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Trial registered on ANZCTR


Registration number
ACTRN12618001092280
Ethics application status
Approved
Date submitted
20/06/2018
Date registered
29/06/2018
Date last updated
29/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
This trial examines the effectiveness of an angioplasty balloon coated with an anticancer drug (Paclitaxel) compared to an ordinary, uncoated balloon in preventing recurrent hemodialysis fistula narrowings in patients on hemodialysis for renal failure.
Scientific title
A double blinded, multicentre, randomised control trial comparing the effectiveness of the Paclitaxel drug eluting angioplasty balloon with an ordinary angioplasty balloon in preventing restenosis and re-intervention in the treatment of recurrent autogenous hemodialysis fistula stenoses in the hemodialysis population of three participating Australian Hospitals.
Secondary ID [1] 295257 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DEB in AVF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemodialysis fistula 308427 0
Arteriovenous fistula 308482 0
Condition category
Condition code
Renal and Urogenital 307415 307415 0 0
Kidney disease
Cardiovascular 307462 307462 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The addition of a Paclitaxel Drug Eluting Balloon, as opposed to the addition of a normal angioplasty balloon, to our Standard Endovascular Treatment of recurrent AV Hemodialysis Fistula stenoses to determine if this will reduce further restenosis at that site in a 12 month follow up period.
The dose of Paclitaxel delivered is 3 micrograms/mm2 of DEB surface area.
Biologically, the DEB should be left inflated for 30 seconds to allow drug translocation from the urea vehicle on the balloon to the target vessel; the company making the balloon (Medtronic) recommends 1 minute inflation time; our trial protocol stipulates 2 minutes of DEB inflation time. The inflation time for an ordinary angioplasty balloon is poorly determined and variable, depending on a number of factors. For our trial, patients in the control arm (Sham Balloon ie non-coated balloon), the inflation time of 2 minutes is also mandated in the trial protocol.
Our hemodialysis endovascular team compromises of Vascular Surgeons, Interventional Cardiologists and Interventional Nephrologists, often working together. A DEB intervention takes 3-4 minutes longer overall than a non-DEB intervention.
Our Operative Protocol specifies a number of strategies to ensure drug delivery to target vessel. They include: 1. Using the DEB sheath (in which the DEB is presented) to defeat the hemostatic valve on the access sheath and prevent drug loss a that point, 2. Minimising the time from the DEB entering the patient's circulation to full deployment (and measured and recorded for each trial entry), 3. Adequate inflation time, mandated at 2 minutes, again measured and recorded for each trial entry, and 4. A documented xray image of the fully deployed Trial Balloon at the Index Trial Area.
Intervention code [1] 301590 0
Treatment: Devices
Intervention code [2] 301591 0
Treatment: Drugs
Comparator / control treatment
Whereas the Trial Intervention group will receive a Paclitaxel Drug Eluting Angioplasty Balloon, the Control Group will receive a similar but non-drug coated balloon.
The Sham Balloon used in the Control arm is not part of the usual care. It is the addition of an extra angioplasty treatment to the Index Trial Area in the Sham arm of the trial.
The type of Sham Balloon is not mandated in the Trial Protocol; the size and length of the Sham Balloon is, off course, strictly mandated as described in the Trial Operative Protocol. The sham balloon must be 0.5mm bigger and the same length as the Index Trial Area.
Control group
Active

