Pharmacokinetics of Antibiotics in Patients Undergoing Renal Replacement Therapies

Renal Replacement Therapy Clinical Trial

— RRTdose  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03636464
• Other study ID #: A-2017-010
• Status: Recruiting
• Start date: April 1, 2018
• Est. completion date: July 1, 2026

Study information

• Verified date: February 2023
• Source: Cleveland Clinic Abu Dhabi
• Contact: Wasim El Nekidy, PharmD
• Phone: +971 2 6590200
• Email: ElnekiW[@]ClevelandClinicAbuDhabi.ae
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Renal Replacement Therapy

Intervention

Other:
• Blood collection
Pharmacokinetics

Locations

Country	Name	City	State
United Arab Emirates	Cleveland Clinic Abu Dhabi	Abu Dhabi

Sponsors (2)

Lead Sponsor	Collaborator
Cleveland Clinic Abu Dhabi	University of the Sciences in Philadelphia

Country where clinical trial is conducted

United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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