Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000006640
Ethics application status
Approved
Date submitted
10/12/2013
Date registered
3/01/2014
Date last updated
26/07/2022
Date data sharing statement initially provided
27/03/2019
Date results information initially provided
26/07/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Does the use of intravascular ultrasound improve outcomes of endovascular interventional procedures for peripheral vascular disease of the superficial femoral artery or popliteal artery?
Scientific title
In patients with peripheral vascular disease of the superficial femoral artery or popliteal artery, does the use of intravascular ultrasound and angiography in combination improve the outcome of endovascular interventional procedures, as measured by 1 year primary patency rates, in comparison to the use of angiography alone?
Secondary ID [1] 283729 0
NIL
Universal Trial Number (UTN)
Nil
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral Arterial Disease 290698 0
Condition category
Condition code
Cardiovascular 291066 291066 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will involve patients undergoing endovascular intervention (angioplasty +/- stenting) for stenosis/occlusion of the superficial femoral artery (SFA) and/or popliteal artery. Imaging guidance is essential for the success of these procedures. Traditionally this guidance has been performed by the use of angiographic imaging. In this intervention intravascular ultrasound will be added as an adjunctive imaging method in additional to angiography. Previous observational studies in the peripheral arteries and studies from the coronary circulation suggest that the use of intravascular ultrasound allows for more accurate sizing of lesion and vessels and more precise balloon and stent sizing and placement. The addition of intravascular ultrasound adds an extra 15 minutes to the length of the procedure. It is hypothesized that the additional of intravascular ultrasound will result in better technical results for the interventional procedure and so reduce complication rates.
Intervention code [1] 288424 0
Treatment: Devices
Comparator / control treatment
The intervention group group will have the procedure guided by a combination of intravascular ultrasound and angiography. The comparator group will have the procedure guided by angiography alone (standard care).
Control group
Active

Outcomes
Primary outcome [1] 291059 0
Binary restenosis at 12 months- defined as <50% restenosis in the treated segment of the artery. The duplex criteria is a peak velocity ratio >/= 2.4. Duplex ultrasound will be used as the standard non-invasive surveillance modality. Regular surveillance scans will be performed at 3,6 and 12 months, CT, MRI or angiography may also be used if performed for clinical requirements and a 50% reduction in lumen will indicate restenosis in these cases
Timepoint [1] 291059 0
1, 3, 6 and 12 months post procedure
Secondary outcome [1] 305903 0
Target lesion revascularisation (TLR) rate - defined as the number of re-interventions performed on treated lesions divided by the total number of primary treatments
Timepoint [1] 305903 0
One year post procedure
Secondary outcome [2] 305904 0
Major adverse events (MAEs) - defined as death, cardiovascular event (MI and stroke), target lesion revascularisation (TLR) and major amputation
Timepoint [2] 305904 0
One year post procedure

Eligibility
Key inclusion criteria
Patients with a stenotic or occlusive lesion(s) in the SFA or popliteal artery in whom endovascular intervention with angioplasty +/- stenting is the most appropriate treatment option based on presenting symptoms, lesion characteristics and medically suitability.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are unable to give informed consent due to language difficulties, or physical and/or mental incapacity.
Allergy to iodine based contrast media.
Very short life expectancy (>6 months)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patient will be enrolled in the study at the time of booking for the procedure (usually in the out-patient clinic or the hospital ward), at least one day before the procedure. The patient will be randomised at the time of the procedure with the interventionist unaware of the randomisation until after the pre-intervention angiography has been performed (to reduce the chance of bias from changes in angiographic methods due to knowledge of whether intravascular ultrasound data will be available during the procedure). Randomisation will be concealed through the use of an online random number generator that will accessed for allocation the subject at the time of the procedure (this is after the time of enrollment in the study).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table generated by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The main research question regarding differences in percentage of cases that do not have a >/=50% restenosis and have not required re-intervention between treatment and control group will be addressed utilizing survival analysis. Required sample size was estimated using Log-rank tests subroutine 7 available in PASS 8 sample size estimation software. An overall sample size of 117 subjects (58 in the control group and 59 in the treatment group) will achieve 80% power at a 0.05 significance level to detect a hazard ratio of 0.51 when the proportion surviving in the control group is 0.5. The accrual pattern across time periods is uniform (all periods equal). Hypothesised proportion of cases that do not develop restenosis requiring re-intervention in one year in the control (angiography only) group is 0.5 which is in line with the reported combined literature for angioplasty and stenting. The hypothesised proportion of cases that do not require re-intervention (primary patency) in one year in the treatment (IVUS and angiography) group is equal 0.7. Due to the lack of data in peripheral vascular arteries this estimate has been driven by results from the coronary artery literature. Due to concerns about the generalisability of the coronary evidence to peripheral arteries, the estimated effect of the use of IVUS has been set at the lower end of that stated in the literature. The final required sample size will be overestimated by 25% to accommodate anticipated missing data (based on local data for death rate and loss to follow-up) resulting in 74 subjects to be enrolled in each arm of the trial.
Finally, agreement analyses will be undertaken to assess the degree of equivalence of various quantifiable blood vessels characteristics obtained from angiography and IVUS. The analyses will include reporting Bland-Altman limits of agreement. Fixed and proportional biases will be assessed with attention given to using an approach which will appropriate address that neither angiography or IVUS can be perceived as “golden standard”. Sample size determined by the primary outcome considerations should be more than sufficient for assessing agreement as per various rules of thumb reported in the agreement literature.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2014
Actual
9/08/2014
Date of last participant enrolment
Anticipated
16/03/2020
Actual
11/03/2020
Date of last data collection
Anticipated
15/03/2021
Actual
16/04/2021
Sample size
Target
150
Accrual to date
Final
150
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1847 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 7631 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 288409 0
Hospital
Name [1] 288409 0
Flinders Medical Centre
Country [1] 288409 0
Australia
Primary sponsor type
Hospital
Name
Department of Vascular Surgery, Flinders Medical Centre
Address
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia 5042
Country
Australia
Secondary sponsor category [1] 287110 0
None
Name [1] 287110 0
Address [1] 287110 0
Country [1] 287110 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290286 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 290286 0
The Flats G5 – Rooms 3 and 4
Flinders Drive
Bedford Park
South Australia 5042
Ethics committee country [1] 290286 0
Australia
Date submitted for ethics approval [1] 290286 0
04/09/2013
Approval date [1] 290286 0
27/09/2013
Ethics approval number [1] 290286 0
453.13

