Sirolimus Coated Angioplasty Versus Plain Balloon Angioplasty

NCT04409912 | Unknown

• 1 other identifier: 2019/2896
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

End Stage Renal Failure on Dialysis; Arteriovenous Graft Occlusion

Outcome Measures

Primary Outcomes (1)

• Primary patency of the AVF at 6 months

  This is measured by the percentage of patients whose AVF remain patent at 6 months after the procedure

  6 months

Secondary Outcomes (12)

• Time taken to the next intervention

  Through study completion, an average of 1 year

• Treated lesion percent stenosis at 6 and 12 month ultrasound

  6 and 12 months

• Treated lesion re-stenosis rate at 6 months

  6 months

• Number of repeat interventions to treated lesion at 6 and 12 months

  6 and 12 months

• Number of repeat interventions to maintain access circuit (including interventions to treated lesion) at 6 and 12 months

  6 and 12 months

Study Arms (2)

Sirolimus coated balloon

EXPERIMENTAL

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.

Device: Sirolimus coated balloon

Plain balloon

PLACEBO COMPARATOR

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

Device: Plain balloon

Interventions

Sirolimus coated balloon DEVICE

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.

Sirolimus coated balloon

Plain balloon DEVICE

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.

Plain balloon

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 to 85 years
• Patient who requires balloon angioplasty for dysfunction arteriovenous fistula
• Matured AVF, defined as being in use for at least 1 month prior to angioplasty
• \. Successful 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.)

You may not qualify if:

• Patient unable to provide informed consent
• Thrombosed or partially thrombosed AVF
• Presence of symptomatic or angiographically significant central vein stenosis who require treatment, with more than 30% residual stenosis post angioplasty
• Patients who had underwent stent placement within the AVF circuit
• Patient who are currently enrolled in other drug eluting balloon trials
• Sepsis or active infection
• Recent intracranial bleed or gastrointestinal bleed within the past 12 months
• Allergy to iodinated contrast media, anti-platelet drugs, heparin or sirolimus
• Pregnancy

Sponsors & Collaborators

• Singapore General Hospital: lead
• National University Hospital, Singapore: collaborator
• Sengkang General Hospital: collaborator

Study Sites (3)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Singapore General Hospital

Singapore, 169608, Singapore

RECRUITING

Sengkang General Hospital

Singapore, 544886, Singapore

RECRUITING

Related Publications (20)

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  PMID: 16565259 BACKGROUND

• 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.

  PMID: 19695501 BACKGROUND

• Pantelias K, Grapsa E. Vascular access today. World J Nephrol. 2012 Jun 6;1(3):69-78. doi: 10.5527/wjn.v1.i3.69.

  PMID: 24175244 BACKGROUND

• 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.

  PMID: 26111994 BACKGROUND

• Office NRoD: Trends in Chronic Kidney Failure Stage 5 in Singapore 2012 / 2013. In.

  BACKGROUND

• 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.

  PMID: 15286321 BACKGROUND

• 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.

  PMID: 11230644 BACKGROUND

• 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.

  PMID: 21955605 BACKGROUND

• 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.

  PMID: 20147715 BACKGROUND

• 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.

  PMID: 18829240 BACKGROUND

• 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.

  PMID: 20507955 BACKGROUND

• 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.

  PMID: 17699495 BACKGROUND

• 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.

  PMID: 22545894 BACKGROUND

• 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.

  PMID: 30857987 BACKGROUND

• 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.

  PMID: 30561254 BACKGROUND

• Updated CIRSE Position Statement on the use of paclitaxel-coated balloons and stents in peripheral arterial disease.https://www.cirse.org/research/current-updates/

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 27069105 BACKGROUND

• 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.

  PMID: 28964764 BACKGROUND

• Pang SC, Tan RY, Choke E, Ho J, Tay KH, Gogna A, Irani FG, Zhuang KD, Toh L, Chan S, Krishnan P, Lee KA, Leong S, Lo R, Patel A, Tan BS, Too CW, Chua J, Tng RKA, Tang TY, Chng SP, Chong TT, Tay HT, Yap HY, Wong J, Dharmaraj RB, Ng JJ, Gopinathan A, Loh EK, Ong SJ, Yoong G, Tay JS, Chong KY, Tan CS. SIroliMus coated angioPlasty versus plain balloon angioplasty in the tREatment of dialySis acceSs dysfunctION (IMPRESSION): study protocol for a randomized controlled trial. Trials. 2021 Dec 20;22(1):945. doi: 10.1186/s13063-021-05920-3.

  PMID: 34930401 DERIVED

Study Officials

• Chieh Suai Tan, MD

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chieh Suai Tan, MD

CONTACT

+6581231127; tan.chieh.suai@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Dialysis centre staff and procedurist performing the intervention will also be masked
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: June 1, 2020
• Study Start: January 11, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2024
• Last Updated: August 6, 2021

Record last verified: 2021-08

Locations

SG (3)