Clinical trial NCT05689450: Probability of Optimal Target Attainment of Amikacin in Patients With Febrile Neutropenia During Treatment for a Hematological Disorder
Official title: Probability of Optimal Target Attainment of Amikacin in Patients With Febrile Neutropenia During Treatment for a Hematological Disorder: a Prospective, Single-centre Study and PKPD-analysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Febrile Neutropenia (FN)
Keywords: Amikacin
Hematological disorder
Aminoglycoside (AG)
Area under the curve (AUC)
Acute kidney injury (AKI)
Pharmacokinetics and pharmacodynamics (PKPD) analysis
Peak serum concentration (Cmax)
Trough serum concentration (Cmin)
Renal toxicity
Pharmacological target attainment
Amikacin concentration
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-01-19
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Inpatients being at risk of developing FN after treatment for a hematological disorder, admitted to the Department of Internal Medicine or the Department of Hematology at the University Hospital Basel (USB) and who are intended to receive amikacin iv during their hospital stay will be screened for eligibility.

Brief summary: The present trial is a single center, prospective, observational pharmacokinetics and pharmacodynamics (PKPD) cohort study investigating whether patients suffering from a hematological disorder and treated with amikacin due to febrile neutropenia (FN) achieve the predefined amikacin target concentration (Cmax ≥60 mg/L).

Detailed description: Amikacin is an aminoglycoside (AG) that exerts a rapid bactericidal effect against many Gram-negative pathogens. Its pharmacological effect depends on the peak concentration achieved. However, a common side effect of AG is dose-dependent acute kidney injury (AKI), especially when administered over several days due to an accumulation of the drug in the proximal renal tubular cells. In patients in advanced stage of a hematological disease, low body weight influences amikacin pharmacokinetics and pharmacodynamics (PKPD) and increases its clearance. However, there is little known about amikacin PKPD in patients with febrile neutropenia (FN). Whereas the therapeutic efficacy is associated with the peak concentration of AG, toxicity of AG depends on the area under the curve (AUC) or trough level of the drug. When using the AUC to predict renal toxicity, an AUC between 200 and 300 mg/L \* h of amikacin has been proposed as a potential threshold for renal toxicity. At the University Hospital Basel (USB), amikacin is administered intravenously (iv) as once daily infusion combined with cefepime or piperacillin/tazobactam immediately after the occurrence of a fever spike in patients with FN. After the iv administration of amikacin, peak concentration is achieved after 30-60 min. The in-house guidelines recommend the administration of lower amikacin dosages compared to other published studies (15 mg/kg body weight vs. 20 mg/kg or up to 30 mg/kg). It remains unclear if adequate peak concentrations are achieved in patients with FN, when lower amikacin doses are administered. The aim of this study is to investigate the probability of optimal pharmacological target attainment (Cmax ≥60 mg/L) during amikacin treatment among patients with FN treated for hematological disorder in order to evaluate the in-house amikacin dosage recommendations. The current project includes the sampling of biological material during hospital admission and the collection of health-related personal data.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Informed consent (IC) as documented by signature
* Documented hematological disorder
* Hospitalization at the USB due to the treatment for a hematological disorder (e.g. chemotherapy, stem cell transplantation)
* Being at risk of developing FN during the hospital stay (e.g. because of chemotherapy)

Exclusion Criteria:

* Previous enrolment into the current study
* Outpatients
* Patients undergoing hemodialysis
* Women who are pregnant (special pharmacokinetic)

Primary outcomes:
measure: Change in pharmacological target attainment (Cmax ≥60 mg/L) in blood during amikacin treatment
timeFrame: 60 minutes (+/-30 minutes) and 8 hours (+/-1 hour) after the beginning of amikacin infusion on day 1, day 2 and day 3
Secondary outcomes:
measure: AUC >200 mg/L and AUC >300 mg/L* h during amikacin treatment
timeFrame: Up to 3 days after the beginning of amikacin infusion
measure: Percentage of patients achieving a calculated Cmin <4 mg/L in blood
timeFrame: Up to 3 days after the beginning of amikacin infusion
measure: Incidence of Acute kidney injury (AKI)
timeFrame: Within 7 days after application of amikacin
measure: Percentage of patients with optimal pharmacological target attainment
timeFrame: Up to 3 days after the beginning of amikacin infusion
measure: Time interval between the detection of the first fever spike and the administration of amikacin
timeFrame: One time assessment at baseline (Day 1)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Internal Medicine
Study officials:
affiliation: University Hospital Basel, Division of Internal Medicine
name: Michael Osthoff, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: