Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001297617
Ethics application status
Not yet submitted
Date submitted
18/11/2014
Date registered
11/12/2014
Date last updated
11/12/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Concentration of prophylactic intraosseous regional vancomycin administration prior to total knee arthroplasty in the obese patient
Scientific title
Randomized controlled trial of intraosseous regional vancomycin prior to total knee arthroplasty in the obese population compared with systemic vancomycin administration with the primary outcome of tissue concentration
Secondary ID [1] 285699 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection following total knee arthroplasty 293556 0
Condition category
Condition code
Surgery 293842 293842 0 0
Surgical techniques
Infection 293919 293919 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients would be randomised to two groups.

Both groups would receive 1g systemic IV cefazolin 15 minutes prior to tourniquet inflation. This ensures all patients in the study receive effective antibiotic prophylaxis regardless of randomisation. Both groups of patients would then undergo routine prep and draping prior to exsanguination and inflation of an above knee tourniquet to 300mmHg.

Immediately following inflation, the intervention group would receive 500mg of vancomycin via an EZ-IO (Vidacare, San Antonio, Texas) intraosseous cannula.
Intervention code [1] 290641 0
Prevention
Comparator / control treatment
The control group would receive 15mg/kg based on actual body weight (maximum of 2g) of IV vancomycin
Control group
Active

Outcomes
Primary outcome [1] 293620 0
Fat and bone concentration of vancomycin from seven tissue samples. Four fat samples and three bone samples.
Timepoint [1] 293620 0
At 4 time points intraoperatively.
Post incision
Distal femoral cut
Component trialling
Prior to closure
Secondary outcome [1] 311481 0
Adverse effects
- Infusion related events
During or soon after infusion of vancomycin, patients may develop flushing of the upper body ("red neck") or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes, but may persist for several hours. Such events are infrequent if vancomycin is given by a slow infusion and at an appropriate dilution, and can be treated effectively with antihistamines.
- Renal
Rarely, renal failure, principally manifested by increased serum creatinine or urea concentrations, especially in patients given large doses of vancomycin, has been reported. .



Assessment of adverse events
- Patients will be followed closely through their 45
days as an inpatient following surgery and then regular clinic
appointments.

During the the operation, patient safety will be monitored by full cardiovascular and anaesthetic monitors. Following
surgery patients will spend 12 hours in recovery again with full monitoring and 1 to 1 nursing supervision.

Adverse events will be recorded and reviewed by an independent research nurse specialist
Timepoint [1] 311481 0
Intraoperatively
Post-operative inpatient period

Eligibility
Key inclusion criteria
Undergoing primary total knee replacement
Informed consent given
Age>55
Age<85
BMI greater than or equal to 35
Minimum age
55 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous compartment syndrome
Allergy to antibiotics used in the study
Abnormal cardiac, renal or liver function
Concurrent nephrotoxic medications
BMI <35

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be identified by using the waiting list of the study investigators. They will be direct offers of participation at preadmission clinics.

Sealed envelopes opened at time of enrolment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random sequence
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis
Power was calculated based on our previous randomization control trial of comparing intraosseous administration vs. systematic administration of vancomycin. The mean tissue concentrations of vancomycin in subcutaneous fat and bone was 40.3 (+/-47.2) in the intraosseous group and 3.6 (+/-2.2) in the systemic group.
10 patients in each arm will be expected to provide the summary of concentration in bone, fat, and blood samples.

Means, standard deviations, and the 95% confidence limits will be calculated for the concentrations in the different samples. Different tissue samples will be pooled according to surgical steps. Coefficient of variations (CV) of concentration level will be summarized at each surgical step for the comparison between three arms. Repeat measure analysis of variance will be used to compare the average level of concentration across time between groups adjusted by diabetes, age, and length of surgical procedure; Shapiro-Wilk test will be used to assess the normality of the residuals.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/12/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment outside Australia
Country [1] 6485 0
New Zealand
State/province [1] 6485 0
Auckland

Funding & Sponsors
Funding source category [1] 290270 0
Charities/Societies/Foundations
Name [1] 290270 0
New Zealand Orthopaedic Association
Country [1] 290270 0
New Zealand
Primary sponsor type
Individual
Name
Seung Joon Chin
Address
North Shore Hospital
Waitemata District Health Board
124 Shakespeare Road
Westlake
0620
Auckland
Country
New Zealand
Secondary sponsor category [1] 288977 0
Individual
Name [1] 288977 0
Mr Simon Young
Address [1] 288977 0
North Shore Hospital
Waitemata District Health Board
124 Shakespeare Road
Westlake
0620
Auckland
Country [1] 288977 0
New Zealand

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 291966 0
Health and Disability Ethics Committee
Ethics committee address [1] 291966 0
Ministry of Health
Ethics Department
Level 13
20 Aitken Street
Thorndon
6011
Wellington
Ethics committee country [1] 291966 0
New Zealand
Date submitted for ethics approval [1] 291966 0
21/11/2014
Approval date [1] 291966 0
Ethics approval number [1] 291966 0

Summary
Brief summary
The aim of the proposed study is to assess the concentration of vancomycin for prophylactic total knee arthroplasty in the obese patient.

Infection remains a devastating complication to total knee joint arthroplasty. Obesity (BMI>30) has been shown in a meta-analysis of 150000 patients to have a significantly higher incidence of deep and superficial infections with an odds ratio of 2.4 and 2.2 respectively.

Intraosseous regional administration (IORA) has been validated to produce higher tissue concentration of vancomycin compared to systemic administration in a study performed by the project leader that recently received the Mark Coventry Award.

The pathophysiology of obesity alters the pharmacokinetics of vancomycin with a higher volume of distribution and a shorter elimination half-life. Thus the systemic dose of vancomycin increases according to body weight. The significance of this for regional antibiotics is unknown.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52886 0
Dr Seung Joon Chin
Address 52886 0
North Shore Hospital
Orthopaedics Department
124 Shakespeare Road
Westlake
0622
Auckland
Country 52886 0
New Zealand
Phone 52886 0
+64211571063
Fax 52886 0
Email 52886 0
sjoonchin@gmail.com
Contact person for public queries
Name 52887 0
Seung Joon Chin
Address 52887 0
North Shore Hospital
Orthopaedics Department
124 Shakespeare Road
Westlake
0622
Auckland
Country 52887 0
New Zealand
Phone 52887 0
+64211571063
Fax 52887 0
Email 52887 0
sjoonchin@gmail.com
Contact person for scientific queries
Name 52888 0
Seung Joon Chin
Address 52888 0
North Shore Hospital
Orthopaedics Department
124 Shakespeare Road
Westlake
0622
Auckland
Country 52888 0
New Zealand
Phone 52888 0
+64211571063
Fax 52888 0
Email 52888 0
joon89@gmail.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23364Study protocol    Available via email
23365Informed consent form    Available via email
23366Ethical approval    Available via email

Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4502Study results articleYes The AAHKS Clinical Research Award: Intraosseous Re... [More Details]

Documents added automatically
No additional documents have been identified.