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Optimization of Beta-lactam Dosing in Critically Ill Patients With Cystatin C (OPTIMIZE-GNI)
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
This is a Phase 4, interventional, multi-center pharmacokinetics (PK) study in up to 200 adult patients who are residing in an ICU. This study will compare the abilities of Cystatin C (CysC) and CysC-based estimated Glomerular Filtration Rate (eGFR) equations to characterize the PK profiles of meropenem and cefepime relative to Serum Creatinine (SCR), Serum Creatinine based Equation (SCRE), and iohexol in critically ill patients with suspected or documented AMR Gram-negative infections. We hypothesize that CysC and CysC-based eGFR equations will characterize the PK profiles of meropenem and cefepime at the population and individual levels with greater accuracy and precision than SCR and SCREs. Iohexol will be administered to patients enrolled in the study and serve as the reference indicator of measured Glomerular Filtration Rate (mGFR), which is the gold standard assessment of kidney function. We further hypothesize that the predictive performances of CysC and CysC-based eGFR equations in estimating the PK profiles of meropenem and cefepime at the population and individual levels will be comparable to iohexol. Firstly, population PK (PopPK) modeling will be used to develop meropenem and cefepime PopPK models informed by CysC, CysC-based eGFR equations, SCR, and SCREs (renal function biomarkers), and iohexol clearance. Secondly, model diagnostics will then be used to compare the predictive performances of the renal function biomarkers PopPK models for each antibiotic relative to iohexol PopPK model. Lastly, Monte Carlo simulation (MCS) will be used to design PK/ pharmacodynamics (PD) optimized meropenem and cefepime dosing schemes based on the renal function biomarker PopPK model with the best predictive performance for use in the treatment of critically ill adult patients with suspected or documented AMR Gram-negative infections and varying degrees of renal function. The primary objective of this study is to compare the abilities of renal function biomarkers (CysC, CysC-based eGFR equations, SCR, SCREs) relative to iohexol to characterize the PK profiles of meropenem and cefepime in critically ill adult patients with suspected or documented AMR Gram-negative infections.
Official title: Optimization of Beta-lactam Dosing in Critically Ill Patients With Suspected or Documented Antimicrobial Resistant Gram-Negative Infections With Cystatin-C (OPTIMIZE-GNI)
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
200
Start Date
2025-02-12
Completion Date
2026-10-30
Last Updated
2026-05-29
Healthy Volunteers
No
Conditions
Interventions
Iohexol
Iohexol,N,N´ -Bis(2,3-dihydroxypropyl)-5-\[N-(2,3-dihydroxypropyl)-acetamido\]-2,4,6-triiodoisophthalamide, is a non-ionic, water-soluble radiographic contrast medium with a molecular weight of 821.14 (iodine content 46.36%)
Locations (10)
Harbor UCLA Medical Center - Medicine - Infectious Diseases
Torrance, California, United States
Torrance Memorial Medical Center
Torrance, California, United States
Henry Ford Health System - Henry Ford Hospital
Detroit, Michigan, United States
Corewell Health - Infectious Disease
Royal Oak, Michigan, United States
Duke University Hospital - Infectious Diseases
Durham, North Carolina, United States
East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
Greenville, North Carolina, United States
University of Cincinnati College of Medicine - Division of Infectious Diseases
Cincinnati, Ohio, United States
Oregon Health and Science University - Adult Infectious Diseases Clinic
Portland, Oregon, United States
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, United States
Carilion Roanoke Memorial Hospital
Roanoke, Virginia, United States