Outcomes
Primary outcome [1] 306389 0
The Primary Outcome is Late Lumen Loss, as measured at the narrowest point in the Index Trial Area of the Trial AV Fistula, on serial follow up ultrasound.
Timepoint [1] 306389 0
Trial follow up protocol is by scheduled ultrasounds combined with clinical review. Trial follow up time points are: 1. Baseline ultrasound (>24 hrs but <1 week post op), 2. Six weeks post op 3. Three months post op 4. Six months post op 5. One year post op. The Primary timepoint is 6 months post op.
In addition, any unexpected clinical problem with the Index Fistula during trial follow up would be assessed by ultrasound and clinically, and this non-scheduled ultrasound / clinical review is done according to trial protocol and becomes a time point in the trial.
Secondary outcome [1] 348319 0
The first Secondary Outcome was Re-Intervention to the Index Trial Area within the 12 month follow up period, including re-interventions performed after 12 months but determined by the findings of the 12 month (final) ultrasound scan.
For the purposes of the trial, both for the Trial intervention and for the Re-Intervention to ITA, we used our standard institutional indications. These are: A fistula stenosis with a luminal ultrasound diameter <2mm, or a luminal ultrasound diameter between 2-4mm with other evidence of fistula malfunction related to that stenosis. This includes prolonged decannulation bleeding, high venous return pressures, fistula flow (Qa) less than 500mls/min or inadequate dialysis flows.
Timepoint [1] 348319 0
1. Baseline ultrasound (>24 hrs but <1 week post op), 6 weeks post op, 3 months post op, 6 months post op, 12 months post op.
Secondary outcome [2] 348320 0
The second Secondary Outcome was Volume Flow (Qa) in the Trial Hemodialysis AV Fistula circuit, as measured in the feeding Brachial artery, by serial follow up ultrasound.
Timepoint [2] 348320 0
1. Baseline ultrasound (>24 hrs but <1 week post op), 6 weeks post op, 3 months post op, 6 months post op, 12 months post op.

Eligibility
Key inclusion criteria
1. Autogenous arterio-venous haemodialysis fistula 2. A recurrent stenosis 3. The ITA must be clearly visible on ultrasound using a 12 MHz + probe 4. The Trial Balloon must be at least 0,5 mm bigger than the largest angioplasty treatment balloon used in the SET. Because the biggest Medtronic DEB available is 7,5mm at burst pressure, patients subjected to angioplasty balloons > 7mm prior to randomisation were excluded. 5. Patient must consent to trial and be willing and able to attend the 5 post op follow-up ultrasounds.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of severe allergic reaction to contrast media or Paclitaxel. Intolerance to platelet blockade. Systemic coagulopathy or hypercoagulation disorders. Current active bleeding, bleeding in the past 12 months requiring blood transfusion or recent (< 3 months) intracranial haemorrhage. Thrombosed fistula. Where the fistula circuit contained a stent graft. Patient <18 years or unable to give informed consent. The patient is pregnant or pregnancy is planned during the study period. Central Vein Stenoses or fistula stenoses that cannot be interrogated by high frequency ultrasound probes (> 12 MHz). Patient unsuited for trial for social reasons eg lives too far away.

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)
Randomisation was by phone contact with the Randomisation Officer at the core lab.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size was calculated on a retrospective sample (from our prospective database) of LLL in the AVF after plain balloon angioplasty. This showed a LLL of 2.9mm over 12 months. With a hypothesised effect size of a 30% reduction in LLL with the application of a DEB, a resulting LLL of 2.0mm in the treatment arm was projected. This assumes that the expected effect size is 0.9mm, with an estimated standard deviation of outcome variable of 1.25mm. To achieve 99% power to detect this difference with a significance level of 5% with a 10% non-compliance rate, it was calculated that 75 subjects per group would be required. This calculation was done using the Analysis of Censored and Correlated Data – ACCorD.log statistical software. The hypothesised effect size of a 30% reduction in LLL was derived from the Sustained Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Lesions study (Dake, M.D., et al., Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the Zilver PTX randomized and single-arm clinical studies. J Am Coll Cardiol, 2013. 61(24): p. 2417-2427).

Recruitment
Recruitment status
Completed
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 in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11196 0
Wollongong Hospital - Wollongong
Recruitment hospital [2] 11197 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 11198 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 23057 0
2500 - Wollongong
Recruitment postcode(s) [2] 23058 0
2148 - Blacktown
Recruitment postcode(s) [3] 23059 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 299849 0
Commercial sector/Industry
Name [1] 299849 0
Medtronic corporation
Address [1] 299849 0
Medtronic Australasia Pty Ltd
2 Alma Rd, Macquarie Park NSW 2113
Country [1] 299849 0
Australia
Primary sponsor type
Hospital
Name
Western Renal, Westmead Hospital
Address
Western Renal Area Health Service,
Westmead Hospital,
Cnr Hawkesbury Road and Darcy Road Westmead NSW 2145,
Australia
Country
Australia
Secondary sponsor category [1] 299204 0
None
Name [1] 299204 0
Address [1] 299204 0
Country [1] 299204 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300726 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300726 0
Western Sydney Local Health District Research Office
Research & Education Network bldg
Westmead Hospital
Darcy Road
Westmead 2145
NSW, Australia
Ethics committee country [1] 300726 0
Australia
Date submitted for ethics approval [1] 300726 0
05/05/2014
Approval date [1] 300726 0
10/11/2014
Ethics approval number [1] 300726 0
HREC/ 14/WMEAD /181 (4010 )

