Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to Extended-spectrum Beta-lactamase (ESBL) or Carbapenemase-producing Enterobacteriaceae: an Observational Multinational Study (INCREMENT)

This study is currently recruiting participants.

Verified February 2013 by Spanish Network for Research in Infectious Diseases

Sponsor:

Information provided by (Responsible Party):

JESUS RODRIGUEZ BAÑO, Spanish Network for Research in Infectious Diseases

ClinicalTrials.gov Identifier:

NCT01764490

First received: December 26, 2012

Last updated: February 16, 2013

Last verified: February 2013

History of Changes

Purpose

Main objective: to observationally assess the efficacy of different antimicrobials in Bloodstream Infection (BSI) due to Enterobacteriaceae producing ESBLs or carbapenemases.

Specific objectives:

Bacteraemic infections due to ESBL-producing Enterobacteriaceae:

To demonstrate that β-lactam/β-lactam inhibitors are not associated with worse cure rate and mortality than carbapenems after controlling for confounders, both as empirical and definitive therapy.
To demonstrate that fluoroquinolones as definitive therapy are not associated with worse cure rate and mortality than carbapenems after controlling for confounders.
To demonstrate that empirical cephalosporins in monotherapy are associated with worse cure rate and mortality than carbapenems after controlling for confounders in infections others than urinary tract infections.
To demonstrate that the association of active aminoglycosides with cephalosporins or fluoroquinolines is not associated with worse cure rate and mortality than carbapenems after controlling for confounders.
To demonstrate that combination empirical and definitive therapy is not associated with better cure rate than monotherapy after controlling for confounders.
For tigecycline, colistin, and fosfomycin, no hypothesis. The objective is to provide adjusted estimations of their association with outcome variables in comparison with carbapenem monotherapy according to clinical situation and infection.

Bacteraemic infections due to carbapenemase-producing Enterobacteriaceae:

To demonstrate that combination therapy is associated with worse cure rate and mortality than monotherapy after controlling for confounders.
To show that carbapenems are associated with worse cure rate and mortality when used in infections other than urinary tract caused by isolates showing MIC <2 µg/mL for imipenem or meropenem in comparison to those caused by isolates with higher MIC, after controlling for confounders.
To show that colistin used at a dose >6 million IU per day is associated with improved outcomes in comparison with lower dose, after controlling for confounders.

Condition
Clinically Significant Bacteremia

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Retrospective
Official Title:	Impact of Specific Antimicrobials and Minimal Inhibitory Concentration(MIC) Values on the Outcome of Bloodstream Infections Due to ESBL or Carbapenemase-producing Enterobacteriaceae: an Observational Multinational Study

Further study details as provided by Spanish Network for Research in Infectious Diseases:

Primary Outcome Measures:

Cure rate at day 14 [ Time Frame: within the first 14 days after treatment started ] [ Designated as safety issue: No ]
o Cure: resolution of all signs and symptoms related to the infection, and antibiotic therapy is no longer necessary

Secondary Outcome Measures:

Mortality at 72 hours [ Time Frame: within the first 72 hours ] [ Designated as safety issue: No ]
Dead: death of the patient for whatever the reason.
Mortality at 7 days [ Time Frame: within 7 days after treatment started ] [ Designated as safety issue: No ]
Dead: death of the patient for whatever the reason.
Mortality at 14 days [ Time Frame: within 14 days after treatment started ] [ Designated as safety issue: No ]
Dead: death of the patient for whatever the reason.
Mortality at 30 days [ Time Frame: within 30 days after treatment started ] [ Designated as safety issue: No ]
Dead: death of the patient for whatever the reason.
Clinical Improvement at 72 hours [ Time Frame: within the first 72 hours after treatment started ] [ Designated as safety issue: No ]
Improvement: partial control or resolution of signs and symptoms related to the infection, or resolution but antibiotic therapy is still necessary.

Non-improvement or deterioration: clinical situation qualified as similar or worse in comparison to that at the diagnosis of bacteremia.
Clinical cure at 28 days [ Time Frame: within 28 days after treatment started ] [ Designated as safety issue: No ]
Clinical Cure: resolution of all signs and symptoms related to the infection, and antibiotic therapy is no longer necessary.

Estimated Enrollment:	2000
Study Start Date:	January 2013
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

- Episode of clinically-significant monomicrobial BSI due to ESBL or carbapenemase-producing Enterobacteriaceae, including community and nosocomial ones

Criteria

Inclusion Criteria:

Episode of clinically-significant monomicrobial BSI due to ESBL or carbapenemase-producing Enterobacteriaceae, including community and nosocomial ones.
- For ESBL-producers, detection by standard phenotypic method as recommended by CLSI is enough (although PCR-based characterisation is preferred, see below).
- For carbapenemase-producers, characterisation by at least PCR is necessary (isolates in which carbapenemase production is suspected based on antimicrobial susceptibility profile plus phenotypic tests alone is not acceptable, see below).
Subsequent episodes in a patient caused by the same microorganism may be included if the interval between them is >3 months.
No age limits.

Exclusion Criteria:

Polymicrobial or non-clinically significant episodes. Episodes in which a potential contaminant (e.g., coagulase-negative staphylococci) is isolated only in one set of blood cultures and there is not a typical source of infection for that kind of organism (e.g. catheter-related) may be included.
Unavailability of key data (such cases should be counted to analyse a potential selection bias)
Episode occurring before January 2004.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01764490

Contacts

Contact: BELEN GUTIERREZ, MD		belengutiguti@hotmail.com
Contact: JUAN GALVEZ, MD, PhD		jga@us.es

Locations

Spain
Virgen Macarena University Hospital	Recruiting
Seville, Andalucia, Spain, 41009
Contact: BELEN GUTIERREZ belengutguti@hotmail.com

Sponsors and Collaborators

JESUS RODRIGUEZ BAÑO

Investigators

Study Chair:

JESUS RODRIGUEZ BAÑO, MD, PhD

Spanish Network for Research in Infectious Diseases

More Information

No publications provided

Responsible Party:	JESUS RODRIGUEZ BAÑO, GENERAL COORDINATOR, Spanish Network for Research in Infectious Diseases
ClinicalTrials.gov Identifier:	NCT01764490 History of Changes
Other Study ID Numbers:	REIPI-1WP701, JRB-ANT-2012-01
Study First Received:	December 26, 2012
Last Updated:	February 16, 2013
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Spanish Network for Research in Infectious Diseases:

Bloodstream infections caused by multidrug-resistant Enterobacteriaceae, extended-spectrum β-lactamase-producers, carbapenemase-producing organisms

Additional relevant MeSH terms:

Bacteremia
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome

Inflammation
Pathologic Processes
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013

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