<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04409912</url>
  </required_header>
  <id_info>
    <org_study_id>2019/2896</org_study_id>
    <nct_id>NCT04409912</nct_id>
  </id_info>
  <brief_title>Sirolimus Coated Angioplasty Versus Plain Balloon Angioplasty</brief_title>
  <acronym>IMPRESSION</acronym>
  <official_title>SIroliMus Coated angioPlasty Versus Plain Balloon Angioplasty in the tREatment of dialySis acceSs dysfunctION (IMPRESSION)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sengkang General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Singapore General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A functioning dialysis access is critical to the delivery of hemodialysis therapy in patients&#xD;
      with End Stage Renal Disease. Stenosis secondary to neo-intimal hyperplasia frequently occur&#xD;
      within the dialysis access, resulting in dysfunction. Conventional balloon angioplasty is the&#xD;
      current standard of care for treatment of stenosis but is associated with high rate of&#xD;
      recurrence. Paclitaxel coated balloon has been shown to be superior to conventional balloon&#xD;
      angioplasty in dialysis access interventions but recent meta-analysis has shown an increase&#xD;
      in mortality when paclitaxel coated balloon and stents are used in lower limb angioplasty.&#xD;
      Sirolimus coated angioplasty balloon are second generation drug coated balloon that have been&#xD;
      shown to be effective in coronary artery interventions. Sirolimus is cytostatic in nature&#xD;
      with good safety profile. In our pilot study, sirolimus coated balloon has been shown to be&#xD;
      safe and effective in the salvaged of thrombosed arteriovenous graft. Therefore, the&#xD;
      investigators are conducting a double-blinded, multi-center randomised control trial to&#xD;
      compare the 6 month patency of arteriovenous fistula after intervention with sirolimus coated&#xD;
      balloon versus conventional balloon angioplasty.&#xD;
&#xD;
      The investigators hypothesise that the addition of SCB after successful balloon angioplasty&#xD;
      with conventional plain balloon is superior to conventional plain balloon angioplasty alone&#xD;
      with decreased restenosis of the treated lesion, improved access circuit and treated lesion&#xD;
      patency, and decreased number of interventions needed to maintain patency.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dialysis vascular accesses such as Arteriovenous Fistula (AVF) and Arteriovenous Grafts (AVG)&#xD;
      are surgically created vasculatures used for hemodialysis in patients with End-Stage Renal&#xD;
      Disease (ESRD). A functioning dialysis vascular access is critical to the delivery of&#xD;
      life-saving hemodialysis (HD) treatment to these patients. Unfortunately, neointimal&#xD;
      hyperplasia frequently occurs within the dialysis vascular access, resulting in stenosis,&#xD;
      poor flow and thrombosis with loss of function. The durability of both AVF and AVG are poor,&#xD;
      with an almost 50% failure rate after a median lifetime of 3 to 7 years for AVF and 12 to 18&#xD;
      months for AVG. Vascular access failure is the most common reason for hospitalization among&#xD;
      HD patients. The global healthcare costs for treating vascular access-related complications&#xD;
      amount to USD 18 billion, and in USD 1 billion in the US alone. These figures are set to&#xD;
      increase, due to the increase in the prevalence of access interventions and hemodialysis&#xD;
      patients globally. Singapore has one of the highest ESRD rates in the world and the&#xD;
      investigators are facing an increasing number of patients with ESRD and the majority of the&#xD;
      patients opting for hemodialysis as their treatment modality. As such, vascular&#xD;
      access-related complication is set to be a major contribution of healthcare cost in our&#xD;
      nation.&#xD;
&#xD;
      The current gold standard therapy for the treatment of stenosis in dialysis access is plain&#xD;
      balloon angioplasty (BA). Despite its widespread availability and minimally invasive nature,&#xD;
      the mid- and long-term patency with BA in patients with ESRD is poor. The reported average&#xD;
      primary patency after BA is around 40-50% at 1 year. Multiple repeated angioplasty is&#xD;
      required to maintain the patency of the vascular access. Hence, there is an urgent clinical&#xD;
      need to improve the patency of dialysis vascular access.&#xD;
&#xD;
      Recently, the use of stents, in particular stent graft, has been shown to be superior to&#xD;
      angioplasty for stenosis occurring at the site of venous anastomoses of an AVG. The incidence&#xD;
      of patency of the treatment area was significantly greater in the stent-graft group than in&#xD;
      the balloon-angioplasty group (51% vs. 23%, P&lt;0.001), as was the incidence of patency of the&#xD;
      access circuit (38% vs. 20%, P=0.008) at 6 months. For cephalic arch stenosis in AVF, the use&#xD;
      of stent graft has also been shown to be superior to bare metal stent. The 6 month primary&#xD;
      patency for stent graft and bare stent was 81.8 and 39.1%, respectively. One-year primary&#xD;
      patency for stent graft and bare stent was 31.8 and 0.00%, respectively (P = 0.002). However,&#xD;
      the use of stent graft for the management of dialysis vascular access is not without any&#xD;
      concern. In particular, re-stenosis can occur within the stented segment (post stent 12-month&#xD;
      primary patency is 46%), resulting in the need for repeat angioplasty. Future stent&#xD;
      deployment in the re-stenotic segment may also not be feasible due to the presence of the&#xD;
      stent. Moreover, the presence of a stent can impede future surgical revision or new access&#xD;
      creation within the same vessel.&#xD;
&#xD;
      Paclitaxel-coated balloon angioplasty (PCBA) has also been shown recently to be superior to&#xD;
      plain BA in the treatment of stenosis in dialysis vascular access. This is because the very&#xD;
      intervention used to treat the underlying stenosis by plain BA can induce vascular injury and&#xD;
      accelerate intimal hyperplasia, resulting in rapid restenosis and the need for repeated&#xD;
      procedures to maintain vessel patency. By releasing Paclitaxel, which is an&#xD;
      anti-proliferative drug, locally into the vessel wall during balloon contact, it will blunt&#xD;
      the acceleration of intimal hyperplasia response, resulting in improved primary patency after&#xD;
      angioplasty. Additionally, unlike stents, PCBA does not leave a permanent structure that may&#xD;
      impede future surgical revision. In a small 40 patient pilot study, the primary unassisted&#xD;
      patency in the PCBA group was significantly better than the plain BA group at 6 (70 % versus&#xD;
      25 %) and 12 months (35 % versus 5 %, p &lt;0.001) respectively. Recent randomized control&#xD;
      trials have also shown the superiority of PCBA over plain balloon angioplasty in the&#xD;
      treatment of stenosis in dialysis vascular access. However, concerns had also arisen recently&#xD;
      in the use of PCBA. In large lower limb studies involving the use of PCBA, meta-analysis had&#xD;
      revealed an increased risk of death in patients that are treated with PCBA or&#xD;
      paclitaxel-coated stent. This had led to warning from the United States Food and Drug&#xD;
      Administration (FDA) and the issue of guidelines from the interventional societies&#xD;
&#xD;
      Sirolimus coated balloon (SCB) is the new generation of drug-eluting balloons available in&#xD;
      the market. Compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high&#xD;
      margin of safety. It has a high transfer rate to the vessel wall and effectively inhibits&#xD;
      neointimal hyperplasia in the porcine coronary model. In the coronary artery interventions,&#xD;
      preliminary clinical studies using SCB have also shown excellent procedural and 6-month&#xD;
      patency.&#xD;
&#xD;
      The effectiveness of SCB in patients with dialysis access dysfunction has been shown in a&#xD;
      small pilot study in the salvage of thrombosed AVG and investigators postulate that SCB will&#xD;
      be a viable option in patients who requires treatment with drug-coated balloon.&#xD;
&#xD;
      The investigators aim to conduct a multicenter double-blinded randomized controlled trial to&#xD;
      compare the 6 month unassisted patency rate of SCB angioplasty versus plain balloon&#xD;
      angioplasty in the management of stenosis in arteriovenous fistula.&#xD;
&#xD;
      RECRUITMENT:&#xD;
&#xD;
      Patients with matured AVF (in use for more than 1 month) that are dysfunctional and are&#xD;
      already scheduled to undergo balloon angioplasty will be considered for the trial. Patients&#xD;
      will be consented if they fulfill the preliminary eligibility criteria and are agreeable to&#xD;
      participate in the study. Once all the eligibility criteria are fulfilled, including&#xD;
      angiographic criteria assessed on the day of the procedure, the patient is entered into the&#xD;
      trial and randomised. Patients who are unsuitable for the trial will be treated in the&#xD;
      conventional way with PB and considered as screen failure.&#xD;
&#xD;
      STUDY PROCEDURE:&#xD;
&#xD;
      The AVF will be assessed with ultrasound for possible access sites. All patients will undergo&#xD;
      a fistulogram which is obtained by injection of contrast. The access site will be left to the&#xD;
      discretion of the procedurist. The fistulogram should include the entire dialysis circuit&#xD;
      from the arteriovenous anastomosis to the central veins. The suggested approach would include&#xD;
      a fistulogram via an 18 Gauge cannula inserted into the arterialised vein. When there is no&#xD;
      spontaneous reflux of contrast into the artery, reflux opacification of the arteriovenous&#xD;
      (AV) anastomosis is achieved by injecting contrast during inflation of a blood pressure cuff&#xD;
      or a tourniquet around the arm. Alternatively, a trans-radial or arterial approach may be&#xD;
      used to obtain the fistulogram&#xD;
&#xD;
      Based on fistulogram findings, the access site will be placed up to the discretion of the&#xD;
      procedurist. If an 18G cannula is used, it may be exchanged for a vascular sheath that is&#xD;
      sized appropriately based on the planned balloon sizes). Alternatively, the 18G cannula may&#xD;
      be removed and a new access site for intervention may be chosen. A new puncture will be&#xD;
      performed with the insertion of a vascular sheath (sized appropriately according to planned&#xD;
      balloon sizes). Two access sites (both antegrade and retrograde) may be needed in certain&#xD;
      cases. A trans-radial or arterial approach may also be considered if necessary&#xD;
&#xD;
      In the event that opacification of the anastomosis was not earlier achieved even with&#xD;
      inflation of a blood pressure cuff around the arm, it will be performed via contrast&#xD;
      injection through a catheter in the feeding artery.&#xD;
&#xD;
      When there is more than 1 stenosis, all the lesions will be labelled and treated with&#xD;
      conventional balloon angioplasty (from the AV anastomosis up to, but not including, the&#xD;
      subclavian vein). Lesions are considered separate if they are separated by a gap of at least&#xD;
      2 cm. The lesion or lesions will be dilated with standard angioplasty that is sized similar&#xD;
      to the adjacent reference vessel. Inflation time will be at least 1 minute per inflation. The&#xD;
      balloon will be inflated to an appropriate inflation pressure as per institution standardised&#xD;
      practice to achieve &lt;30% residual stenosis and satisfactory thrill. If there is significant&#xD;
