Use of a Loading Dose of Vancomycin in Pediatric Dosing

May 22, 2018 updated by: Alicia Demirjian, Boston Children's Hospital

The Use of a Loading Dose of Intravenous Vancomycin Will Achieve Therapeutic Concentration Earlier Than Conventional Pediatric Dosing: A Randomized Controlled Trial

Vancomycin is an antibiotic administered to children or adults for many types of infections. While it has been used to treat infections of children for more than 50 years we are still not completely certain about the best dose to use when starting treatment with this medication.

This study is intended to evaluate whether giving a new higher dose of vancomycin for the first dose will help us get to the desired amount in the body more quickly then the usual first dose. Half of the patients would get the new higher dose and the other half of patients will get the typical first dose. Only the first dose is changed and all doses that follow are the same in both groups and are doses typically used for children.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Setting and Patients We conducted a double-blind randomized controlled trial of children aged 2 to 18 years hospitalized at Boston Children's Hospital between February 1, 2011, and January 15, 2012, who required antimicrobial therapy with vancomycin (Hospira, Inc., Lake Forest, IL, lot #896188EO-4) for a suspected or documented infection. We excluded patients with a body weight above 67 kg (to limit the maximum loading dose to 2 g), preexisting severe renal dysfunction, defined as creatinine clearance <50 mL/min/1.73m2 using the original Schwartz equation,7 known hearing impairment, intravenous vancomycin treatment in the prior 7 days or undergoing a procedure with anticipated moderate to severe blood loss (eg, cardiac surgery or extensive orthopedic procedure).

For all participants enrolled in the study, relevant baseline demographic, medical history and safety data were recorded. Medical history data included primary and secondary diagnoses; other comorbidities such as obesity or cystic fibrosis; and presence of systemic inflammatory response syndrome, defined as 2 or more of the following: temperature >38.5°C or <36°C; mean heart rate >2 standard deviations above normal for age; mean respiratory rate >2 standard deviations above normal for age; or high or low white blood cell count for age.

Randomization and Concealment Participants were randomized in blocks of 2 and 4 to receive either a loading dose of 30 mg/kg of vancomycin as a single intravenous infusion over 2 hours (intervention group) or an initial vancomycin dose of 20 mg/kg intravenously over 2 hours (comparison group). The initial dose was administered over 2 hours in both groups to preserve allocation concealment. All patients subsequently received a 20 mg/kg dose every 8 hours as was the standard of care in our hospital for treatment of severe infections at the time of the study. Subsequent doses were administered over 1 hour, unless the patient developed red man syndrome (as identified by the clinical team), in which case the infusion time was increased to 2 hours. The investigators, family and primary care teams were blinded to group assignment, and the first dose of vancomycin for all participants was prepared so that the solution volumes were identical. The computer-generated randomization was concealed in a locked binder until the intervention was assigned.

Vancomycin Concentration Sampling and Analysis Trough serum vancomycin concentrations were obtained within 60 minutes before the second (8-hour) and third (16-hour) vancomycin doses. In order to increase the likelihood of having a cloud of sparse data for population pharmacokinetic analysis, 1 or 2 additional serum vancomycin samples were obtained from each participant within the first 32 hours of therapy at a time coinciding with blood collection for clinical care. These samples were obtained only from participants with an indwelling catheter whose family provided written consent for additional sampling.

Vancomycin concentrations were measured using a fluorescence polarization immunoassay (Roche Diagnostics, Indianapolis, IN) on the Roche Integra 800 instrument. The assay had a limit of quantitation of 0.74 mg/L and an interassay coefficient of variability of <3%.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Receiving care at Children's Hospital Boston
  • Prescribed intravenous vancomycin by their physician

Exclusion Criteria:

  • Weight above 67 kg
  • Pre-existing renal dysfunction (creatinine clearance < 50 ml/min/1.73m2)
  • Known hearing impairment
  • Recent intravenous vancomycin treatment (within 7 days)
  • Undergoing procedure with anticipated moderate-severe blood loss

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vancomycin loading dose
Intervention: administer intravenous vancomycin 30 mg/kg/dose once, followed 8 hours later by 20 mg/kg/dose every 8 hours
Drug: vancomycin hydrocloride
see description of study arms
Other Names:
  • Vancomycin
Active Comparator: Control
No intervention. Administer intravenous vancomycin 20 mg/kg/dose every 8 hours as per hospital guideline.
Drug: vancomycin hydrocloride
see description of study arms
Other Names:
  • Vancomycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Count of Participants With Vancomycin Trough Between 15 and 20
Time Frame: 8 hours after the first dose of vancomycin
proportion of participants whose vancomycin trough was between 15 and 20 mcg/mL, 8 hours after the first vancomycin dose, in loading dose group as compared to control group
8 hours after the first dose of vancomycin

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AUC/MIC for Vancomycin in the Study Population
Time Frame: within 48 hours after receiving the first dose of vancomycin
AUC/MIC using hypothetical MIC = 1 mg/L
within 48 hours after receiving the first dose of vancomycin

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Investigators

  • Principal Investigator: Alicia A Demirjian, MD, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

January 28, 2011

First Submitted That Met QC Criteria

February 3, 2011

First Posted (Estimate)

February 4, 2011

Study Record Updates

Last Update Posted (Actual)

June 19, 2018

Last Update Submitted That Met QC Criteria

May 22, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10-11-0561

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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