Comparison of fixed and individualized regimen of vancomycin in achievement to recommended blood concentration based on clinical guidelines in critically ill patients.
Objective: The aims of this study are to evaluation of vancomycin dosing in critically ill patients and comparison with standard treatment guidelines for rational prescribing of medicine.
Design: Critically ill patients (N=64) who received vancomycin during their treatment course will be randomized in two groups.
Setting and conduct: This study will be performed in two phases. In the first phase, serum concentrations of vancomycin will be measured without any intervention and pharmacokinetic parameters of patients will be calculated. In the second phase, patients will be randomized in two groups. One of the groups will be received fixed dose of vancomycin and in the other one, the dose will be individualized based on serum concentrations.
Participants: Critically ill patients with evidence of sepsis, survival prognosis > 72 hours and Glomerular filtration rate (GFR) > 60 ml/min will be enrolled to the study. Acute renal failure, adverse drug reaction and discontinuation of vancomycin within 72 hours are the major exclusion criteria.
Intervention: After administration of vancomycin, serum concentrations of vancomycin will be measured at different points and dosage will be adjusted and individualized.
Main outcome measures: Peak and trough concentration of vancomycin in critically ill patients, Comparison of dosing with standard treatment guidelines, Correlation of different variables such as Serum creatinin and mechanical ventilation to pharmacokinetic parameters of vancomycin.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT201209291497N2
Registration date:2012-10-26, 1391/08/05
Registration timing:registered_while_recruiting
Last update:
Update count:0
Registration date
2012-10-26, 1391/08/05
Registrant information
Name
Sarah Mousavi
Name of organization / entity
Clinical Pharmacy Department, Pharmacy Faculty, Isfahan University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 31 3792 2567
Email address
smousavi@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Vice chancellor of research, Tehran University of Medical Sciences
Expected recruitment start date
2012-10-22, 1391/08/01
Expected recruitment end date
2014-06-22, 1393/04/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Comparison of fixed and individualized regimen of vancomycin in achievement to recommended blood concentration based on clinical guidelines in critically ill patients.
Public title
Adjustment of vancomycin dosage in critically ill patients.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria: Age over 18 years, Glomerular Filtration Rate (GFR) > 60 ml/min, evidence of sepsis, survival prognosis> 72 hours, the lack of sensitivity to the drug, drug administration in past 72 hours.
Exclusion criteria: Patient death within 72 hours of the beginning of the study, acute renal failure during the study (according to the criteria of RIFLE), adverse drug reaction, change of treatment during the first 72 hours of treatment, discontinuation of drug during the first 72 hours of treatment, the loss of the samples of the first 48 hours, no individualization during the initial 48 hours of treatment.
Age
From 18 years old to 70 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size:
64
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethic Committee of Tehran University of Medical Sciences
Street address
Fourth floor, Central Organization of Tehran University of Medical Sciences, Corner of Ghods Street, Keshavarz Blvd.
City
Tehran
Postal code
Approval date
2012-09-23, 1391/07/02
Ethics committee reference number
91-02-156-18212-65308
Health conditions studied
1
Description of health condition studied
sepsis
ICD-10 code
A41.0
ICD-10 code description
Sepsis due to Staphylococcus aureus
Primary outcomes
1
Description
Cumulative dose
Timepoint
First 72 hours of treatment
Method of measurement
sum of the used dose based on patient chart
2
Description
Maximum concentration of drug in steady state
Timepoint
After at least 3 half- life, or changing the dose
Method of measurement
ELISA KIT
3
Description
Minimum concentration of drug in steady state
Timepoint
After at least 3 half- life, or changing the dose
Method of measurement
ELISA KIT
4
Description
Mean of the intervention for dose adjustment
Timepoint
Number of dose adjustment based on pharmacokinetic data
Method of measurement
Evaluation of recorded intervention on patient's chart
Secondary outcomes
1
Description
Positive Expiratory End Pressure(PEEP)
Timepoint
Each time patient received vancomycin
Method of measurement
Patient chart
2
Description
Tidal volume
Timepoint
Each time patient received vancomycin
Method of measurement
Patient chart
3
Description
Serum creatinin
Timepoint
Each time patient received vancomycin
Method of measurement
Patient chart
4
Description
Mean Arterial Pressure
Timepoint
Each time patient received vancomycin
Method of measurement
Patient chart
5
Description
Urine Output
Timepoint
Each time patient received vancomycin
Method of measurement
Patient chart
Intervention groups
1
Description
In the first phase, due to the uncertainty constant serum concentrations of fixed dose regimen -in patients who have indications for treatment with vancomycin- serum concentrations of vancomycin for 4 consecutive first dose, with loading dose of 25mg/kg and then 15 mg/kg/dose every 12 hours will be measured without any intervention. Pharmacokinetic parameters of patients will be calculated. After ensuring the patient's kinetic parameters, the second phase of the study will be conducted.
Category
Treatment - Drugs
2
Description
Phase 2:
At this stage, patients are divided randomly (block randomization based on block size 4) into two groups. The first group of patients will be treated using a fixed-dose protocol of 25mg/kg/stat then 15mg/kg/dose every 12 hours and then serum concentrations will be evaluated at 8 times: 1- end of infusion of first dose 2- second dose trough 3- third dose trough 4- fourth dose trough 5- fifth dose trough 6- sixth dose trough 7- eleventh dose trough 8- trough at 15 dose.
In second group, vancomycin will be administered with a loading dose of 25mg/kg/stat and then will be individualized. Drug concentration will be measured at 9 times: 1- end of infusion of first dose 2- second dose trough 3- third dose trough 4- second dose peak 5- 6-8 hours after third dose 6- third dose trough 7- fourth dose trough 8- sixth dose trough 9- seventh dose trough. And then treatment will be continued based on fixed dose protocol and physician order.
Category
Treatment - Drugs
3
Description
Patients who have the inclusion criteria will be enrolled to the study and received vancomycin (Jaber Ebne Hayyan Pharmaceutical Co., Tehran, Iran) through Intravenous infusion (at least 1 hour), with loading dose of 25mg/kg and then 15 mg/kg/dose every 12 hours. Depending on the phase of study, serum concentrations will be evaluated and vancomycin dosage will be adjusted. Patients will be followed up for 7 days and vancomycin dosage will be individualized for them.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Sina Hospital
Full name of responsible person
Sarah Mousavi
Street address
5th Floor,No. 92, Karimkhan Street, Hafte- Tir Square
City
Tehran
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Vice chancellor for research, Tehran University of Medical Sciences
Full name of responsible person
Dr Akbar Fotouhi
Street address
Fourth floor, Central Organization of Tehran University of Medical Sciences, Corner of Ghods Street, Keshavarz Blvd.
City
Tehran
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Vice chancellor for research, Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
Clinical Pharmacy Department, School of Pharmacy, Tehran University of Medical Sciences