      residual stenosis after angioplasty (defined as &gt; 30% stenosis), repeat angioplasty with the&#xD;
      same standard angioplasty balloon or a larger standard angioplasty balloon may be used at&#xD;
      operator's discretion. High-pressure angioplasty balloon or cutting balloon may also be used,&#xD;
      if necessary, in the event of resistant stenosis. In stenotic segment adjacent to aneurysmal&#xD;
      segment, where the percentage of stenosis is difficult to determine, the treated segment&#xD;
      should reach at least reach 6mm.&#xD;
&#xD;
      Randomisation occurs when all the lesions are treated adequately, defined as less than 30%&#xD;
      residual stenosis after standard treatment.&#xD;
&#xD;
      Patients will be randomised to receive either the sirolimus coated balloon or plain balloon.&#xD;
      Repeated angioplasty of the stenotic segments that were successfully treated (defined as less&#xD;
      than 30% residual stenosis) will be performed using sirolimus coated balloon (for patient&#xD;
      randomised into the sirolimus balloon arm) or plain/placebo balloon (for patients randomised&#xD;
      into the placebo arm)&#xD;
&#xD;
      POST-PROCEDURE ULTRASOUND SCAN:&#xD;
&#xD;
      All participants will receive an ultrasound scan of their AVF after their procedure before&#xD;
      discharge. The diameter of the vessel at the treated sites will be measured and documented.&#xD;
      Brachial artery flow and flow within the outflow vein will also be measured and documented&#xD;
&#xD;
      * Patency definitions are defined based on SIR reporting standards (Gray et al., 2003):&#xD;
&#xD;
      Post-intervention target lesion patency:&#xD;
&#xD;
      Interval after intervention until the next re-intervention at or adjacent to the original&#xD;
      treatment site or until the access is abandoned. Percutaneous or surgical treatments of a new&#xD;
      arterial or venous outflow stenosis/occlusion (including access thrombosis) that do not&#xD;
      involve or exclude the original lesion from the access circuit are compatible with lesion&#xD;
      patency. The creation of new access that incorporates the target lesion into the new access&#xD;
      circuit is also compatible with target lesion patency.&#xD;
&#xD;
      Post-intervention access circuit primary patency:&#xD;
&#xD;
      Interval following intervention until the next access thrombosis or repeated intervention. It&#xD;
      ends with the treatment of a lesion anywhere within the access circuit, from the arterial&#xD;
      inflow to the superior vena cava-right atrial junction.&#xD;
&#xD;
      Post-intervention access circuit assisted primary patency:&#xD;
&#xD;
      Interval after intervention until access thrombosis or surgical intervention that excludes&#xD;
      the treated lesion from the access circuit. Percutaneous treatments of either&#xD;
      restenosis/occlusion of the previously treated lesion or a new arterial or venous outflow&#xD;
      stenosis/occlusion (excluding access thrombosis) are compatible with assisted primary&#xD;
      patency.&#xD;
&#xD;
      Post-intervention access circuit secondary patency:&#xD;
&#xD;
      Interval after intervention until the access is surgically declotted, revised or abandoned.&#xD;
      Thrombolysis and percutaneous thrombectomy are compatible with secondary patency.&#xD;
&#xD;
      ^Complications will be categorised according to SIR definitions of minor or major&#xD;
      complications (Aruny et al., 2003):&#xD;
&#xD;
      A major complication is defined as one that:&#xD;
&#xD;
        1. require therapy, minor hospitalisation (&lt; 48 hours),&#xD;
&#xD;
        2. require major therapy, unplanned increase in the level of care, prolonged&#xD;
           hospitalisation (&gt;48 hours),&#xD;
&#xD;
        3. leads to permanent adverse sequelae, or&#xD;
&#xD;
        4. death&#xD;
&#xD;
      A minor complication is one that:&#xD;
&#xD;
        1. requires no therapy with no consequence,&#xD;
&#xD;
        2. requires nominal therapy with no consequence; includes overnight admission for&#xD;
           observation only.&#xD;
&#xD;
      POST-PROCEDURE FOLLOW-UP ULTRASOUND SCAN OF AVF:&#xD;
&#xD;
      Patients will be followed-up at:&#xD;
&#xD;
      3 months (± 1 weeks): assessment of primary outcome 6 months (± 4 weeks): assess the target&#xD;
      lesion and access circuit. 12 months (± 4 weeks): assess AVF patency and study closure&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 11, 2021</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be randomly allocated in a 1:1 ratio into either the treatment (SCB) arm or control (PB) arm. As above-elbow AVFs generally have larger vessel size and better outcomes compared to below-elbow AVFs, randomisation will be stratified by location of AVF (above vs below elbow) to ensure a more even distribution of AVF by location between both groups.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Dialysis centre staff and procedurist performing the intervention will also be masked</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Primary patency of the AVF at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>This is measured by the percentage of patients whose AVF remain patent at 6 months after the procedure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time taken to the next intervention</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>The number of months from procedure to the next interventions. This will be track until study completion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treated lesion percent stenosis at 6 and 12 month ultrasound</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>Defined as percent stenosis relative to adjacent reference vessel, [1 - (minimum lesion diameter / reference vessel diameter)] x 100)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treated lesion re-stenosis rate at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Defined as incidence of stenosis &gt; 50% diameter of adjacent reference vessel segment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of repeat interventions to treated lesion at 6 and 12 months</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>How many repeat interventions to treated lesion at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of repeat interventions to maintain access circuit (including interventions to treated lesion) at 6 and 12 months</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>How many repeat interventions to maintain access circuit (including interventions to treated lesion) at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treated lesion revascularisation free interval</measure>
    <time_frame>anytime within 12 months study participation</time_frame>
    <description>Defined as the interval from intervention to repeat clinically driven target lesion intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>De nova stenosis detected on ultrasound scan at 3, 6 and 12 months</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Presence of De nova stenosis detected on ultrasound scan at 3, 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post intervention treated lesion patency at 3, 6 and 12 months</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Percentage of patients whose treated stenosis remains patent at 3, 6, and 12 months after the procedure. This is determined by the use of ultrasound imaging or angiogram or clinical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-intervention primary patency at 3, 6 and 12 months</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Percentage of patients whose AVF remains patent and does not require any further interventions at 3, 6, and 12 months after the procedure. This is determined by the use of ultrasound imaging or angiogram or clinical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-intervention assisted primary patency at 3, 6 and 12 months</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Percentage of patients whose AVF requires additional interventions to remains patent at 3, 6, and 12 months after the procedure. This is determined by clinical history during the study period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-intervention secondary patency at 3, 6 and 12 months</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Percentage of patients whose AVF has thrombosed and required additional procedure to restore flow at 3, 6, and 12 months after the procedure. This is determined by clinical history during the study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complication rates at 1, 3, 6 and 12 months</measure>
    <time_frame>1, 3 6 and 12 months</time_frame>
    <description>Complication rates at 1, 3, 6 and 12 months</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>End Stage Renal Failure on Dialysis</condition>
  <condition>Arteriovenous Graft Occlusion</condition>
  <arm_group>
    <arm_group_label>Sirolimus coated balloon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The trial product is MagicTouch sirolimus drug coated balloon (Concept Medical). Sirolimus will be transferred from the balloon to the vessel wall by inflating the sirolimus coated balloons at 2 minutes at rated burst pressure (typically 12 to 14ATM). All the lesions within the dialysis circuit with sirolimus coated balloon.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plain balloon</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The plain balloon or placebo will not be coated. The plain balloon will be inflated at 2 minutes at rated burst pressure (typically 12 to 14 ATM). Plain balloon will be applied to all the narrowed segment of the dialysis circuit</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sirolimus coated balloon</intervention_name>
    <description>Sirolimus has a high transfer rate to the vessel wall and effectively inhibit neointimal hyperplasia in the porcine coronary model. In coronary artery interventions, preliminary clinical studies using sirolimus coated balloon have shown excellent procedural and 6 month patency. The effectiveness of sirolimus coated balloon in patients with dialysis access dysfunction has been shown in a small pilot study in the salvage of thrombosed arteriovenous graft.&#xD;
When compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high margin of safety.</description>
    <arm_group_label>Sirolimus coated balloon</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Plain balloon</intervention_name>
    <description>Plain balloon angioplasty is the current standard therapy to treat stenosis in dialysis access. However, the mid and long term patency of plain balloon angioplasty in patients with end stage renal disease is poor. The average primary patency is around 40 to 50 percent at 1 year and multiple repeated angioplasty is required to maintain the patency of the vascular access.</description>
    <arm_group_label>Plain balloon</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 21 to 85 years&#xD;
&#xD;
          2. Patient who requires balloon angioplasty for dysfunction arteriovenous fistula&#xD;
&#xD;
          3. Matured AVF, defined as being in use for at least 1 month prior to angioplasty&#xD;
&#xD;
          4. 4. Successful angioplasty of the underlying stenosis, defined as less than 30%&#xD;
             residual stenosis on Digital Subtraction Angiography (DSA) based on visual assessment&#xD;
             of the operator and restoration of thrill in the AVF on clinical examination. (For&#xD;
             concurrent asymptomatic or angiographically not significant central vein stenosis,&#xD;
             patients can be included if no treatment is required.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient unable to provide informed consent&#xD;
&#xD;
          2. Thrombosed or partially thrombosed AVF&#xD;
&#xD;
          3. Presence of symptomatic or angiographically significant central vein stenosis who&#xD;
             require treatment, with more than 30% residual stenosis post angioplasty&#xD;
&#xD;
          4. Patients who had underwent stent placement within the AVF circuit&#xD;
&#xD;
          5. Patient who are currently enrolled in other drug eluting balloon trials&#xD;
&#xD;
          6. Sepsis or active infection&#xD;
&#xD;
          7. Recent intracranial bleed or gastrointestinal bleed within the past 12 months&#xD;
&#xD;
          8. Allergy to iodinated contrast media, anti-platelet drugs, heparin or sirolimus&#xD;
&#xD;
          9. Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chieh Suai Tan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chieh Suai Tan, MD</last_name>
    <phone>+6581231127</phone>
    <email>tan.chieh.suai@singhealth.com.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jackie Pei Ho, MD</last_name>
      <email>surhp@nus.edu.sg</email>
    </contact>
    <investigator>
      <last_name>Jackie Pei Ho, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rajesh Babu Dharmaraj, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jun Jie Ng, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julian Chi Leung Wong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anil Gopinathan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stanley Eu Kuang Loh, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shao Jin Ong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gary Yoong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xinquan Chen</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chieh Suai Tan, MD</last_name>
      <email>tan.chieh.suai@singhealth.com.sg</email>
    </contact>
    <investigator>
      <last_name>Chieh Suai Tan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ru Yu Tan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Suh Chien Pang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alvin Ren Kwang Tng, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kiang Hiong Tay, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Luke Han Wei Toh, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shaun Xavier Ju Min Chan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jasmine Ming Er Chua, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Apoorva Gogna, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Farah Gillan Irani, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pradesh Kumar Kutty Krishnan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kristen Alexa Lee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sum Leong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Richard Hoau Gong Lo, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ankur Patel, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bien Soo Tan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chow Wei Too, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kun Da Zhuang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tze Tec Chong, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Siew Ping Chng, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tjun Yip Tang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hsien Ts'ung Tay, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Hao Yun Yap, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chee Wooi Tan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nanda Kumar Karaddi Venkatanarasimha, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sivanathan Chandramohan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sonam Tashi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alfred Bingchao Tan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexander Sheng Ming Tan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mark Qi Wei Wang, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sengkang General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>544886</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edward Tieng Chek Choke, MD</last_name>
      <email>edward.choke.t.c@singhealth.com.sg</email>
    </contact>
    <investigator>
      <last_name>Edward Tieng Chek Choke, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jia Sheng Tay, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Roy-Chaudhury P, Sukhatme VP, Cheung AK. Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint. J Am Soc Nephrol. 2006 Apr;17(4):1112-27. doi: 10.1681/ASN.2005050615.</citation>
    <PMID>16565259</PMID>
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  <reference>
    <citation>Lee T, Roy-Chaudhury P. Advances and new frontiers in the pathophysiology of venous neointimal hyperplasia and dialysis access stenosis. Adv Chronic Kidney Dis. 2009 Sep;16(5):329-38. doi: 10.1053/j.ackd.2009.06.009.</citation>
    <PMID>19695501</PMID>
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    <citation>Pantelias K, Grapsa E. Vascular access today. World J Nephrol. 2012 Jun 6;1(3):69-78. doi: 10.5527/wjn.v1.i3.69.</citation>
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    <citation>Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, Chen JT, Cope E, Gipson D, He K, Herman W, Heung M, Hirth RA, Jacobsen SS, Kalantar-Zadeh K, Kovesdy CP, Leichtman AB, Lu Y, Molnar MZ, Morgenstern H, Nallamothu B, O'Hare AM, Pisoni R, Plattner B, Port FK, Rao P, Rhee CM, Schaubel DE, Selewski DT, Shahinian V, Sim JJ, Song P, Streja E, Kurella Tamura M, Tentori F, Eggers PW, Agodoa LY, Abbott KC. US Renal Data System 2014 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2015 Jul;66(1 Suppl 1):Svii, S1-305. doi: 10.1053/j.ajkd.2015.05.001. No abstract available. Erratum In: Am J Kidney Dis. 2015 Sep;66(3):545. Am J Kidney Dis. 2015 Sep;66(3):545.</citation>
    <PMID>26111994</PMID>
  </reference>
  <reference>
    <citation>Office NRoD: Trends in Chronic Kidney Failure Stage 5 in Singapore 2012 / 2013. In.</citation>
  </reference>
  <reference>
    <citation>Rajan DK, Bunston S, Misra S, Pinto R, Lok CE. Dysfunctional autogenous hemodialysis fistulas: outcomes after angioplasty--are there clinical predictors of patency? Radiology. 2004 Aug;232(2):508-15. doi: 10.1148/radiol.2322030714.</citation>
    <PMID>15286321</PMID>
  </reference>
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    <citation>Manninen HI, Kaukanen ET, Ikaheimo R, Karhapaa P, Lahtinen T, Matsi P, Lampainen E. Brachial arterial access: endovascular treatment of failing Brescia-Cimino hemodialysis fistulas--initial success and long-term results. Radiology. 2001 Mar;218(3):711-8. doi: 10.1148/radiology.218.3.r01mr38711.</citation>
    <PMID>11230644</PMID>
  </reference>
  <reference>
    <citation>Heye S, Maleux G, Vaninbroukx J, Claes K, Kuypers D, Oyen R. Factors influencing technical success and outcome of percutaneous balloon angioplasty in de novo native hemodialysis arteriovenous fistulas. Eur J Radiol. 2012 Sep;81(9):2298-303. doi: 10.1016/j.ejrad.2011.09.004. Epub 2011 Sep 28.</citation>
    <PMID>21955605</PMID>
  </reference>
  <reference>
    <citation>Haskal ZJ, Trerotola S, Dolmatch B, Schuman E, Altman S, Mietling S, Berman S, McLennan G, Trimmer C, Ross J, Vesely T. Stent graft versus balloon angioplasty for failing dialysis-access grafts. N Engl J Med. 2010 Feb 11;362(6):494-503. doi: 10.1056/NEJMoa0902045.</citation>
    <PMID>20147715</PMID>
  </reference>
  <reference>
    <citation>Shemesh D, Goldin I, Zaghal I, Berlowitz D, Raveh D, Olsha O. Angioplasty with stent graft versus bare stent for recurrent cephalic arch stenosis in autogenous arteriovenous access for hemodialysis: a prospective randomized clinical trial. J Vasc Surg. 2008 Dec;48(6):1524-31, 1531.e1-2. doi: 10.1016/j.jvs.2008.07.071. Epub 2008 Oct 1.</citation>
    <PMID>18829240</PMID>
  </reference>
  <reference>
    <citation>Salman L, Asif A. Stent graft for nephrologists: concerns and consensus. Clin J Am Soc Nephrol. 2010 Jul;5(7):1347-52. doi: 10.2215/CJN.02380310. Epub 2010 May 27.</citation>
    <PMID>20507955</PMID>
  </reference>
  <reference>
    <citation>Allon M. Current management of vascular access. Clin J Am Soc Nephrol. 2007 Jul;2(4):786-800. doi: 10.2215/CJN.00860207. Epub 2007 May 30.</citation>
    <PMID>17699495</PMID>
  </reference>
  <reference>
    <citation>Katsanos K, Karnabatidis D, Kitrou P, Spiliopoulos S, Christeas N, Siablis D. Paclitaxel-coated balloon angioplasty vs. plain balloon dilation for the treatment of failing dialysis access: 6-month interim results from a prospective randomized controlled trial. J Endovasc Ther. 2012 Apr;19(2):263-72. doi: 10.1583/11-3690.1.</citation>
    <PMID>22545894</PMID>
  </reference>
  <reference>
    <citation>Kennedy SA, Mafeld S, Baerlocher MO, Jaberi A, Rajan DK. Drug-Coated Balloon Angioplasty in Hemodialysis Circuits: A Systematic Review and Meta-Analysis. J Vasc Interv Radiol. 2019 Apr;30(4):483-494.e1. doi: 10.1016/j.jvir.2019.01.012. Epub 2019 Mar 8.</citation>
    <PMID>30857987</PMID>
  </reference>
  <reference>
    <citation>Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2018 Dec 18;7(24):e011245. doi: 10.1161/JAHA.118.011245.</citation>
    <PMID>30561254</PMID>
  </reference>
  <reference>
    <citation>Updated CIRSE Position Statement on the use of paclitaxel-coated balloons and stents in peripheral arterial disease.https://www.cirse.org/research/current-updates/</citation>
  </reference>
  <reference>
    <citation>UPDATE: Treatment of Peripheral Arterial Disease with Paclitaxel-Coated Balloons and Paclitaxel-Eluting Stents Potentially Associated with Increased Mortality - Letter to Health Care Providers. https://www.fda.gov/medical-devices/letters-health-care-providers/update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel-eluting</citation>
  </reference>
  <reference>
    <citation>Clever YP, Peters D, Calisse J, Bettink S, Berg MC, Sperling C, Stoever M, Cremers B, Kelsch B, Bohm M, Speck U, Scheller B. Novel Sirolimus-Coated Balloon Catheter: In Vivo Evaluation in a Porcine Coronary Model. Circ Cardiovasc Interv. 2016 Apr;9(4):e003543. doi: 10.1161/CIRCINTERVENTIONS.115.003543.</citation>
    <PMID>27069105</PMID>
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  <reference>
    <citation>Verheye S, Vrolix M, Kumsars I, Erglis A, Sondore D, Agostoni P, Cornelis K, Janssens L, Maeng M, Slagboom T, Amoroso G, Jensen LO, Granada JF, Stella P. The SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis): Angiographic Results and 1-Year Clinical Outcomes. JACC Cardiovasc Interv. 2017 Oct 23;10(20):2029-2037. doi: 10.1016/j.jcin.2017.06.021. Epub 2017 Sep 27.</citation>
    <PMID>28964764</PMID>
  </reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>April 24, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04409912
org study id: 2019/2896
nct id: NCT04409912
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A functioning dialysis access is critical to the delivery of hemodialysis therapy in patients
      with End Stage Renal Disease. Stenosis secondary to neo-intimal hyperplasia frequently occur
      within the dialysis access, resulting in dysfunction. Conventional balloon angioplasty is the
      current standard of care for treatment of stenosis but is associated with high rate of
      recurrence. Paclitaxel coated balloon has been shown to be superior to conventional balloon
      angioplasty in dialysis access interventions but recent meta-analysis has shown an increase
      in mortality when paclitaxel coated balloon and stents are used in lower limb angioplasty.
      Sirolimus coated angioplasty balloon are second generation drug coated balloon that have been
      shown to be effective in coronary artery interventions. Sirolimus is cytostatic in nature
      with good safety profile. In our pilot study, sirolimus coated balloon has been shown to be
      safe and effective in the salvaged of thrombosed arteriovenous graft. Therefore, the
      investigators are conducting a double-blinded, multi-center randomised control trial to
      compare the 6 month patency of arteriovenous fistula after intervention with sirolimus coated
      balloon versus conventional balloon angioplasty.

      The investigators hypothesise that the addition of SCB after successful balloon angioplasty
      with conventional plain balloon is superior to conventional plain balloon angioplasty alone
      with decreased restenosis of the treated lesion, improved access circuit and treated lesion
      patency, and decreased number of interventions needed to maintain patency.
Dialysis vascular accesses such as Arteriovenous Fistula (AVF) and Arteriovenous Grafts (AVG)
      are surgically created vasculatures used for hemodialysis in patients with End-Stage Renal
      Disease (ESRD). A functioning dialysis vascular access is critical to the delivery of
      life-saving hemodialysis (HD) treatment to these patients. Unfortunately, neointimal
      hyperplasia frequently occurs within the dialysis vascular access, resulting in stenosis,
      poor flow and thrombosis with loss of function. The durability of both AVF and AVG are poor,
      with an almost 50% failure rate after a median lifetime of 3 to 7 years for AVF and 12 to 18
      months for AVG. Vascular access failure is the most common reason for hospitalization among
      HD patients. The global healthcare costs for treating vascular access-related complications
      amount to USD 18 billion, and in USD 1 billion in the US alone. These figures are set to
      increase, due to the increase in the prevalence of access interventions and hemodialysis
      patients globally. Singapore has one of the highest ESRD rates in the world and the
      investigators are facing an increasing number of patients with ESRD and the majority of the
      patients opting for hemodialysis as their treatment modality. As such, vascular
      access-related complication is set to be a major contribution of healthcare cost in our
      nation.

      The current gold standard therapy for the treatment of stenosis in dialysis access is plain
      balloon angioplasty (BA). Despite its widespread availability and minimally invasive nature,
      the mid- and long-term patency with BA in patients with ESRD is poor. The reported average
      primary patency after BA is around 40-50% at 1 year. Multiple repeated angioplasty is
      required to maintain the patency of the vascular access. Hence, there is an urgent clinical
      need to improve the patency of dialysis vascular access.

      Recently, the use of stents, in particular stent graft, has been shown to be superior to
      angioplasty for stenosis occurring at the site of venous anastomoses of an AVG. The incidence
      of patency of the treatment area was significantly greater in the stent-graft group than in
      the balloon-angioplasty group (51% vs. 23%, P<0.001), as was the incidence of patency of the
      access circuit (38% vs. 20%, P=0.008) at 6 months. For cephalic arch stenosis in AVF, the use
      of stent graft has also been shown to be superior to bare metal stent. The 6 month primary
      patency for stent graft and bare stent was 81.8 and 39.1%, respectively. One-year primary
      patency for stent graft and bare stent was 31.8 and 0.00%, respectively (P = 0.002). However,
      the use of stent graft for the management of dialysis vascular access is not without any
      concern. In particular, re-stenosis can occur within the stented segment (post stent 12-month
      primary patency is 46%), resulting in the need for repeat angioplasty. Future stent
      deployment in the re-stenotic segment may also not be feasible due to the presence of the
      stent. Moreover, the presence of a stent can impede future surgical revision or new access
      creation within the same vessel.

