index culture. The five ordered levels of the variable, from best to worst, are:

    1. Alive without deleterious events
    2. Alive with 1 deleterious event
    3. Alive with 2 deleterious events
    4. Alive with 3 deleterious events
    5. Death by 30 days

    The undesirable events are:

    • Post-culture renal failure
    • Clostridioides difficile infection


Other Outcome Measures:
  1. Antibiotic resistance phenotype [ Time Frame: Day 0, which is the date of culture collection in this observational study ]
    Antibiotic resistance phenotype

  2. Antimicrobial resistance genes [ Time Frame: Day 0, which is the date of culture collection in this observational study ]
    Antimicrobial resistance genes

  3. Duration of individual antibiotics and specific combinations of antibiotics [ Time Frame: culture collection through 30 days post culture collection ]
    Duration of individual antibiotics and specific combinations of antibiotics


Biospecimen Retention:   Samples Without DNA

3GCRceftriaxone-resistant-E. coli in blood culture

Control group 3GCSceftriaxone-susceptible-E. coli in a blood culture :



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
  • Sample size: 300 total: 150 3GCR-Ec cases, 150 3GCS-Ec controls.
  • This is a consecutive cohort study without age or gender exclusions. Special populations such as women, children, and minorities will be included.
  • The study population will be drawn from subjects who are hospitalized at participating study hospitals.
  • This observational study is minimal-risk and will be performed under a waiver of consent and HIPAA.
Criteria

Inclusion criteria:

  1. Positive monomicrobial blood culture for 3GCR-Ec (cases) or 3GCS-Ec (control)
  2. Hospitalized at the time of obtaining index blood culture OR in the emergency department at the time of obtaining index blood culture, if followed by hospitalization within 72 hours

Exclusion criteria:

  1. Previously included in this study as either control or case subject
  2. Previous blood culture positive for E. coli during the current hospitalization
  3. In vitro non-susceptibility to any carbapenem tested in the local clinical microbiology laboratory
  4. Evidence of carbapenemase production in the E. coli isolate of interest as determined by the local clinical microbiology laboratory

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04574596


Contacts
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Contact: Minal Bhojani, MBA, MS 919-668-8134 minal.bhojani@duke.edu
Contact: Beth Evans 919-668-8247 beth.evans@duke.edu

Locations
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United States, California
Harbor-University of California Los Angeles Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Loren Miller         
United States, Colorado
University of Colorado Denver Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Martin Krsak         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jesse Jacob         
United States, Louisiana
Ochsner Medical Center Recruiting
New Orleans, Louisiana, United States, 21287
Contact: Julia Garcia-Diaz         
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Pranita Tamma         
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Keith Kaye         
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Erica Herc         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Charles Huskins         
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Michael Satlin         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: David van Duin         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106-7282
Contact: Elie Saade         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Yohei Doi         
United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Cesar Arias         
Sponsors and Collaborators
Duke University
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Study Director: Vance G. Fowler, MD Duke Clinical Research Institute
Principal Investigator: David van Duin, MD, PhD University of North Carolina
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04574596    
Other Study ID Numbers: Pro00106280
UM1AI104681 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
Extended Spectrum β-Lactamases (ESBL)
Additional relevant MeSH terms:
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Escherichia coli Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections