Actively Recruiting
Optimization of Beta-lactam Dosing in Critically Ill Patients With Cystatin C (OPTIMIZE-GNI)
Led by National Institute of Allergy and Infectious Diseases (NIAID) · Updated on 2026-05-11
200
Participants Needed
10
Research Sites
89 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Optimization of Beta-lactam Dosing in Critically Ill Patients With Cystatin C (OPTIMIZE-GNI)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at enrollment
- Currently residing in an intensive care unit (ICU)
- Suspected or confirmed antimicrobial resistant Gram-negative infection treated with meropenem or cefepime
- Expected to remain in ICU and receive meropenem or cefepime for the study duration
- Sufficient intravenous or arterial access for drug infusion and blood sampling
- Ability to provide informed consent or have a legally authorized representative consent
You will not qualify if you...
- Known allergy or hypersensitivity to iohexol, any contrast agents, or iodine
- Prior severe skin reactions to iohexol, contrast agents, or iodine
- Received iohexol on the day of enrollment or expected to receive it as standard care during the study
- Major surgery within one day before enrollment
- Recent burn involving over 25% of total body surface area within 6 months
- Penetrating injury within one day before enrollment
- Currently receiving or expected to receive renal replacement therapies such as hemodialysis or ECMO during the study
- Diagnosed diabetes with serum creatinine over 3 mg/dL during screening
- Severe thyrotoxicosis documented during screening
- Homozygous sickle cell disease
- Diagnosed hepatorenal syndrome
- Anuria (urine output less than 100 mL per day) for one or more days during screening with certain medical conditions
- Pregnant or breastfeeding
- Received or expected to receive albumin from one day before enrollment through study end
- Received or expected to receive 3 or more units of blood products (excluding platelets) from one day before enrollment through study end
- Any condition that the investigator judges would affect participant safety or study participation
AI-Screening
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Trial Site Locations
Total: 10 locations
1
Harbor UCLA Medical Center - Medicine - Infectious Diseases
Torrance, California, United States, 90502-2006
Actively Recruiting
2
Torrance Memorial Medical Center
Torrance, California, United States, 90505
Actively Recruiting
3
Henry Ford Health System - Henry Ford Hospital
Detroit, Michigan, United States, 48202-2608
Actively Recruiting
4
Corewell Health - Infectious Disease
Royal Oak, Michigan, United States, 48073
Actively Recruiting
5
Duke University Hospital - Infectious Diseases
Durham, North Carolina, United States, 27710
Actively Recruiting
6
East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
Greenville, North Carolina, United States, 27834-9997
Actively Recruiting
7
University of Cincinnati College of Medicine - Division of Infectious Diseases
Cincinnati, Ohio, United States, 45267
Actively Recruiting
8
Oregon Health and Science University - Adult Infectious Diseases Clinic
Portland, Oregon, United States, 97239-3098
Actively Recruiting
9
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, United States, 15213-3403
Actively Recruiting
10
Carilion Roanoke Memorial Hospital
Roanoke, Virginia, United States, 24014
Actively Recruiting
Research Team
T
Thomas Lodise
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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