      Paclitaxel-coated balloon angioplasty (PCBA) has also been shown recently to be superior to
      plain BA in the treatment of stenosis in dialysis vascular access. This is because the very
      intervention used to treat the underlying stenosis by plain BA can induce vascular injury and
      accelerate intimal hyperplasia, resulting in rapid restenosis and the need for repeated
      procedures to maintain vessel patency. By releasing Paclitaxel, which is an
      anti-proliferative drug, locally into the vessel wall during balloon contact, it will blunt
      the acceleration of intimal hyperplasia response, resulting in improved primary patency after
      angioplasty. Additionally, unlike stents, PCBA does not leave a permanent structure that may
      impede future surgical revision. In a small 40 patient pilot study, the primary unassisted
      patency in the PCBA group was significantly better than the plain BA group at 6 (70 % versus
      25 %) and 12 months (35 % versus 5 %, p <0.001) respectively. Recent randomized control
      trials have also shown the superiority of PCBA over plain balloon angioplasty in the
      treatment of stenosis in dialysis vascular access. However, concerns had also arisen recently
      in the use of PCBA. In large lower limb studies involving the use of PCBA, meta-analysis had
      revealed an increased risk of death in patients that are treated with PCBA or
      paclitaxel-coated stent. This had led to warning from the United States Food and Drug
      Administration (FDA) and the issue of guidelines from the interventional societies

