Clinical trial NCT04381754: Use of Implanting the Biotronik Passeo-18 Lux Drug Coated Balloon to Treat Failing Haemodialysis Arteriovenous Fistulas and Grafts.
Official title: Use of Implanting the Biotronik Passeo-18 Lux Drug Coated Balloon to Treat Failing Hemodialysis Arteriovenous Fistulas and Grafts
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Arterio-venous Fistula
Dialysis Access Malfunction
Hemodialysis Access Failure
Arteriovenous Graft Stenosis
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
First posted: 2020-05-11
Enrollment: 100
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have a native upper limb AVF or AVG, that is currently in use for haemodialysis, which has a significant inflow or outflow stenosis. Significant stenosis defined as diameter greater than 50% compared to adjacent normal segment and/or other evidence of AVF malfunction. Malfunction defined as the AVF performing inadequate dialysis and clinical signs of a failing dialysis access. Inadequate fistula volume flow - Qa as measured by ultrasound \< 500mL/min as probably inadequate. Dialysis numbers: - Qb - a significant stenosis is suggested when the pump speed is \< 200ml/min, venous pressure is \> 140 mmHg and/or arterial pressure \> - 100mmHg. Maximum of 2 discrete stenoses (separated by \> 3cm) are allowed to be included.

Brief summary: 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 is associate 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 showed that DCB appears to be a better and safe alternative to conventional balloon angioplasty (CBA) in treating patients with HD stenosis based on 6- and 12-months primary patency and increased intervention free period.

The Passeo-18 Lux (Biotronik Asia Pacific Pte Ltd (Singapore)) drug-coated balloon (DCB) is packaged with a low dose of paclitaxel. Recent studies have shown that low dose coating of paclitaxel with this DCB is useful for preventing restenosis, decrease lumen loss and target lesion revascularization in the peripheral vasculature6 but has not been tested in the dialysis access circuit.


Eligibility criteria: 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 hemodialysis sessions utilizing 2 needles
* Target lesion location had to be located between the anastomosis to the axillary-subclavian vein junction, as defined by insertion of the cephalic vein.
* On initial fistulogram, target lesion stenosis had to be \>50% on angiographic assessment and in keeping with the clinical indicator for intervention
* Stenosis had to be \< 10cm in length to allow for potential treatment with one PCB (length 12 cm) only
* Stenosis had to be initially treated successfully with a high-pressure plain balloon prior to PCB treatment as defined by:

  1. No clinically significant dissection
  2. No extravasation requiring treatment/stenting
  3. Residual stenosis ≤20% by angiographic measurement
  4. Ability to completely efface the lesion waist using the pre-dilation balloon
* No more than one additional ("nontarget") lesions in the access circuit that had to be also successfully treated (≤30% residual stenosis) before drug elution. Separate lesion was defined by at least 3 cm in distance from the target lesion.
* Reference vessel diameter 4mm - 8mm

Exclusion Criteria:

* Women who were pregnant, lactating, or planning on becoming pregnant during the study
* Subject had 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 thrombosed access or an access with thrombosis treated ≤30 days prior to the index procedure
* Surgical revision of the access site performed, planned or expected ≤ 3 months before or after the index procedure
* Patients who were taking immunosuppressive therapy or are routinely taking ≥ 15 mg of prednisone per day;
* Currently participating in an 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 paclitaxel

Primary outcomes:
measure: 6-month Target Lesion Primary Patency
timeFrame: 6-month post-procedure
Secondary outcomes:
measure: Primary Patency
timeFrame: 12 months post-op
measure: Primary assisted patency
timeFrame: 12 months post-op
measure: Secondary Patency
timeFrame: 12 months post-op
measure: Number of reinterventions
timeFrame: 12 months post-op
measure: Adverse Events
timeFrame: 12 months post-op
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Sinapore General Hospital
name: Tang Tjun Yip
role: PRINCIPAL_INVESTIGATOR
affiliation: Singapore General Hospital
name: Yap Hao Yun
role: PRINCIPAL_INVESTIGATOR
References:
citation: Troisi N, Frosini P, Somma C, Romano E, Guidotti A, Dattolo PC, Ferro G, Chisci E, Michelagnoli S. Drug-coated balloons reduce the risk of recurrent restenosis in arteriovenous fistulas and prosthetic grafts for hemodialysis. Int Angiol. 2018 Feb;37(1):59-63. doi: 10.23736/S0392-9590.17.03886-X. Epub 2017 Nov 10.
citation: Liao MT, Chen MK, Hsieh MY, Yeh NL, Chien KL, Lin CC, Wu CC, Chie WC. Drug-coated balloon versus conventional balloon angioplasty of hemodialysis arteriovenous fistula or graft: A systematic review and meta-analysis of randomized controlled trials. PLoS One. 2020 Apr 14;15(4):e0231463. doi: 10.1371/journal.pone.0231463. eCollection 2020.
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: Khawaja AZ, Cassidy DB, Al Shakarchi J, McGrogan DG, Inston NG, Jones RG. Systematic review of drug eluting balloon angioplasty for arteriovenous haemodialysis access stenosis. J Vasc Access. 2016 Mar-Apr;17(2):103-10. doi: 10.5301/jva.5000508. Epub 2016 Feb 5.
citation: Yan Wee IJ, Yap HY, Hsien Ts'ung LT, Lee Qingwei S, Tan CS, Tang TY, Chong TT. A systematic review and meta-analysis of drug-coated balloon versus conventional balloon angioplasty for dialysis access stenosis. J Vasc Surg. 2019 Sep;70(3):970-979.e3. doi: 10.1016/j.jvs.2019.01.082.
citation: Brodmann M, Zeller T, Christensen J, Binkert C, Spak L, Schroder H, Righini P, Nano G, Tepe G. Real-world experience with a Paclitaxel-Coated Balloon for the treatment of atherosclerotic infrainguinal arteries: 12-month interim results of the BIOLUX P-III registry first year of enrolment. J Vasc Bras. 2017 Oct-Dec;16(4):276-284. doi: 10.1590/1677-5449.007317.