Hypothesis, aims and design
Singapore General Hospital (SGH) is the oldest hospital in Singapore with many vascular access salvage procedures performed per year (~ 1400 cases per year).
We hypothesize that the 6-month circuit primary patency rates are not inferior in AVF treated with SCB compared to PCB. This single center, prospective and retrospective double arm registry study is a multi-investigator study that is conducted in accordance with the ethical principles in the Declaration of Helsinki and is approved by the hospital’s Centralized Institutional Review Board. Informed consent will be obtained from all subjects recruited to this dual parallel registry.
Case selection
Retrospective analysis of consecutive patients with dysfunctional AVF who underwent PCB and SCB angioplasty from May-2021 to February-2022 will be undertaken (Study 1). From March-2022, all new patients referred and treated with PCB and SCB will be subsequently included (Study 2). Informed consent will be obtained.
A total of 200 participants (100 participants in SCB-arm and 100 participants in PCB-arm) from SGH that fulfil the inclusion and exclusion criteria (Table 1) will be recruited. Participants will be followed-up for 12 months after the index intervention.
Table 1
Inclusion and Exclusion Criteria
Inclusion Criteria
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Exclusion Criteria
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Age 21–85 years
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Patient unable to provide informed consent
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Patient who requires balloon angioplasty for dysfunctional or thrombosed AVF
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Presence of symptomatic or angiographically significant central vein stenosis who require treatment, with more than 30% residual stenosis post angioplasty
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Matured AVF, defined as being in use for at least 1 month prior to angioplasty
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Patients who had underwent stent placement within the AVF circuit
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Successful thrombolysis and angioplasty of the underlying stenosis, defined as less than 30% residual stenosis on Digital Subtraction Angiography (DSA) based on visual assessment of the operator and restoration of thrill in the AVF on clinical examination. (For concurrent asymptomatic or angiographically not significant central vein stenosis, patients can be included if no treatment is required.)
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Patient who are currently enrolled in other DCB trials
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Received either PDCB or SDCB for the treatment of the stenosis
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Sepsis or active infection
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Recent intracranial bleed or gastrointestinal bleed within the past 12 months
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Allergy to iodinated contrast media, heparin, paclitaxel or sirolimus
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Pregnancy
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Inadequate treatment of underlying stenosis, defined as ≥ 30% residual stenosis of the underlying lesions.
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Investigational devices
Drug-coated balloon that will be used in this study consists of sirolimus drug-coated balloon (Selution Sustained Limus Release (SLR); M.A. MedAlliance SA, Nyon, Switzerland), with is coated with 1µg/mm2 of sirolimus and paclitaxel drug-coated balloon (Lutonix 035 DCB Catheter; Lutonix, Maple Grove, Minnesota), that is coated with 2µg/mm2 of paclitaxel.
Study procedure
All procedures will be performed in interventional suite equipped with fluoroscopy system according to center protocol by credentialled operators. Minimum diameter of each stenotic lesion will be determined pre-procedure.
Thrombosed AVF
Thrombosed AVF is treated with pharmaco-mechanical thrombolysis as per center protocol. Briefly, vascular sheaths or cannulas are placed in both antegrade and retrograde directions. Thrombolytic agents are then instilled. Through the sheath, a central venogram is performed followed by pull back venogram. Following that, balloon angioplasty and maceration of clots are performed. Once all stenoses are adequately treated (defined as ≤ 30% stenosis), the stenosis lesion will be treated with either SCB or PCB at the operator’s discretion or patients’ preference. Completion venograms are then obtained. The type and dose of the thrombolytic agent, administration of anti-coagulants, type, size, and length of balloon and thrombectomy devices used during the procedure are also at the operator’s discretion.
Non-thrombosed AVF
Initial angiogram will be performed via vascular sheaths, cannula, or angiographic catheter. All clinically significant stenosis will be treated with POBA. Should there be more than 1 stenosis, all the lesions will be labelled and treated (from the AV anastomosis up to, but not including, the subclavian vein). Lesions are considered separate if they are separated by a gap of at least 2 cm. The lesion will be dilated with POBA that is sized like the adjacent reference vessel. Inflation time will be at least 2 minutes per inflation. In the event of resistant stenosis, high-pressure conventional plain balloon or cutting balloon may also be used. In stenotic segment adjacent to aneurysmal segment, where percentage of stenosis is difficult to determine, the treated segment should reach at least 6mm in diameter.
Drug-coated balloon angioplasty
All the lesions will be treated with SCB or PCB that is sized like the adjacent reference vessel and will cover the geographical zone with at least 1cm proximal and distal overlap. The balloon will be inflated to an appropriate inflation pressure. Inflation time will be at least 2 minute per inflation. A final fistulogram will be obtained at the end of procedure.
Follow Up
The patients will be follow-up at 6- and 12-month after the intervention to assess the primary and secondary outcomes. Participants who are indicated for repeat intervention (Table 2) are considered to have reached primary endpoint.
Table 2
Indications of clinically significant lesions for repeat intervention
Indications
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1.Thrombosed or partially thrombosed AVF
2.Ipsilateral extremity edema
3.Alteration in pulse, thrill or bruit
4.Clinical features of inflow stenosis: lack of pulse augmentation
5.Clinical features of outflow stenosis: failure of fistula to collapse when the arm is elevated
6.Excessive collapse of venous segment upon arm elevation
7.New difficult in cannulation
8.Aspiration of clots
9.Inability to achieve the target dialysis blood flow
10.Prolonged bleeding beyond usual for 3 consecutive dialysis sessions
11.Unexplained (> 0.2 units) decreased in delivered Kt/V on a constant dialysis prescription
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Endpoints and definitions
Study’s primary and secondary endpoints are listed in Table 3.
Table 3
Primary and Secondary Endpoints
Primary Endpoint
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Secondary Endpoints
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Primary patency rate of the circuit at 6-month.
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Primary patency rate of the circuit at 12-month
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Treated lesion restenosis rate at 6- and 12-month (defined as incidence of stenosis > 50% diameter of adjacent reference vessel segment from angiography images)
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Number of repeat interventions to treated lesion at 6- and 12-months
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Number of repeat interventions to maintain access circuit (including interventions to treated lesion) at 6-and 12-months
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Treated lesion revascularisation free interval (defined as the interval from intervention to repeat clinically driven target lesion intervention)
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Complication rates of the procedure
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The patency outcomes are classified according to the Society of Interventional Radiology. [14] Postintervention primary patency is defined as interval following intervention until the next required intervention (angioplasty, thrombolysis, or surgical revision) or time of measurement of patency. Postintervention assisted primary patency is defined as interval after intervention until subsequent access thrombosis or time of measurement of patency. Secondary patency was defined as interval after intervention until the access is abandoned or time of measurement of patency.
Sample size calculation and statistical analysis
This is prospective and retrospective double arm registry study to compare the effectiveness of SCB against PCB angioplasty. From the results of PCB in published RCTs, the 6-month circuit patency was 58.3% while SCB results in 68% primary patency in our pilot study [10]. Based on Alpha of 0.05 and Beta of 0.2 and assuming a dropout rate of 10%, a sample size of 200 patients at 1:1 ratio has 80% power to detect a difference between the 2 group at 6 months.
The data analyses will be performed with STATA and SPSS version 23 by an independent biostatistician who will be blinded. Kaplan-Meier survival analyses will be used to estimate primary, assisted primary and secondary patency rates.