Clinical trial NCT03646227: Multi-Drug Resistant Organism Network
Official title: Multi-Drug Resistant Organism Network - MDRO Network
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infections Resistant to Multiple Drugs
Bacterial Infections
Keywords: Carbapenem-resistant enterobacteriaceae (CRE)
Carbapenem-resistant Pseudomonas aeruginosa (CRPA)
Klebsiella pneumoniae
Acinetobacter baumannii (CRAb)
Bloodstream infection (BSI)
Microbiological characterization
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2018-08-24
Enrollment: 6496
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohorts will be constructed for each MDRO of eligible patients by investigating hospitalized patients who have an MDRO isolated in clinical cultures from any anatomical site. This study will be conducted under a waiver of informed consent to facilitate universal inclusion. All patients who are admitted to one of the participating hospitals and who have an MDRO - as defined in the specific sub-study protocol (Appendices) - isolated in a clinical culture are targeted for inclusion.

Brief summary: This study is specifically designed to provide observational data which can be used to help in the design of future randomized clinical trials on both therapeutics and diagnostics for MDRO infections. To this end, clinical and epidemiological data will be collected on patients who have MDRO isolated from clinical cultures during hospitalization, as well as descriptions of the outcomes of patients treated with various antimicrobial regimens. Molecular and microbiological characterization will also be performed on MDRO isolates. These data will include a detailed clinical and epidemiological description of patients including identifying potential barriers to enrollment in future trials. In addition, data will be collected on species, strain type, and mechanism of drug resistance of the causative organism. Knowing the molecular characteristics will further inform future trial design as not all diagnostics detect and not all therapeutics are active against the same mechanisms of resistance.

Detailed description: This is a prospective multi-center study. At each hospital, study personnel will screen the microbiology laboratory logs to identify all patients found to have a MDRO isolate from one or more anatomical sites during hospitalization. For each patient identified, designated site personnel will access the patient's medical record and use web-based data entry to enter the relevant data into the electronic case report form (eCRF) in the study's centralized database.

A sample of all MDRO isolates (bacterial isolates) will be sent to a central research laboratory for molecular analysis which will include strain typing. In addition, the mechanism of resistance will be determined by performing PCR and/or Whole Genome Sequencing.

Aim 1. Identification of target population and high volume centers. The prevalence of specific MDRO is extremely variable in various patient populations. In addition, over time, prevalence patterns for specific MDRO tend to change. The data collection carried out under this protocol will provide real-time data on which patients are the target population for any trial directed against MDRO infection. Also, the data collected will indicate which geographic areas and which centers have the highest incidence of MDRO infections. This will facilitate rational site selection for future trials.

Aim 2. Provide data on impact of potential inclusion/exclusion criteria on enrollment in future trials.

Detailed clinical data will be collected to guide the future development of clinical trials. The eCRF is designed to collect data on the most common barriers to enrollment in clinical trials. Data can then be used in the design of future trials to be presented to pharmaceutical companies, as well as to regulators from the FDA, to provide a rationale for requesting exceptions in inclusion/exclusion criteria. This will result in clinical trials that are more readily generalizable.

Aim 3. Provide data on expected outcomes of patients with MDRO infections for power and sample size calculations for future trials.

In the MDRO network, detailed outcomes data will be collected. Data will include survival and microbiologic clearance outcomes when available. In addition, anatomical site specific clinical symptomatic outcomes, modeled on FDA guidance documents, will be documented. Data obtained will aid in guiding the design of future clinical trials by providing data needed for power and sample size calculations.

All hospitalized patients, including pediatric patients, who have an MDRO isolated from a clinical culture will be included. Patients who have a positive culture for MDRO that is obtained outside the hospital setting will not be included, to ensure the ability to collect MDRO isolates and sufficient clinical data. Overall enrollment is expected to be 7000.

This study will request a waiver of informed consent, consistent with CFR Title 45 part 46.116(d). The study does not involve direct interaction with human subjects. The medical records of patients admitted to the hospital will be screened and data collected from those records according this protocol. The patients will not be approached to obtain information, no intervention is being tested. MDRO isolates will be obtained from existing standard of care microbial testing.

Eligibility criteria: Inclusion Criteria:

* Hospitalized patients.
* Must have at least one multi-drug resistant organism isolated from a clinical culture while hospitalized.

Exclusion Criteria:

* Patients who do not have a positive culture during hospitalization.
* Patients who's only positive culture was obtained outside of hospital admission.
* Patients who have cystic fibrosis and a CRPa infection.

Primary outcomes:
measure: Disposition at Discharge
timeFrame: Up to 1 year from index culture date
measure: Charlson Score
timeFrame: At 90 days after discharge from the index hospitalization
measure: Pitt Bacteremia Score
timeFrame: On the day of index culture
measure: Source of positive culture
timeFrame: At collection of the MDRO isolates
measure: Length of Stay
timeFrame: Up to 1 year from index culture date
measure: ICU Admissions
timeFrame: Up to 1 year from index culture date
measure: Antibiotic Summary
timeFrame: Only during hospitalization and up to one year from index culture date
measure: Survival Status
timeFrame: 90 days from discharge or up to one year from index hospitalization.
measure: Readmission Status
timeFrame: 90 days after discharge from index hospitalization.
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Herston
country: Australia
facility: The University of Queensland Centre for Clinical Research
state: Queensland
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Bogota
country: Colombia
facility: Universidad El Bosque
Study officials:
affiliation: University of North Carolina
name: David van Duin, MD. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Cleveland Medical Center
name: Robert Bonomo, MD
role: PRINCIPAL_INVESTIGATOR
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