Optimizing Clinical Use of Polymyxin B

NCT02682355 | Completed

• 1 other identifier: R01AI119446-01
• Study Type: observational
• Target: 155
• Locations: 3 countries
• Sites: 6

Brief Summary

Polymyxin B is already being used extensively in the USA and other parts of the world; its use is likely to rapidly increase due to the greater burden of infections caused by MDR Gram-negative bacteria and the growing awareness of the limitations inherent in the clinical pharmacology of CMS/colistin. Cross resistance exists between the two polymyxins and thus both must be dosed optimally; but the recently generated scientifically-based dosage regimens for CMS/colistin cannot be extrapolated to polymyxin B. It is essential that an adequately powered study is conducted to define the clinical PK/PD/TD relationships of polymyxin B and identify, using next-generation proteomics, biomarkers for early detection of kidney injury. This will allow the development of scientifically-based dosage regimens for various categories of patients and an adaptive feedback control clinical tool for optimized dosing of polymyxin B in future individual patients.

Conditions

Pneumonia; Blood Stream Infection; Urinary Tract Infections; Respiratory Tract Infection (Including Tracheobronchitis); Sepsis

Outcome Measures

Primary Outcomes (1)

• Polymyxin B plasma concentrations

  28 days after enrollment

Secondary Outcomes (3)

• Changes in serum creatinine

  28 days after enrollment

• Clinical response based on resolution of signs and symptoms of infection

  28 days after enrollment

• Microbiologic response based on eradication of pathogens from blood and respiratory cultures

  28 days after enrollment

Study Arms (1)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The human subjects involved in this study will be receiving intravenous polymyxin B as part of their routine clinical care because of infection due to bacteria resistant to all other first-line antibiotics.

You may qualify if:

• Patient of 18 years of age or older
• Expectation of hospitalization and receipt of polymyxin B of ≥ 48 hours
• Receipt of intravenous polymyxin B for treatment of bacteremia and/or urinary tract infection and/or respiratory tract infection (including tracheobronchitis) or sepsis
• Provision of written informed consent by the patient or by the patient's health care proxy if the patient cannot give consent
• Adequate venous access to enable collection of blood for determination of concentrations of polymyxin B and co-administered antibiotics

You may not qualify if:

• Age \<18 years
• Currently incarcerated
• Concomitant use of polymyxin B delivered directly into the respiratory tract
• Cystic fibrosis
• Known allergy to CMS/colistin or polymyxin B
• Anticipated death within 48 h of commencing polymyxin B therapy

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead

Study Sites (6)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

New York Presbyterian-Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Hospital Sao Lucas da - PUC / RS

Porto Alegre, 10032, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, 90035-001, Brazil

Location

Singapore General Hospital

Singapore, 16908, Singapore

Location

Biospecimen

Retention: SAMPLES WITH DNA

* Blood and Respiratory cultures from infection site. * Urine Samples for Proteomic testing. * Blood Specimen for Pharmacokinetic/Pharmacodynamic testing.

MeSH Terms

Conditions

Pneumonia; Urinary Tract Infections; Respiratory Tract Infections; Sepsis

Condition Hierarchy (Ancestors)

Infections; Lung Diseases; Respiratory Tract Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Keith S Kaye, MD, MPH

  Rutgers University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Director, Principal Investigator

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: February 15, 2016
• Study Start: February 1, 2016
• Primary Completion: May 31, 2022
• Study Completion: August 3, 2022
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

US (3); SG (1); BR (2)