Multi-Drug Resistant Organism Network

Completed

• Conditions: Infections Resistant to Multiple Drugs; Bacterial Infections

• Registration Number: NCT03646227
• Lead Sponsor: Duke University

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.

Study Timeline

• Study Start: 2016-06-16
• Study First Submitted: 2018-08-15
• Study First Submitted QC: 2018-08-22
• Study First Posted: 2018-08-24
• Primary Completion: 2020-05-30
• Study Completion: 2020-05-30
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6496

Inclusion Criteria

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

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Source of positive culture	At collection of the MDRO isolates	The differences in outcomes based on the anatomic source of the positive culture are determined. The anatomic sources collected are blood, respiratory, urine, wound, abdominal, and other, which is collected from the medical record.
Length of Stay	Up to 1 year from index culture date	The length of stay is determined by the hospital admission and discharge dates, which is collected from the medical record.
Disposition at Discharge	Up to 1 year from index culture date	The disposition at discharge is a composite of different locations, to which the subject is discharged (skilled nursing facility, home, long term acute care facility, transfer to another hospital, death, or hospice) and it is used to compare patient outcomes based on MDRO collected form the subject.
Charlson Score	At 90 days after discharge from the index hospitalization	Components of the Charlson Score are collected from the medical record and the Charlson comorbidity index is calculated to determine chronically ill subjects.
ICU Admissions	Up to 1 year from index culture date	The total number ICU days during the index hospitalization will be collected from the medical record to determine high risk populations and exposure.
Antibiotic Summary	Only during hospitalization and up to one year from index culture date	All antibiotics administered during the hospital stay will be collected from the medical record. The antibiotic name, duration of therapy, frequency of dosing, dosage, and reason for discontinuation will be collected for the antibiotics of interest.
Pitt Bacteremia Score	On the day of index culture	Components of the Pitt Bacteremia Score are collected from the medical record and the Pitt bacteremia score is calculated to determine acutely ill subjects.
Survival Status	90 days from discharge or up to one year from index hospitalization.	Survival status will be collected through 90 days after discharge from index hospitalization, up to one year, to determine mortality.
Readmission Status	90 days after discharge from index hospitalization.	Readmission data will be collected through 90 days after discharge from index hospitalization to determine readmission.

Trial Locations

Locations (4)

Huashan Hospital; 🇨🇳 Shanghai, Shanghai, China

Universidad El Bosque; 🇨🇴 Bogota, Colombia

Duke Clinical Research Institute; 🇺🇸 Durham, North Carolina, United States

The University of Queensland Centre for Clinical Research; 🇦🇺 Herston, Queensland, Australia