      Sirolimus coated balloon (SCB) is the new generation of drug-eluting balloons available in
      the market. Compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high
      margin of safety. It has a high transfer rate to the vessel wall and effectively inhibits
      neointimal hyperplasia in the porcine coronary model. In the coronary artery interventions,
      preliminary clinical studies using SCB have also shown excellent procedural and 6-month
      patency.

      The effectiveness of SCB in patients with dialysis access dysfunction has been shown in a
      small pilot study in the salvage of thrombosed AVG and investigators postulate that SCB will
      be a viable option in patients who requires treatment with drug-coated balloon.

      The investigators aim to conduct a multicenter double-blinded randomized controlled trial to
      compare the 6 month unassisted patency rate of SCB angioplasty versus plain balloon
      angioplasty in the management of stenosis in arteriovenous fistula.

      RECRUITMENT:

      Patients with matured AVF (in use for more than 1 month) that are dysfunctional and are
      already scheduled to undergo balloon angioplasty will be considered for the trial. Patients
      will be consented if they fulfill the preliminary eligibility criteria and are agreeable to
      participate in the study. Once all the eligibility criteria are fulfilled, including
      angiographic criteria assessed on the day of the procedure, the patient is entered into the
      trial and randomised. Patients who are unsuitable for the trial will be treated in the
      conventional way with PB and considered as screen failure.

      STUDY PROCEDURE:

      The AVF will be assessed with ultrasound for possible access sites. All patients will undergo
      a fistulogram which is obtained by injection of contrast. The access site will be left to the
      discretion of the procedurist. The fistulogram should include the entire dialysis circuit
      from the arteriovenous anastomosis to the central veins. The suggested approach would include
      a fistulogram via an 18 Gauge cannula inserted into the arterialised vein. When there is no
      spontaneous reflux of contrast into the artery, reflux opacification of the arteriovenous
      (AV) anastomosis is achieved by injecting contrast during inflation of a blood pressure cuff
      or a tourniquet around the arm. Alternatively, a trans-radial or arterial approach may be
      used to obtain the fistulogram

      Based on fistulogram findings, the access site will be placed up to the discretion of the
      procedurist. If an 18G cannula is used, it may be exchanged for a vascular sheath that is
      sized appropriately based on the planned balloon sizes). Alternatively, the 18G cannula may
      be removed and a new access site for intervention may be chosen. A new puncture will be
      performed with the insertion of a vascular sheath (sized appropriately according to planned
      balloon sizes). Two access sites (both antegrade and retrograde) may be needed in certain
      cases. A trans-radial or arterial approach may also be considered if necessary

      In the event that opacification of the anastomosis was not earlier achieved even with
      inflation of a blood pressure cuff around the arm, it will be performed via contrast
      injection through a catheter in the feeding artery.

      When there is more than 1 stenosis, all the lesions will be labelled and treated with
      conventional balloon angioplasty (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 or lesions will be dilated with standard angioplasty that is sized similar
      to the adjacent reference vessel. Inflation time will be at least 1 minute per inflation. The
      balloon will be inflated to an appropriate inflation pressure as per institution standardised
      practice to achieve <30% residual stenosis and satisfactory thrill. If there is significant
      residual stenosis after angioplasty (defined as > 30% stenosis), repeat angioplasty with the
      same standard angioplasty balloon or a larger standard angioplasty balloon may be used at
      operator's discretion. High-pressure angioplasty balloon or cutting balloon may also be used,
      if necessary, in the event of resistant stenosis. In stenotic segment adjacent to aneurysmal
      segment, where the percentage of stenosis is difficult to determine, the treated segment
      should reach at least reach 6mm.

      Randomisation occurs when all the lesions are treated adequately, defined as less than 30%
      residual stenosis after standard treatment.

      Patients will be randomised to receive either the sirolimus coated balloon or plain balloon.
      Repeated angioplasty of the stenotic segments that were successfully treated (defined as less
      than 30% residual stenosis) will be performed using sirolimus coated balloon (for patient
      randomised into the sirolimus balloon arm) or plain/placebo balloon (for patients randomised
      into the placebo arm)

      POST-PROCEDURE ULTRASOUND SCAN:

      All participants will receive an ultrasound scan of their AVF after their procedure before
      discharge. The diameter of the vessel at the treated sites will be measured and documented.
      Brachial artery flow and flow within the outflow vein will also be measured and documented

      * Patency definitions are defined based on SIR reporting standards (Gray et al., 2003):

      Post-intervention target lesion patency:

      Interval after intervention until the next re-intervention at or adjacent to the original
      treatment site or until the access is abandoned. Percutaneous or surgical treatments of a new
      arterial or venous outflow stenosis/occlusion (including access thrombosis) that do not
      involve or exclude the original lesion from the access circuit are compatible with lesion
      patency. The creation of new access that incorporates the target lesion into the new access
      circuit is also compatible with target lesion patency.

      Post-intervention access circuit primary patency:

      Interval following intervention until the next access thrombosis or repeated intervention. It
      ends with the treatment of a lesion anywhere within the access circuit, from the arterial
      inflow to the superior vena cava-right atrial junction.

      Post-intervention access circuit assisted primary patency:

      Interval after intervention until access thrombosis or surgical intervention that excludes
      the treated lesion from the access circuit. Percutaneous treatments of either
      restenosis/occlusion of the previously treated lesion or a new arterial or venous outflow
      stenosis/occlusion (excluding access thrombosis) are compatible with assisted primary
      patency.

      Post-intervention access circuit secondary patency:

      Interval after intervention until the access is surgically declotted, revised or abandoned.
      Thrombolysis and percutaneous thrombectomy are compatible with secondary patency.

