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Use of a Loading Dose of Vancomycin in Pediatric Dosing

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ClinicalTrials.gov Identifier: NCT01290237
Recruitment Status : Terminated (PI leaving institution, slow enrollment)
First Posted : February 4, 2011
Results First Posted : March 5, 2018
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Alicia Demirjian, Boston Children’s Hospital

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Infection Drug: vancomycin hydrocloride Not Applicable

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  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Use of a Loading Dose of Intravenous Vancomycin Will Achieve Therapeutic Concentration Earlier Than Conventional Pediatric Dosing: A Randomized Controlled Trial
Study Start Date : February 2011
Actual Primary Completion Date : February 2012
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: 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 Name: Vancomycin



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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



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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01290237


Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children’s Hospital
Investigators
Principal Investigator: Alicia A Demirjian, MD Boston Children’s Hospital

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alicia Demirjian, Clinical Fellow, Pediatric Infectious Diseases, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT01290237     History of Changes
Other Study ID Numbers: 10-11-0561
First Posted: February 4, 2011    Key Record Dates
Results First Posted: March 5, 2018
Last Update Posted: March 29, 2018
Last Verified: March 2018

Keywords provided by Alicia Demirjian, Boston Children’s Hospital:
vancomycin
loading dose
pharmacokinetic
pediatric
Methicillin-Resistant Staphylococcus aureus (MRSA)
Serious infection with Gram positive bacteria

Additional relevant MeSH terms:
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents