Clinical trial NCT04758442: Optimal Dosing of Vancomycin in an Adult Population of Hemato-oncology
Official title: Optimal Dosing of Vancomycin in an Adult Population of Hemato-oncology: a Nomogram Based on a Bayesian Population Model to Predict Initial Dosage of Vancomycin
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vancomycin
Hematologic Malignancies
Febrile Neutropenia
Keywords: Bayesian model
Pharmacokinetics
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2021-02-17
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a single-center prospective pharmacokinetic study. The principal objective is to collect new data among patients with hematologic cancer to develop a Bayesian population pharmacokinetic model and to improve dose adjustment of intravenous vancomycin. Approximately 40 subjects meeting the inclusion and no exclusion criteria will be enrolled in the study. Vancomycin blood concentration will be measured at steady-state at three different moment for each participant : immediately before the infusion, 1 hour after the infusion and during the elimination phase (at 3, 4 or 5 hours after the infusion). This additional vancomycin serum concentration in the elimination phase will be used to estimate more precisely the vancomycin pharmacokinetic parameters in this specific population including the distribution volume and the elimination of the molecule. Ultimately, the purpose of this study is to create a nomogram to predict the optimal initial vancomycin dosing in adult patients with a hematologic cancer.

Detailed description: STUDY DESIGN:

Prospective, monocentric, pharmacokinetic study.

Adults who have been diagnosed with a hematologic malignancy, are hospitalized at Maisonneuve-Rosemont hospital and received at least 3 doses of intravenous vancomycin.

Pharmacokinetic parameters: Serum vancomycin concentration measured at steady state just before the beginning of the infusion (trough), 1 hour after completion of the infusion (peak) and between 3 to 5 hours after the end of the infusion (additional blood draw during the elimination phase).

RECRUITMENT PROCESS:

A systematic daily screening of hospitalized patients diagnosed with a hematologic cancer will be made by the research team and the pharmacists 7 days a week. An information sheet will be given to all potential eligible patients at their admission. When intravenous vancomycin is prescribed, a member of the research team will explain the study and present the Information and Consent Form (ICF) to the potential participant to obtain his/her official informed consent.

DATA COLLECTION:

Three blood draws will be planned around the fourth or fifth dose of vancomycin and collected by the nursing team. The sampling scheme is as follows: just before the beginning of the infusion (trough), 1 hour after completion of the infusion (peak) and 3, 4 or 5 hours after the end of the infusion (additional blood draw during the elimination phase) according to the assigned time of the participant. The assigned time of the additional blood draw will be randomized at the inclusion of the subject in the study. A member of the research team will provide the tubes to the nurse, will write and save sampling times and will ship the blood samples to the laboratory.

Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 and over;
* Subjects diagnosed with a hematologic cancer;
* Subjects hospitalized at Maisonneuve-Rosemont hospital between February 2021 and August 2021;
* Intravenous vancomycin treatment prescribed by a doctor;
* Subjects received at least 3 doses of intravenous vancomycin.

Exclusion Criteria:

* Non-malignant diagnosis (aplastic anemia and rare metabolic diseases);
* Subjects admitted to a critical care unit;
* End-stage renal disease (GFR \< 15 mL/min/1.73m2);
* Patients undergoing dialysis/renal replacement therapy;
* Acute kidney injury at the moment of the first vancomycin dosage (definition adapted from KDIGO criteria):

  1. Increase in serum creatinine by ≥ 26.5 umol/L within 48 hours or
  2. Increase in serum creatinine to ≥ 1.5 times baseline within prior 7 days
* Pregnant women;
* Severely burn patients;
* Inability to give free and informed consent.

Primary outcomes:
measure: Pharmacokinetic Parameters : Volume of Distribution
timeFrame: During intravenous vancomycin treatment assessed to 72 hours
measure: Pharmacokinetic Parameters : Vancomycin clearance
timeFrame: During intravenous vancomycin treatment assessed to 72 hours
Secondary outcomes:
measure: Area Under the concentration-time Curve (AUC)
timeFrame: between 0 to 24 hours during vancomycin administration
measure: Serum Vancomycin Through Concentration
timeFrame: 5 minutes before the selected infusion
measure: Serum Vancomycin Peak Concentration
timeFrame: 60 minutes after the end of the infusion
measure: Serum Vancomycin Elimination Phase Concentration
timeFrame: 3 to 5 hours after the end of the infusion (+/- 30 minutes)
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
Study officials:
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