Probability of Optimal Target Attainment of Amikacin in Patients With Febrile Neutropenia During Treatment for a Hematological Disorder

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05689450

Collaborator

(none)

Enrollment

Location

17.3

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Febrile Neutropenia (FN)	Other: Data collection: Amikacin concentration

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

50 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Dec 21, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Outcome Measures

Primary Outcome Measures

Change in pharmacological target attainment (Cmax ≥60 mg/L) in blood during amikacin treatment [60 minutes (+/-30 minutes) and 8 hours (+/-1 hour) after the beginning of amikacin infusion on day 1, day 2 and day 3]
Percentage of patients with optimal pharmacological target attainment (Cmax ≥60 mg/L) in blood during amikacin treatment

Secondary Outcome Measures

AUC >200 mg/L and AUC >300 mg/L* h during amikacin treatment [Up to 3 days after the beginning of amikacin infusion]
Percentage of patients achieving the threshold of potential renal toxicity defined as AUC >200 mg/L and AUC >300 mg/L* h respectively during amikacin treatment
Percentage of patients achieving a calculated Cmin <4 mg/L in blood [Up to 3 days after the beginning of amikacin infusion]
Percentage of patients achieving a calculated Cmin <4 mg/L in blood during amikacin treatment
Incidence of Acute kidney injury (AKI) [Within 7 days after application of amikacin]
Incidence of AKI
Percentage of patients with optimal pharmacological target attainment [Up to 3 days after the beginning of amikacin infusion]
Percentage of patients with optimal pharmacological target attainment using a Cmax/minimal inhibitory concentration (MIC) ≥8 in patients with an identified causative pathogen
Time interval between the detection of the first fever spike and the administration of amikacin [One time assessment at baseline (Day 1)]
Time interval between the detection of the first fever spike and the administration of amikacin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)