Pharmacokinetics of Antibiotics in Patients Undergoing Renal Replacement Therapies (RRTdose)

Pharmacokinetics and Deposition of Commonly Prescribed Antibiotics in Hospitalized Critically Ill Patients Undergoing Renal Replacement Therapies

The study is aiming to describe the pharmacokinetic and pharmacodynamic profile of intravenous meropenem, ertapenem, cefepime, colistin, Ceftazidime/Avibactam , Ceftolozane/Tazobactam , and piperacillin/tazobactam in the plasma and determine how much is removed by Renal Replacement Therapies to ensure adequate dosing

Study Overview

• Status: Recruiting
• Conditions: Renal Replacement Therapy
• Intervention / Treatment: Other: Blood collection

Detailed Description

This pharmacokinetic evaluation and clinical outcomes will be an open-label study of 12-16 adult patients/antibiotic dose/modality to a total number of 180-240 patients, admitted to the acute care levels or intensive care unit at Cleveland Clinic Abu Dhabi receiving RRT and prescribed these seven antibiotics as recommended by their treating physicians. The collection of blood, ultrafiltrate or effluent fluids depending on RRT modality (HD or CRRT), and urine samples will begin after participants are administered first dose to determine if a loading dose will be required then after at least three doses (as prescribed by the treating physician) once these drugs will be at steady-state concentration. The study intervention duration will depend on dialysis modality expected to be 3 to 5 days depending on RRT modality and patients will be followed for outcomes (death or cure). Collected blood, effluent and urine samples will be assayed for drug concentration. The concentration data will be modeled by a computer program to determine the pharmacokinetic parameters used to predict future dosing in the case of RRT. Linear/logistic regression will be used as a component of statistical analysis to model the relationship between CRRT machine settings and the amount of the study drugs that will be removed by the filter. Information related to adverse events , clinical and microbiological cure will be collected in case report forms.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Wasim El Nekidy, PharmD; Phone Number: 47969 +971 2 6590200; Email: ElnekiW@ClevelandClinicAbuDhabi.ae
• Study Contact Backup: Name: Islam Ghazi, PharmD; Phone Number: +12152688908; Email: i.ghazi@usciences.edu

Study Locations

• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • Recruiting
    • Cleveland Clinic Abu Dhabi
    • Contact: Wasim S El Nekidy, PharmD; Phone Number: 47969 +97125092000; Email: elnekiw@ccaduae.ae
    • Principal Investigator: Wasim El Nekidy, PharmD
    • Principal Investigator: Islam Ghazi, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients on renal replacement therapy, prescribed antibiotics in the regular course of care

Description

Inclusion Criteria:

• Adults > 18 year old
• Prescribed meropenem, ertapenem, cefepime, colistin, Ceftazidime/Avibactam , Ceftolozane/Tazobactam , or piperacillin/tazobactam for treatment of infection as part of standard medical care
• Administered meropenem, ertapenem, cefepime, colistin, Ceftazidime/Avibactam , Ceftolozane/Tazobactam ,or piperacillin/tazobactam while on renal replacement therapy (IHD or CRRT) or renal replacement therapy started while on any of these antibiotics
• Patients with hemoglobin > 70 g/L without blood transfusion in the past 24 hours
• Informed consent given by patient, next of kin or legally authorized representative

Exclusion Criteria:

• Less than 18 years of age
• Pregnant females
• Body mass index < 18 or > 35 kg/m2
• Presence of anemia (defined as hemoglobin < 70 g/L), thrombocytopenia, or leukopenia as defined by hematocrit, platelet, or white blood cell count < 75% of the lower limit of normal
• Concomitant receipt of another cephalosporin interfering with assay
• Participants likely to require surgical interventions during the study period if the surgery would interfere with dosing intervals or affect sampling process
• Protected patients; prisoners, patients with HIV, patients with physical or mental disabilities, psychiatric patients.
• Patients with documented life-threatening allergy (i.e anaphylaxis, angioedema) to any of the study drugs or their class.
• Patients with conditions known to significantly affect PK; (i.e. severe burn, significant ascites, spinal cord injury and cystic fibrosis)
• Any other reason felt by the investigators to potentially affect the outcomes of the study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum antibiotic concentrations over time during dose interval	Blood will be collected at designated time points, serum samples will be assayed for drug concentration over time to describe pharmacokinetic disposition	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of antibiotic removed by dialysis	Dialysate will be collected and assayed for drug concentration to determine the amount of drug cleared by RRT with respect to different dialysis modalities and membranes	24 months
Time above minimum inhibitory concentration (T/MIC) for time dependent antibiotics	Concentration/time data will be modeled mathematically (population pharmacokinetics and Monte Carlo simulation) to identify adequate dosing in this patient population	24 months
Area under concentration time curve over minimum inhibitory concentration for (Cmax/MIC) for concentration dependent antibiotics	Concentration/time data will be modeled mathematically (population pharmacokinetics and Monte Carlo simulation) to identify adequate dosing in this patient population	24 months

Collaborators and Investigators

• Sponsor: Cleveland Clinic Abu Dhabi
• Collaborators: University of the Sciences in Philadelphia
• Investigators: Principal Investigator: Wasim El Nekidy, PharmD, Cleveland Clinic Abu Dhabi; Principal Investigator: Islam Ghazi, PharmD, University of the Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2018
• Primary Completion (ANTICIPATED): July 1, 2025
• Study Completion (ANTICIPATED): July 1, 2026

Study Registration Dates

• First Submitted: July 29, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (ACTUAL): August 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; antibiotics; RRT
• Other Study ID Numbers: A-2017-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No