Summary
Brief summary
AIM
To assess whether Drug Eluting Angioplasty Balloons (DEB) prevent recurrent narrowing in Arterio-Venous Fistulas (AVF).
The study is an investigator initiated, prospective, double blinded, randomised, multicentre, control trial conducted at 3 Australian institutions

BACKGROUND
When a patient’s kidneys fail, they will die unless some form of “renal replacement therapy” is provided.
Haemodialysis is a mainstay treatment in renal failure to keep patients alive in the short and long term.
Haemodialysis occurs when the patient’s blood is “washed” in a haemodialysis machine, which takes the place of the patient’s failed kidneys.
The biggest problem with haemodialysis is “haemodialysis access” i.e. repeatedly (3 to 5 times per week) placing two large bore needles into the patient’s blood vessels to circulate their blood through the haemodialysis machine.
The best form of haemodialysis access is the AVF - a swollen vein created surgically on the patient’s arm.
The commonest problem with the AVF is the development of narrowings (stenoses) in the AVF. This prevents proper haemodialysis – an immediately life threatening situation - and can lead to destruction of the AVF.
AVF stenoses are readily treated with angioplasty balloons – small balloons placed inside the narrowed part of the fistula – which “stretch” the narrowing and restore the AVF’s function.
The problem with this angioplasty treatment is that the body will attempt to “heal” the “stretched” narrowing and the narrowing will recur (restenosis). As a result, many haemodialysis patients require repeated treatments.
A new technology – DEB – has emerged to prevent this restenosis problem. DEBs are angioplasty balloons covered in a drug – Paclitaxel for our study – that blocks the restenosis process. The DEB is placed in the AVF immediately after a narrowing has been treated in the hope that it will prevent restenosis.
In the last 6 years, a similar technology - Drug Eluting Stents - have decreased restenosis after coronary artery angioplasty from 20% to 5%.
The use of Drug Elution in the AVF has not yet been investigated.

METHODS
We propose a multicentre, randomised control trial, comparing AVF stenoses treated with standard angioplasty techniques to AVF stenoses treated with standard techniques plus a DEB.
All trial patients will have their AVF stenosis treated by our current standard angioplasty protocol. In addition,
the STUDY GROUP and will receive a DEB to the treated stenosis and the CONTROL GROUP will receive a sham balloon.
Patients will be followed up with ultrasound of their fistula for one year to see if there is a difference in the rate of re-narrowing (restenosis) between the two groups.
Trial website
Trial related presentations / publications

Public notes
Attachments [6] 2794 2794 0 0

Contacts
Principal investigator
Name 84614 0
Dr Jan "John" Swinnen
Address 84614 0
c/o Department of Surgery,
Westmead Public Hospital,
Hawkesbury rd,
Westmead, 2145,
NSW
Australia
Country 84614 0
Australia
Phone 84614 0
+61 2 88908060
Fax 84614 0
+61 2 98937740
Email 84614 0
jan.john.swinnen@gmail.com
Contact person for public queries
Name 84615 0
Dr Jan "John" Swinnen
Address 84615 0
c/o Department of Surgery,
Westmead Public Hospital,
Hawkesbury rd,
Westmead, 2145
NSW
Australia
Country 84615 0
Australia
Phone 84615 0
+61 2 88908060
Fax 84615 0
+61 2 98937740
Email 84615 0
jan.john.swinnen@gmail.com
Contact person for scientific queries
Name 84616 0
Dr Jan "John" Swinnen
Address 84616 0
c/o Department of Surgery,
Westmead Public Hospital,
Hawkesbury rd,
Westmead, 2145
NSW
Australia
Country 84616 0
Australia
Phone 84616 0
+61 2 88908060
Fax 84616 0
+61 2 98937740
Email 84616 0
jan.john.swinnen@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary