Multi-Drug Resistant Organism Network

Bacterial Infections Clinical Trial

— MDRO Network  

Official title:

Multi-Drug Resistant Organism Network - MDRO Network

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03646227
• Other study ID #: Pro00071149
• Secondary ID: UM1AI104681
• Status: Completed
• Start date: June 16, 2016
• Est. completion date: May 30, 2020

Study information

• Verified date: March 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6496
• Est. completion date: May 30, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infections
• Infections Resistant to Multiple Drugs

Intervention

Other:
• Standard of Care
There is no prescribed intervention for this study. Standard of care will be captured in the eCRF.

Locations

Country	Name	City	State
Australia	The University of Queensland Centre for Clinical Research	Herston	Queensland
China	Huashan Hospital	Shanghai	Shanghai
Colombia	Universidad El Bosque	Bogota
United States	Duke Clinical Research Institute	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Australia,  China,  Colombia, 

References & Publications (11)

American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. doi: 10.1164/rccm.200405-644ST. No abstract available. — View Citation

Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug;8(4):R204-12. doi: 10.1186/cc2872. Epub 2004 May 24. — View Citation

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8. — View Citation

Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999 Jan;11(1):7-12. doi: 10.1016/s0924-8579(98)00060-0. — View Citation

Clatworthy AE, Pierson E, Hung DT. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol. 2007 Sep;3(9):541-8. doi: 10.1038/nchembio.2007.24. — View Citation

Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008 Jun;36(5):309-32. doi: 10.1016/j.ajic.2008.03.002. No abstract available. Erratum In: Am J Infect Control. 2008 Nov;36(9):655. — View Citation

Infectious Diseases Society of America (IDSA); Spellberg B, Blaser M, Guidos RJ, Boucher HW, Bradley JS, Eisenstein BI, Gerding D, Lynfield R, Reller LB, Rex J, Schwartz D, Septimus E, Tenover FC, Gilbert DN. Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis. 2011 May;52 Suppl 5(Suppl 5):S397-428. doi: 10.1093/cid/cir153. No abstract available. — View Citation

Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available. — View Citation

van Duin D, Perez F, Rudin SD, Cober E, Hanrahan J, Ziegler J, Webber R, Fox J, Mason P, Richter SS, Cline M, Hall GS, Kaye KS, Jacobs MR, Kalayjian RC, Salata RA, Segre JA, Conlan S, Evans S, Fowler VG Jr, Bonomo RA. Surveillance of carbapenem-resistant Klebsiella pneumoniae: tracking molecular epidemiology and outcomes through a regional network. Antimicrob Agents Chemother. 2014 Jul;58(7):4035-41. doi: 10.1128/AAC.02636-14. Epub 2014 May 5. — View Citation

Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug? J Infect. 2013 May;66(5):401-14. doi: 10.1016/j.jinf.2012.10.028. Epub 2012 Nov 6. — View Citation

Zasowski EJ, Rybak JM, Rybak MJ. The beta-Lactams Strike Back: Ceftazidime-Avibactam. Pharmacotherapy. 2015 Aug;35(8):755-70. doi: 10.1002/phar.1622. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disposition at Discharge	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.	Up to 1 year from index culture date
Primary	Charlson Score	Components of the Charlson Score are collected from the medical record and the Charlson comorbidity index is calculated to determine chronically ill subjects.	At 90 days after discharge from the index hospitalization
Primary	Pitt Bacteremia Score	Components of the Pitt Bacteremia Score are collected from the medical record and the Pitt bacteremia score is calculated to determine acutely ill subjects.	On the day of index culture
Primary	Source of positive culture	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.	At collection of the MDRO isolates
Primary	Length of Stay	The length of stay is determined by the hospital admission and discharge dates, which is collected from the medical record.	Up to 1 year from index culture date
Primary	ICU Admissions	The total number ICU days during the index hospitalization will be collected from the medical record to determine high risk populations and exposure.	Up to 1 year from index culture date
Primary	Antibiotic Summary	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.	Only during hospitalization and up to one year from index culture date
Primary	Survival Status	Survival status will be collected through 90 days after discharge from index hospitalization, up to one year, to determine mortality.	90 days from discharge or up to one year from index hospitalization.
Primary	Readmission Status	Readmission data will be collected through 90 days after discharge from index hospitalization to determine readmission.	90 days after discharge from index hospitalization.

External Links

•   Antibacterial Resistance Leadership Group (ARLG)