Summary
Brief summary
Narrowing or occlusion of the arteries of the lower limb, caused by atherosclerotic lesions, can lead to leg pain, ulceration and ultimately amputation. Endovascular revascularisation is a procedure in which the artery opened through the use of balloons or stents inserted under the guidance of a special x-ray technique called angiography. These procedures have a high rate of failure with about half developing a >/=50% narrowing (or restenosis) within a year. Much of this failure rate is attributed to technical factors such as incorrect size of catheter or incorrect positioning and in part may relate to the limited view provided by angiography. Intravascular ultrasound (IVUS) is an alternative imaging method that provides a more complete view of the artery. It has been shown that IVUS adds more information when combined with angiography but it is unclear whether this results in changes to treatment and whether this then results in better outcomes for patients.
This aim of this study is to investigate whether the addition of IVUS improves the outcomes for endovascular revascularisation.
This is a randomised control trial comparing endovascular revascularisation procedures guided by angiography with procedures guided by both angiography and IVUS. The study sample of 150 patients will be recruited from patients requiring treatment of lesions in the superficial femoral or popliteal arteries. Patients will be randomised into two groups of equal size; a control group having angiography guidance only and a second group having both angiography and IVUS guidance. All patients will have non-invasive tests of endothelial function (tests of the functioning the inner surface of the artery – an essential component in maintaining vascular wellbeing) before their and after the procedure as well as the standard blood tests and regular surveillance imaging that is normally scheduled for patients after these procedures.
The primary outcome measure will be >/=50% restenosis of the treated artery. This degree of restenosis requires re-intervention to reopen the artery. At this point the original procedure will be deemed to have failed for the purposes of analysis. The restenosis rate will be compared for each group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44846 0
Mr Richard Allan
Address 44846 0
Dept of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia 5042
Country 44846 0
Australia
Phone 44846 0
+61 402395505
Fax 44846 0
Email 44846 0
[email protected]
Contact person for public queries
Name 44847 0
Mr Richard Allan
Address 44847 0
Dept of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia 5042
Country 44847 0
Australia
Phone 44847 0
61 8 82046796
Fax 44847 0
Email 44847 0
[email protected]
Contact person for scientific queries
Name 44848 0
Mr Richard Allan
Address 44848 0
Dept of Vascular Surgery
Flinders Medical Centre
Flinders Drive
Bedford Park
South Australia 5042
Country 44848 0
Australia
Phone 44848 0
61 8 82046796
Fax 44848 0
Email 44848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics committee approval for IPD sharing has not requested


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Allan RB, Puckridge PJ, Spark JI, Delaney CL. The ... [More Details]
Other filesNo "IVUS vs. angiography-guided femoropopliteal revas... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAccuracy and Reliability of Peripheral Artery Calcium Scoring Systems Using an Intravascular Ultrasound Reference Standard.2023https://dx.doi.org/10.1016/j.avsg.2022.11.014
EmbaseComparison of Angiographic Dissection Classification Systems in the Femoropopliteal Arteries Using IVUS Validation and Reliability Testing.2022https://dx.doi.org/10.1177/15266028211047952
EmbaseThe Impact of Intravascular Ultrasound on Femoropopliteal Artery Endovascular Interventions: A Randomized Controlled Trial.2022https://dx.doi.org/10.1016/j.jcin.2022.01.001
N.B. These documents automatically identified may not have been verified by the study sponsor.