Sirolimus Coated Angioplasty Balloon in the Salvage of Thrombosed Arteriovenous Graft

NCT03666208 | Completed Phase 2 DMC

• 1 other identifier: SCB
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

End stage renal disease is on increasing trend. Haemodialysis is the main dialysis modality among these patients which accounts for the incidence of 81.3% in 2015 based on data from Singapore renal registry. Thus, A functioning dialysis vascular access (either arteriovenous Fistula or graft) is critical to the delivery of life-saving haemodialysis treatment to these patients. The main focus in our study is thrombosed (blocked) AVG as it has higher thrombosis rate and poorer patency rate. Conventionally, to restore the function of the dialysis access, the thrombus (clot) will be lysed with the use of lytic agent; followed by treatment of the underlying stenosis (narrowing) with plain balloon angioplasty (dilatation). However narrowing often recur and multiple repeated angioplasty procedures are needed keep the AVG flowing to prevent clots formation. Recently developed balloons called drug eluting balloons, are coated with medications to prevent the narrowing from recurring after angioplasty. With these drug balloons, the AVG can potentially continue to have good flow for a longer period of time, hence, decreasing the chance of clotting. A newer generation of drug-eluting balloon, called sirolimus coated balloon, are coated with a medicine called sirolimus. It has been successfully used in the treatment of narrowing of vessels in the leg and heart and it were superior than conventional paclitaxel coated balloon angioplasty. We hypothesis that sirolimus coated balloon is superior to conventional plain balloon angioplasty with decreased re-stenosis of target lesion, improved access circuit and target 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)

• The patency rate of AVG at 3 months post sirolimus balloon angioplasty by performing surveillance ultrasound of AVG, assessing the thrill of AVG and assessing any dysfunctional vascular assess- related hospital admission.

  3 months

Secondary Outcomes (3)

• The patency rate of AVG at 6 months post sirolimus balloon angioplasty by performing surveillance ultrasound of AVG, assessing the thrill of AVG and assessing any dysfunctional vascular assess- related hospital admission.

  6 months

• The number of intervention(s) needed to maintain patency of AVG.

  6 months

• The cost effective of using sirolimus coated balloon in the management of thrombosed AVG by reviewing hospital bills related to dysfunctional dialysis access.

  6 months

Study Arms (1)

Thrombosed Arteriovenous Graft

EXPERIMENTAL

Single arm pilot study to investigate effect of sirolimus coated balloon in thrombosed arteriovenous graft

Device: Sirolimus Coated Balloon

Interventions

Sirolimus Coated Balloon DEVICE

Sirolimus has been used in organ transplantation as well as coronary stent due to its antiproliferative properties. It has been proven to has better outcome in animal studies compared to paclitaxel, which is about 22% in the sirolimus group versus 75% re-stenosis rate in paclitaxel group. Sirolimus is coated on the surface of the angioplasty balloon and is transferred to the vessel wall when balloon is inflated and in contact with the vessel wall. The following table compare sirolimus to paclitaxel. In which sirolimus works by cytostatic mechanism with a ten thousand fold of safety margin. And sirolimus's anti-restenosis effect is optimal with the benefit of lower level of competition and lesser tissue absorption and elution.

Also known as: Drug eluting device

Thrombosed Arteriovenous Graft

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 21-85 years
• Thrombosed AVG in the arm
• Successful thrombolysis of the thrombosed AVG, defined as the re-established of flow on Digital Subtraction Angiography (DSA) and restoration of thrill in the AVG on clinical examination

You may not qualify if:

• Patient unable to provide informed consent
• Previous bare metal stent or stent-graft placement within the dialysis access
• Presence of central vein stenosis
• 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 paclitaxel
• Pregnancy
• Life expectancy \< 12 months based on physician's estimate (active malignancy)

Sponsors & Collaborators

• Singapore General Hospital: lead

Study Sites (1)

Singapore General Hospital Renal Department

Singapore, 169608, Singapore

Location

Related Publications (13)

• 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.

  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 RESULT

• Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl (2011). 2015 Jun;5(1):2-7. doi: 10.1038/kisup.2015.2.

  PMID: 26097778 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Andreini D, Trabattoni D. Is the Sirolimus encapsulated balloon a reliable tool for treating the in-stent restenosis?-insights from the SABRE trial. J Thorac Dis. 2018 Feb;10(2):634-637. doi: 10.21037/jtd.2018.01.05. No abstract available.

  PMID: 29607127 RESULT

• 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 RESULT

• Tan RY, Tan CW, Pang SC, Foo MWY, Tang TY, Gogna A, Chong TT, Tan CS. Study protocol of a pilot study on sirolimus-coated balloon angioplasty in salvaging clotted arteriovenous graft. CVIR Endovasc. 2020 Jul 5;3(1):34. doi: 10.1186/s42155-020-00123-4.

  PMID: 32627114 DERIVED

Study Officials

• Chieh Suai Tan, Doctor

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 2, pilot clinical trial to investigate the effect of SCB on thrombosed AVG. Specifically, we are focusing on AVG as they have a higher thrombosis rate than AVF and the patency rate even after successful thrombolysis is much lower than AVF. As neointimal hyperplasia is the predominant cause for stenosis at the graft vein junction, treatment with Sirolimus will intuitively delay the recurrence of neo-intimal hyperplasia and result in better patency of the AVG after successful thrombolysis. Patients with ESRD presenting with a thrombosed AVG between June 2018 and December 2018 will be screened for suitability. Eligible patients of at least 21 years of age will be offered participation. The potential benefits and risks of SCB will be explained and informed consent obtained from participants. A total of 20 patients will be recruited for the trial and they will be followed up for 6 months after the interventions.

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 11, 2018
• Study Start: July 1, 2018
• Primary Completion: September 2, 2019
• Study Completion: September 2, 2019
• Last Updated: September 10, 2019

Record last verified: 2019-09

Locations

SG (1)