Clinical trial NCT03714789: Clearance and Pharmacokinetics of Antibiotics in Renal Replacement Therapy
Official title: Clearance and Pharmacokinetics of Antibiotics With Different Protein-bound Levels in Renal Replacement Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Failure
Keywords: Kidney Failure
Pharmacokinetics
Antibiotics
Lead sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Sponsor class: OTHER
Collaborators: name: Institute of Antibiotics, Huashan Hospital, Fudan University
First posted: 2018-10-22
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients aged from 18 to 85 years, requiring dialysis including intermittent hemodialysis(IHD) or hemodiafiltration(HDF), and receiving meropenem, vancomycin or ceftriaxone based on clinical grounds from a university-affiliated hospital in Shanghai, China.

Brief summary: This is an observational study that evaluates the dialysis clearance and pharmacokinetics of antibiotics with different protein-bound levels in patients receiving renal replacement therapy. Meropenem, vancomycin and ceftriaxone are selected to represent three typical protein-bound levels, and the primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). During and after the dialysis, the drug levels in both plasma and spent dialysate are monitored, but no changes are made to therapy. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

Detailed description: This prospective, single-center observational study is taken to evaluate the dialysis clearance and pharmacokinetics of antibiotics with three different protein-bound levels in patients receiving renal replacement therapy. As is known that the plasma protein binding rate affects the distribution, metabolism and elimination of the drug in the body, and is also an important factor affecting the removal during dialysis, the study selects meropenem, vancomycin and ceftriaxone, of which the protein-bound levels are respectively 2%, 55% and 85%, to represent three typical protein-bound levels. The primary dialysis methods being studied are intermittent hemodialysis(IHD) and hemodiafiltration(HDF). The dialysis pattern, the antibiotic choice and its dosage for each subject are made on clinical grounds. A total of 16 milliliters of blood and 60 milliliters of spent dialysate are collected from each subject for each dialysis pattern. The study will provide detailed information on the characteristics of the removal kinetics of the three antibiotics during dialysis, and evaluate whether the dosing regimens are the most appropriate to achieve therapeutic targets while minimizing the risk of toxicity.

Eligibility criteria: Inclusion Criteria:

* With Age from 18 to 85 years old.
* With weight from 50 to 75 kilograms.
* Requiring dialysis including intermittent hemodialysis(IHD) or hemodiafiltration(HDF).
* Receiving meropenem, vancomycin or ceftriaxone based on clinical grounds.

Exclusion Criteria:

* Patient is during pregnant or lactation period.
* Patient is allergic to meropenem, vancomycin or ceftriaxone.
* Severe hypoproteinemia (serum total protein\<=45g/L) or severe hypoalbuminemia（serum albumin\<20g/L).
* Severe liver dysfunction（ALT\>200U/L or AST\>200U/L).
* The patient himself or his immediate family refuses to sign the informed consent.

Primary outcomes:
measure: Dialytic clearance (K_total)
timeFrame: During the session of dialysis, up to 4 hours
measure: Area under the concentration-time curve (AUC)
timeFrame: During the session of dialysis, up to 4 hours
Secondary outcomes:
measure: Rebound of plasma concentration (Rebound_1h%)
timeFrame: At the end of dialysis and an hour after dialysis
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital
Study officials:
affiliation: Division of Nephrology,Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University
name: Feng Ding, PhD
role: STUDY_DIRECTOR
References: