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Trial registered on ANZCTR


Registration number
ACTRN12618001895279
Ethics application status
Approved
Date submitted
18/11/2018
Date registered
21/11/2018
Date last updated
5/04/2019
Date data sharing statement initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetic clearance of vancomycin using two different dialyzers
Scientific title
A pK study comparing the clearance of Vancomycin during haemodialysis using Medium cut-off membrane (Theranova) and High-Flux membranes (Revaclear
Secondary ID [1] 296634 0
Hawke’s Bay District Health Board Research Application – Reference 18/09/305
Universal Trial Number (UTN)
U1111-1224-1398
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
end stage renal failure
310460 0
Condition category
Condition code
Renal and Urogenital 309175 309175 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In centre haemodialysis patients needing (Vancomycin: drug of the study) as deemed necessary by their dialysis doctor, will be enrolled in the study. Vancomycin will be given over 6 dialysis sessions based on trough concentration. We understand how vancomycin is cleared on Revaclear but not on Theranova, therefore, subjects' dialysis sessions will alternate between Revaclear and Theranova dialyzers. During the study, we will look at vancomycin clearance on the two diffierent dialysers.

The duration of each dialysis session will depend on patients' dialysis prescription before the study. the minimum is 4 hours per session and maximum is 5 hours. Patients are usually prescribed 3 session per week (either Mon, Wed, Friday) or (Tues, Thurs, Sat).

Before the study starts, patients will already be on Theranova. so loading dose of vancomycin will be on Theranova. The first dialysis session (day 1 of study), patient will be start with Theranova. Day 2 will be on Revaclear, day 3 will be on Theranova, day 4 will be on Revaclear, day 5 will on Theranova and day 6 will on Revaclear. then patient will be returned to Theranova permanently.

The principal investigator will be responsible for reviewing subjects each session along with reading notes, reviewing nursing notes, talking to patients and signing of the patient data sheet for each treatment. This is a pilot study and numbers are small so it can be done. We would also ask one of the co-investigators to review notes to make sure nothing was missed out around data collection time.

The loading dose of vancomycin is 30mg/kg on day 0 as prescribed by the dialysis doctor. The next dose will depend on vancomycin trough concentration (i.e. before starting dialysis). A maintenance dose of 10 – 15 mg/kg will be administered at each session when pre-dialysis concentration is less than or equal to 20 mg/L in infections. The dose will be delivered in the last 60-120 minutes of a dialysis session. The maximum dose delivered would be 2000mg. The Principle Investigator will review all test results and adverse events reported prior to the next dose. The dose will be adjusted based on review of pre-dialysis vancomycin concentration by the Principle investigator. Dose adjustments will be made in an approximately linear fashion in accordance with trough plasma levels. For example, an increase in dose by 50% would result in an increase in trough level by approximately 50% and vice versa
Intervention code [1] 312943 0
Treatment: Devices
Comparator / control treatment
The comparator/control goup are same subjects but when dialysed on Revaclear as we know that around 20% of vancomycin in cleared no Revaclear over 3 hours of haemodialysis.
Control group
Active

Outcomes
Primary outcome [1] 308147 0
To compare the drug clearance profile of vancomycin when administered during the use of Medium cut-off membrane (Theranova) with high flux dialysers (Revaclear) in haemodialysis patients

Vancomycin drug concentrations (start of dialysis session, then at 5, 15, 30, 45, 120 minutes after starting dialysis, and 30 minutes post dialysis session) will provide a pharmacokinetic profile, including AUC0-inf, Tmax, Cmax, and Cmin, and will be calculated for each subject
Timepoint [1] 308147 0
6 sessions of Haemodialysis over 2 weeks
Secondary outcome [1] 354077 0
Obtaining Adverse Events: All volunteered, elicited and observed adverse events (AEs) will be documented


E.g. 1. known/possible Red man syndrome--> will be assessed by looking at skin, subjects' vitals
2.analphylaxis--> assessed by looking at subject clinically and looking at their vitals too. this will be done by investigators as well as dialysis nurses and technicians
3. skin reaction such as DRESS will be assessed by looking at skin by investigators and dialysis nurses/technicians.
4. thrombophlebitis: will be assessed by dialysis nurses and technician
Timepoint [1] 354077 0
6 Haemodialysis sessions over 2 weeks period

Eligibility
Key inclusion criteria
The following are the inclusion criteria:

1. Male or female over the age of 18.
2. Be an In-centre haemodialysis subject using a middle cut-off dialyser (Theranova)
3. Female subjects of child bearing age must have a negative serum pregnancy test at baseline
4. Females of child-bearing potential must be non-pregnant and not lactating at the time of the study
5. Not allergic or have had an adverse reaction to vancomycin previously
6. Provide written informed consent
7. Have the ability to understand the requirements of the study and to comply with the study protocol and dosing regimen
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects will be excluded from the study if they:

1. Have clinical evidence of any active significant disease that could potentially compromise the ability of the investigator to evaluate or interpret the effects of the study treatment on safety assessment and thus increase the risk to the subject to unacceptable levels
2. Are on other concomitant antibiotics at the time of the study
3. Are pregnant or nursing
4. Have a history of allergy to vancomycin
5. Are considered by the Investigator to be an unsuitable candidate for this study
6. Are on hemodiafiltration (HDF)
7. Have sensitivity (allergic reaction) to Revaclear or Theranova membranes

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
no sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
it is a small pilot study comparing vancomycin clerance during haemodilaysis on two different dialysers (Theranova Vs Revaclear)
Phase
Not Applicable
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
- Study sample: No formal power or sample size calculations were made. The data collected will be used to estimate possible effect size and variability of measures and allow us to assess drug clearance. A total of 6 volunteers on haemodialysis presenting with an acute infection/indication requiring vancomycin will participate. This will allow us a maximum of 36 sessions to obtain data. In general, all the analyses considered exploratory and are designed to give some insight into the relationship between the treatment and potential outcomes.

- Baseline characteristics of subjects will be summarised by descriptive statistics
- Safety parameters at each follow-up assessment, as well as changes from baseline, will be examined. Safety will also be assessed through the recording of adverse events, monitoring of vital signs and vascular access
- AUC, Tmax, Cmax and Cmin will be calculated for each subject.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21043 0
New Zealand
State/province [1] 21043 0
Hawkes Bay

Funding & Sponsors
Funding source category [1] 301206 0
Hospital
Name [1] 301206 0
Hawkes Bay DHB Renal research Fund, Hastings hospital
Address [1] 301206 0
Renal services
Hawkes Bay (Hastings) hospital

Private Bag 9014
Hastings 4156
Country [1] 301206 0
New Zealand
Primary sponsor type
Hospital
Name
Hastings hospital
Address
Renal services
Hawkes Bay (Hastings) hospital

Private Bag 9014
Hastings 4156
Country
New Zealand
Secondary sponsor category [1] 300838 0
None
Name [1] 300838 0
Address [1] 300838 0
Country [1] 300838 0
Other collaborator category [1] 280433 0
Individual
Name [1] 280433 0
Dr. Colin Hutchison
Address [1] 280433 0
Renal services
Hawkes Bay hospital

Private Bag 9014
Hastings 4156
Country [1] 280433 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301952 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 301952 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 301952 0
New Zealand
Date submitted for ethics approval [1] 301952 0
27/11/2018
Approval date [1] 301952 0
18/12/2018
Ethics approval number [1] 301952 0
18/CEN/252

Summary
Brief summary
Vancomycin is commonly used in dialysis patients. Vancomycin is washed out on dialysis. We are currently using Theranova dialyser compared to previously Revaclear. We hypothesis that Theranova will have higher clearance of vancomycin when compared to Revaclear. During the study, if you are on Vancomycin, then we will alternate the dialyser (filter) between each session for a total of six sessions over 2 weeks period. Blood test will be done during the study to help us understand how antibiotics is cleared.
Trial website
not available
Trial related presentations / publications
nil
Public notes
nil

Contacts
Principal investigator
Name 88650 0
Dr Hussain Allawati
Address 88650 0
Renal Services
Hastings Hospital
Hawkes bay DHB
private bag 9014
Hastings 4156
Country 88650 0
New Zealand
Phone 88650 0
+64 2105597141
Fax 88650 0
Email 88650 0
hussain.allawati@hbdhb.govt.nz
Contact person for public queries
Name 88651 0
Dr Hussain Allawati
Address 88651 0
Renal Services
Hastings Hospital
Hawkes bay DHB
private bag 9014
Hastings 4156
Country 88651 0
New Zealand
Phone 88651 0
+64 2105597141
Fax 88651 0
Email 88651 0
hussain.allawati@hbdhb.govt.nz
Contact person for scientific queries
Name 88652 0
Dr Hussain Allawati
Address 88652 0
Renal Services
Hastings Hospital
Hawkes bay DHB
private bag 9014
Hastings 4156
Country 88652 0
New Zealand
Phone 88652 0
+64 2105597141
Fax 88652 0
Email 88652 0
hussain.allawati@hbdhb.govt.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All information provided to the investigators will be kept strictly confidential and confined to the clinical personnel involved in conducting the study as part of the permanent record. All data and information gathered for each subject will be identified only by a unique subject study number. Individual information obtained will not be disclosed except when the data are needed by their personal physician or other medical personnel responsible for their care. At conclusion of the study, the blood samples obtained will be discarded at the local laboratory.
the reason is to do with confidentiality
What supporting documents are/will be available?
Study protocol
Informed consent form
How or where can supporting documents be obtained?
Type [1] 295 0
Study protocol
Citation [1] 295 0
Link [1] 295 0
Email [1] 295 0
Other [1] 295 0
study protocol
Type [2] 296 0
Informed consent form
Citation [2] 296 0
Link [2] 296 0
Email [2] 296 0
Other [2] 296 0
patient information and informed consent sheet
Summary results
No Results