Intervention With Selution SLR™ Agent Balloon for Endovascular Latent Limus Therapy for Failing AV Fistulas (ISABELLA) Trial (ISABELLA)

September 23, 2021 updated by: Singapore General Hospital

The most common problem with haemodialysis arteriovenous fistulas (AVF) and arterio-venous grafts (AVG) is stenosis, which can lead to inadequate dialysis, and eventual access thrombosis. Conventional plain old balloon angioplasty (CBA) is associated with high recurrence rates of stenosis and repeated interventions. The advent of successful drug-eluting technology in the treatment of the coronary vascular bed and subsequent positive accumulating evidence in the peripheral arterial circulation has prompted the use of drug coated balloons (DCB) in the access fistula circuit for venous stenosis and in-stent restenosis. Recent studies suggest that DCBs may significantly reduce re-intervention rates on native and recurrent lesions. The restenosis process is in part or in whole the result of neo-intimal hyperplasia (NIH) and NIH is considered the main culprit in access circuit target lesion stenosis. NIH is the blood vessel's healing response to the barotrauma from the angioplasty process. A critical component of NIH is the cellular proliferative stage with mononuclear leucocytes identified as the primary inflammatory cell type involved. The rationale for drug elution is to block the NIH response with an anti-metabolite such as paclitaxel. It is important to emphasize that the role of drug elution in the treatment of vascular stenosis is not to obtain a good haemodynamic and luminal result but to preserve a good result obtained during POBA from later restenosis due to NIH and minimise reinterventions and readmissions to hospital for what is a frail population of patients.

A meta-analysis performed by Khawaja et al. seemed to suggest that DCBs conferred some benefit in terms of improving target lesion primary patency (TLPP) in AVFs. An updated meta-analysis performed by our own institution recently reinforced that DCB appears to be a better and safe alternative to CBA in treating patients with stenosis within all haemodialysis circuits (fistulas and grafts) based on 6- and 12-months primary patency and increased intervention free period 5. However, this was not reflected in the largest RCT to date of DCB vs CBA in AVF with no superior target lesion patency demonstrated at six months and one and two years follow-up. Another recent meta-analysis found paclitaxel-coated balloons (PCB) showed no statistically significant improvement over conventional balloons in decreasing fistula stenosis in randomized controlled trials but were significant for cohort studies. Hence this shows the heterogeneity of the available data in the literature and the result is dependent on what studies you include in the review. Another reason why the outcome data is variable is that the high-speed blood flow in dialysis access circuits washes a large amount of the paclitaxel away from the target lesion soon after application. A measurement in swine showed that only 20%-30% of paclitaxel was taken up into the coronary artery wall in vivo 15-25minutes after PCB application.

Furthermore, recent attention has been drawn to a possible increase in late mortality signal and lower amputation free survival in patients receiving DCB treatment with paclitaxel for peripheral arterial disease, although this suggestion has not been demonstrated in the data of DCB within the fistula circuit either at 1 or 2 years. In light of these concerns, attention has turned away recently from paclitaxel-based technologies to sirolimus coated platforms. Sirolimus, like paclitaxel, is a potent antiproliferative agent, which has been found to prevent restenosis in the coronary bed and more recently in the peripheral vasculature but to date has not been studied in AVF circuits The aims of the study is to determine the safety and efficacy of the MedAlliance SELUTION SLR 018™ DEB in the treatment of failing AV fistula due to conduit stenosis in patients undergoing renal dialysis.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Singapore
      • Singapore, Singapore, 169856
        • Singapore General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

40 patients with failing dialysis access treated with SELUTION SLR and meet inclusion/exclusion criteria will be enrolled for study

Description

Inclusion Criteria:

  • Patient aged ≥21 years and ≤90 years
  • Native AVF was created more than 2 months prior to the index procedure and had undergone 10 or more haemodialysis sessions utilising two needles
  • Target lesion location has to be located between the anastomoses to the auxiliary-subclavian vein junction, as defined by insertion of the cephalopods vein
  • On initial fistulogram, target lesion stenosis has to be >50% on angiographic assessment and in keeping with the clinical indicator for intervention
  • Stenosis had to be < 12cm in length (to allow for potential treatment with one DEB (length 15cm) only)
  • Stenosis had to be initially treated successfully with a high-pressure plain balloon prior to DEB treatment as defined by:- (A) No clinically significant dissection (flow limiting) (B) No extravasated requiring treatment/Stenting (C) Residual stenosis ≤30% by angiographic measurement (D) Ability to completely efface the lesion waist using the pre-dilation CBA
  • No more than one additional ("non-target") lesion in the access circuit that had to be also successfully treated (≤30% residual stenosis) before drug elation. Separate lesion was defined by at least 3cm in distance from the target lesion
  • Reference vessel diameters allowed are 4mm - 7mm

Exclusion Criteria:

