Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
155 participants
OBSERVATIONAL
2016-02-29
2022-08-03
Brief Summary
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Detailed Description
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The Specific Aims are:
1. To develop a population PK model for polymyxin B;
2. To investigate relationships between the PK of polymyxin B, duration of therapy and patient characteristics, with the development and timing of nephrotoxicity; and to use next-generation proteomics to identify the most predictive biomarker(s) of polymyxin B associated nephrotoxicity; and to develop the population PK/TD model;
3. To establish the relationships between polymyxin B PK, bacterial susceptibility and patient characteristics, with the probability of attaining and time to achieving clinical and bacteriological outcomes; and
4. To employ the models from Aims 1-3 and Monte Carlo simulation to develop scientifically-based dosage regimens of polymyxin B and to develop an AFC algorithm for future individual patients.
Research Design: Patients being treated with intravenous polymyxin B will be identified at three clinical sites in the USA and one in Singapore. Patients (n = 250) will have blood collected at various times surrounding a dose of polymyxin B between days 1 and 5 of therapy. Development of nephrotoxicity, clinical response, and bacteriological response will be examined. Total and free plasma concentrations of polymyxin B will be determined. Bacterial isolates will be examined for the emergence of polymyxin resistance. The relationships between polymyxin B PK, PD and TD end-points (e.g. clinical and bacteriological responses, development of toxicity and resistance) will be assessed using pharmacometric analyses. Finally, the obtained information will be used to apply Monte Carlo simulation to examine the impact of various patient characteristics and other factors on polymyxin B PK, PD and TD, in order to establish optimal dosage regimens and AFC algorithms for individual critically-ill patients.
Significance: No new antibiotics will be available for Gram-negative 'superbugs' for many years. This landmark multicenter study will provide essential information for optimizing polymyxin B use in critically-ill patients, while minimizing resistance and toxicity. This proposal aligns perfectly with the NIAID priority "To teach old drugs new tricks" and the recent Executive Order of the White House to combat antibiotic resistance.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Study cohort
Patients receiving IV polymyxin B for treatment of bacteremia and/or urinary tract infection and/or respiratory tract infection (including tracheobronchitis) or sepsis
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
2. Expectation of hospitalization and receipt of polymyxin B of ≥ 48 hours
3. Receipt of intravenous polymyxin B for treatment of bacteremia and/or urinary tract infection and/or respiratory tract infection (including tracheobronchitis) or sepsis
4. Provision of written informed consent by the patient or by the patient's health care proxy if the patient cannot give consent
5. Adequate venous access to enable collection of blood for determination of concentrations of polymyxin B and co-administered antibiotics
Exclusion Criteria
2. Currently incarcerated
3. Concomitant use of polymyxin B delivered directly into the respiratory tract
4. Cystic fibrosis
5. Known allergy to CMS/colistin or polymyxin B
6. Anticipated death within 48 h of commencing polymyxin B therapy
18 Years
ALL
No
Sponsors
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Rutgers, The State University of New Jersey
OTHER
Responsible Party
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Keith S. Kaye, MD, MPH
Project Director, Principal Investigator
Principal Investigators
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Keith S Kaye, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
Rutgers University
Locations
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Northwestern University
Chicago, Illinois, United States
Columbia University Medical Center
New York, New York, United States
New York Presbyterian-Weill Cornell Medical Center
New York, New York, United States
Hospital Sao Lucas da - PUC / RS
Porto Alegre, , Brazil
Hospital Moinhos de Vento
Porto Alegre, , Brazil
Singapore General Hospital
Singapore, , Singapore
Countries
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Provided Documents
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Document Type: Informed Consent Form
Other Identifiers
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