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

NCT ID: NCT05689450

Last Updated: 2024-02-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-12-21
• Study Completion Date: 2024-02-02

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.

Conditions

Febrile Neutropenia (FN)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Data collection: Amikacin concentration

Blood samples for the measurement of the concentration and calculation of the AUC of amikacin are collected 60 min (+/-30 min) and 8 h (+/-1 h) after the beginning of amikacin infusion. The blood collection after the start of the amikacin infusion will be repeated during every subsequent amikacin administration, but max. during 3 consecutive days.

Intervention Type: OTHER

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Osthoff, PD Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Division of Internal Medicine

Locations

University Hospital Basel, Division of Internal Medicine

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

2022-01218; am23Osthoff

Identifier Type: -

Identifier Source: org_study_id