      ^Complications will be categorised according to SIR definitions of minor or major
      complications (Aruny et al., 2003):

      A major complication is defined as one that:

        1. require therapy, minor hospitalisation (< 48 hours),

        2. require major therapy, unplanned increase in the level of care, prolonged
           hospitalisation (>48 hours),

        3. leads to permanent adverse sequelae, or

        4. death

      A minor complication is one that:

        1. requires no therapy with no consequence,

        2. requires nominal therapy with no consequence; includes overnight admission for
           observation only.

      POST-PROCEDURE FOLLOW-UP ULTRASOUND SCAN OF AVF:

      Patients will be followed-up at:

      3 months (± 1 weeks): assessment of primary outcome 6 months (± 4 weeks): assess the target
      lesion and access circuit. 12 months (± 4 weeks): assess AVF patency and study closure
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomly allocated in a 1:1 ratio into either the treatment (SCB) arm or control (PB) arm. As above-elbow AVFs generally have larger vessel size and better outcomes compared to below-elbow AVFs, randomisation will be stratified by location of AVF (above vs below elbow) to ensure a more even distribution of AVF by location between both groups.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Dialysis centre staff and procedurist performing the intervention will also be masked
measure: Primary patency of the AVF at 6 months
time frame: 6 months
description: This is measured by the percentage of patients whose AVF remain patent at 6 months after the procedure
measure: Time taken to the next intervention
time frame: Through study completion, an average of 1 year
description: The number of months from procedure to the next interventions. This will be track until study completion.
measure: Treated lesion percent stenosis at 6 and 12 month ultrasound
time frame: 6 and 12 months
description: Defined as percent stenosis relative to adjacent reference vessel, [1 - (minimum lesion diameter / reference vessel diameter)] x 100)
measure: Treated lesion re-stenosis rate at 6 months
time frame: 6 months
description: Defined as incidence of stenosis > 50% diameter of adjacent reference vessel segment
measure: Number of repeat interventions to treated lesion at 6 and 12 months
time frame: 6 and 12 months
description: How many repeat interventions to treated lesion at 6 and 12 months
measure: Number of repeat interventions to maintain access circuit (including interventions to treated lesion) at 6 and 12 months
time frame: 6 and 12 months
description: How many repeat interventions to maintain access circuit (including interventions to treated lesion) at 6 and 12 months
measure: Treated lesion revascularisation free interval
time frame: anytime within 12 months study participation
description: Defined as the interval from intervention to repeat clinically driven target lesion intervention
measure: De nova stenosis detected on ultrasound scan at 3, 6 and 12 months
time frame: 3, 6 and 12 months
description: Presence of De nova stenosis detected on ultrasound scan at 3, 6 and 12 months
measure: Post intervention treated lesion patency at 3, 6 and 12 months
time frame: 3, 6 and 12 months
description: Percentage of patients whose treated stenosis remains patent at 3, 6, and 12 months after the procedure. This is determined by the use of ultrasound imaging or angiogram or clinical examination.
measure: Post-intervention primary patency at 3, 6 and 12 months
time frame: 3, 6 and 12 months
description: Percentage of patients whose AVF remains patent and does not require any further interventions at 3, 6, and 12 months after the procedure. This is determined by the use of ultrasound imaging or angiogram or clinical examination.
measure: Post-intervention assisted primary patency at 3, 6 and 12 months
time frame: 3, 6 and 12 months
description: Percentage of patients whose AVF requires additional interventions to remains patent at 3, 6, and 12 months after the procedure. This is determined by clinical history during the study period
measure: Post-intervention secondary patency at 3, 6 and 12 months
time frame: 3, 6 and 12 months
description: Percentage of patients whose AVF has thrombosed and required additional procedure to restore flow at 3, 6, and 12 months after the procedure. This is determined by clinical history during the study period.
measure: Complication rates at 1, 3, 6 and 12 months
time frame: 1, 3 6 and 12 months
description: Complication rates at 1, 3, 6 and 12 months
arm group label: Sirolimus coated balloon
arm group type: Experimental
description: The trial product is MagicTouch sirolimus drug coated balloon (Concept Medical). Sirolimus will be transferred from the balloon to the vessel wall by inflating the sirolimus coated balloons at 2 minutes at rated burst pressure (typically 12 to 14ATM). All the lesions within the dialysis circuit with sirolimus coated balloon.
arm group label: Plain balloon
arm group type: Placebo Comparator
description: The plain balloon or placebo will not be coated. The plain balloon will be inflated at 2 minutes at rated burst pressure (typically 12 to 14 ATM). Plain balloon will be applied to all the narrowed segment of the dialysis circuit
intervention type: Device
intervention name: Sirolimus coated balloon
description: Sirolimus has a high transfer rate to the vessel wall and effectively inhibit neointimal hyperplasia in the porcine coronary model. In coronary artery interventions, preliminary clinical studies using sirolimus coated balloon have shown excellent procedural and 6 month patency. The effectiveness of sirolimus coated balloon in patients with dialysis access dysfunction has been shown in a small pilot study in the salvage of thrombosed arteriovenous graft.
When compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high margin of safety.
arm group label: Sirolimus coated balloon
intervention type: Device
intervention name: Plain balloon
description: Plain balloon angioplasty is the current standard therapy to treat stenosis in dialysis access. However, the mid and long term patency of plain balloon angioplasty in patients with end stage renal disease is poor. The average primary patency is around 40 to 50 percent at 1 year and multiple repeated angioplasty is required to maintain the patency of the vascular access.
arm group label: Plain balloon
criteria: 
gender: All
minimum age: 21 Years
maximum age: 85 Years
healthy volunteers: No
last name: Chieh Suai Tan, MD
role: Principal Investigator
affiliation: Singapore General Hospital
last name: Chieh Suai Tan, MD
phone: +6581231127
email: tan.chieh.suai@singhealth.com.sg
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country: Singapore
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responsible party type: Sponsor
mesh term: Kidney Failure, Chronic
mesh term: Sirolimus
sharing ipd: Undecided