- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01290237
Use of a Loading Dose of Vancomycin in Pediatric Dosing
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.
Studieoversigt
Detaljeret beskrivelse
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%.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- Children's Hospital Boston
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-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: Vancomycin loading dose
Intervention: administer intravenous vancomycin 30 mg/kg/dose once, followed 8 hours later by 20 mg/kg/dose every 8 hours
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see description of study arms
Andre navne:
|
Aktiv komparator: Control
No intervention.
Administer intravenous vancomycin 20 mg/kg/dose every 8 hours as per hospital guideline.
|
see description of study arms
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Count of Participants With Vancomycin Trough Between 15 and 20
Tidsramme: 8 hours after the first dose of vancomycin
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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
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8 hours after the first dose of vancomycin
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
AUC/MIC for Vancomycin in the Study Population
Tidsramme: within 48 hours after receiving the first dose of vancomycin
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AUC/MIC using hypothetical MIC = 1 mg/L
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within 48 hours after receiving the first dose of vancomycin
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Alicia A Demirjian, MD, Boston Children's Hospital
Publikationer og nyttige links
Generelle publikationer
- Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4. Erratum In: Clin Infect Dis. 2011 Aug 1;53(3):319.
- Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. doi: 10.2146/ajhp080434. No abstract available. Erratum In: Am J Health Syst Pharm. 2009 May 15;66(10):887.
- Frymoyer A, Hersh AL, Benet LZ, Guglielmo BJ. Current recommended dosing of vancomycin for children with invasive methicillin-resistant Staphylococcus aureus infections is inadequate. Pediatr Infect Dis J. 2009 May;28(5):398-402. doi: 10.1097/INF.0b013e3181906e40.
- Demirjian A, Finkelstein Y, Nava-Ocampo A, Arnold A, Jones S, Monuteaux M, Sandora TJ, Patterson A, Harper MB. A randomized controlled trial of a vancomycin loading dose in children. Pediatr Infect Dis J. 2013 Nov;32(11):1217-23. doi: 10.1097/INF.0b013e3182a26774.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 10-11-0561
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