Association of Cefepime Trough Levels With Clinical Efficacy and Neurotoxicity in Patients With Febrile Neutropenia

NCT04250038 | Unknown

• 1 other identifier: S62297
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

In this prospective monocenter observational study, the objective was to determine a safe and effective therapeutic window for cefepime in patients with neutropenic fever.

Conditions

Pharmacokinetics; Pharmacodynamics; Cefepime

Keywords

Cefepime; Pharmacokinetic; Neurotoxicity; Febrile neutropenia; Exposure

Outcome Measures

Primary Outcomes (3)

• Therapeutic failure

  hemoculture positive for Gram negative bacteria during cefepime therapy

  From Day 2 before until Day 2 day after day of sampling

• Neurotoxicity: cognitive disturbance, confusion, depressed level of consciousness, encephalopathy, hallucinations, movements involuntary, seizure

  Percent of patients and trough levels associated with one of following symptoms during cefepime therapy: cognitive disturbance, confusion, depressed level of consciousness, encephalopathy, hallucinations, movements involuntary, seizure

  From Day 2 before until Day 2 day after day of sampling

• Carryover cefepime in samples via central venous catheter

  Difference between cefepime concentration in samples obtained via central venous catheter vs. samples obtained via peripheral venipuncture

  From Day 2 before until Day 2 day after day of sampling

Secondary Outcomes (2)

• Fever

  From Day 2 before until Day 2 day after day of sampling

• Clinical condition

  From Day 2 before until Day 2 day after day of sampling

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Hemato-oncology patients treated with cefepime for neutropenic fever

You may qualify if:

• admitted to the hemato-oncology ward
• treated with cefepime for neutropenic fever
• written informed consent

You may not qualify if:

• \- younger than 18 years old

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (7)

• Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14.

  PMID: 24429437 BACKGROUND

• Rhodes NJ, Kuti JL, Nicolau DP, Van Wart S, Nicasio AM, Liu J, Lee BJ, Neely MN, Scheetz MH. Defining Clinical Exposures of Cefepime for Gram-Negative Bloodstream Infections That Are Associated with Improved Survival. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1401-10. doi: 10.1128/AAC.01956-15.

  PMID: 26666929 BACKGROUND

• Aitken SL, Altshuler J, Guervil DJ, Hirsch EB, Ostrosky-Zeichner LL, Ericsson CD, Tam VH. Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia. Int J Antimicrob Agents. 2015 May;45(5):541-4. doi: 10.1016/j.ijantimicag.2014.12.018. Epub 2015 Jan 19.

  PMID: 25665726 BACKGROUND

• Lamoth F, Buclin T, Pascual A, Vora S, Bolay S, Decosterd LA, Calandra T, Marchetti O. High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function. Antimicrob Agents Chemother. 2010 Oct;54(10):4360-7. doi: 10.1128/AAC.01595-08. Epub 2010 Jul 12.

  PMID: 20625153 BACKGROUND

• Rhodes NJ, Kuti JL, Nicolau DP, Neely MN, Nicasio AM, Scheetz MH. An exploratory analysis of the ability of a cefepime trough concentration greater than 22 mg/L to predict neurotoxicity. J Infect Chemother. 2016 Feb;22(2):78-83. doi: 10.1016/j.jiac.2015.10.009. Epub 2015 Dec 17.

  PMID: 26712584 BACKGROUND

• Huwyler T, Lenggenhager L, Abbas M, Ing Lorenzini K, Hughes S, Huttner B, Karmime A, Uckay I, von Dach E, Lescuyer P, Harbarth S, Huttner A. Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study. Clin Microbiol Infect. 2017 Jul;23(7):454-459. doi: 10.1016/j.cmi.2017.01.005. Epub 2017 Jan 19.

  PMID: 28111294 BACKGROUND

• Marsh E, Verhoven SM, Groszek JJ, Fissell WH, An G, Patel P, Creech B, Shotwell M. Beta-lactam carryover in arterial and central venous catheters is negligible. Clin Chim Acta. 2018 Nov;486:265-268. doi: 10.1016/j.cca.2018.08.008. Epub 2018 Aug 15.

  PMID: 30118674 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum

MeSH Terms

Conditions

Neurotoxicity Syndromes; Febrile Neutropenia

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Study Officials

• Isabel Spriet, PharmD PhD

  UZ Leuven

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: January 31, 2020
• Study Start: August 1, 2019
• Primary Completion: October 1, 2020
• Study Completion: May 1, 2021
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

BE (1)