  • Women who are pregnant, lactating or planning on becoming pregnant during study
  • Subject has more than two lesions in the access circuit
  • Subject had a secondary non-target lesion that could not be successfully treated
  • Sepsis or active infection
  • Asymptomatic target lesions
  • A thrombosis access or an access with thrombosis treated ≤30 days prior to the index procedure
  • Pseudoaneurysm in proposed target lesion area
  • Surgical revision of the access site performed, planned or expected ≤3 months before or after the index procedure
  • Patients who is taking immunosuppressive therapy or are routinely taking ≥15mg of prednisone per day
  • Currently participating in another investigational drug, biologic, or device study involving Sirolimus or Paclitaxel
  • Contraindication to aspirin or clopidogrel usage
  • Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, or language barrier such that the subject is unable to give informed consent.
  • Uncooperative attitude or potential for non-compliance with the requirements of the protocol making study participation impractical
  • Where final angioplasty treatment requires a stent or drug eluting balloon >8mm in diameter
  • Metastatic cancer or terminal medical condition
  • Blood coagulation disorders
  • Limited life expectancy (<12 months)
  • Allergy or other known contraindication to iodinated media contrast, heparin, or Sirolimus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Selution SLR™ 018 Drug Eluting Balloon
Subjects will undergo fistuloplasty with the study device - Selution SLR™ 018 Drug Eluting Balloon
Device: Selution SLR™ 018 Drug Eluting Balloon
Target lesion will be pre-dilated with high pressure non-compliant balloon, then treated with SELUTION SLR™ 018 DEB Balloon.
Other Names:
  • Sirolimus DEB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Target Lesion Primary Patency
Time Frame: 6 months post-index procedure
Defined as patency with no re-intervention to the area treated by SELUTION SLR™ DEB and a duplex-defined stenosis within the index-treated segment of <50%. TLPP ends when any of the following occur:- 1) clinically driven re-intervention to the treated segment, 2) thrombotic occlusions that includes the treatment segment, 3) surgical intervention that excludes the treatment segment from the access circuit, 4) abandonment of the AVF due to an inability to treat the target lesion, 5) duplex finding of more than 50% stenosis.
6 months post-index procedure
Freedom from adverse events
Time Frame: 30 days post-index procedure
Freedom from events including thrombosis, life-threatening events or those resulting in death, requiring hospitalisation, resulting in permanent disability, requiring intervention to prevent permanent impairment.
30 days post-index procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom from any serious adverse event(s) involving the AV access circuit or the patient
Time Frame: 3 and 6 months post-index procedure
3 and 6 months post-index procedure
Target Lesion Primary Patency and Access circuit primary patency
Time Frame: 3 months post index procedure
Defined as patency with no re-intervention to the area treated by SELUTION SLR™ DEB and a duplex-defined stenosis within the index-treated segment of <50%. TLPP ends when any of the following occur:- 1) clinically driven re-intervention to the treated segment, 2) thrombotic occlusions that includes the treatment segment, 3) surgical intervention that excludes the treatment segment from the access circuit, 4) abandonment of the AVF due to an inability to treat the target lesion, 5) duplex finding of more than 50% stenosis.
3 months post index procedure
Device Success
Time Frame: Intra-operative
Successful balloon inflation of the SELUTION catheter for more than 2 minutes and retrieval of the catheter
Intra-operative
Anatomical Success
Time Frame: Immediately post-op
<30% residual stenosis diameter measured immediately after an angioplasty
Immediately post-op
Clinical Success
Time Frame: 1 week post-index procedure
Improvement from baseline in the clinical or hemodynamic parameter (e.g. blood flow, venous pressure) that was the initial indicator of fistula dysfunction and the resumption of normal hemodialysis for a minimum of at least 1 session following the procedure
1 week post-index procedure
Need for open revision surgery
Time Frame: 2 years post-index procedure
2 years post-index procedure
Secondary patency
Time Frame: 3 months and 6 months post-index procedure
Interval after intervention until access circuit is abandoned, including reinterventions to reestablish access flow.
3 months and 6 months post-index procedure
Access circuit thrombosis
Time Frame: 2 years post-index procedure
2 years post-index procedure
Number of interventions required to maintain access circuit patency
Time Frame: 3 and 6 months post-index procedure
3 and 6 months post-index procedure
Mortality rate
Time Frame: 3 and 6 months post-index procedure
3 and 6 months post-index procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Singapore General Hospital

Investigators

  • Principal Investigator: Tze Tec Chong, Singapore General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2020

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

October 30, 2023

Study Registration Dates

First Submitted

November 8, 2020

First Submitted That Met QC Criteria

November 12, 2020

First Posted (Actual)

November 16, 2020

Study Record Updates

Last Update Posted (Actual)

September 27, 2021

Last Update Submitted That Met QC Criteria

September 23, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020/2782

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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