RCT of Paclitaxel DEB Compared to Standard PTA in Dialysis Fistula (APERTO)

A Randomized Trial of Aperto Paclitaxel Eluting Dilatation Catheter Compared to POBA in Dialysis Fistula

A multicenter randomized clinical trial of paclitaxel drug-eluting balloon (DEB) versus standard percutaneous transluminal angioplasty (PTA) to reduce restenosis in 150 patients with haemodialysis access stenoses.

Study Overview

• Status: Completed
• Conditions: Vascular Access Complication; Complication of Hemodialysis
• Intervention / Treatment: Device: DEB, drug eluting balloon; Device: standard PTA

Detailed Description

Prospective multicenter randomized (1:1) Investigator Sponsored Trial, in which 150 consecutive patients candidates for percutaneous intervention of haemodialysis access will be randomly assigned to one of two study arms:

1. Treatment Arm: paclitaxel drug-eluting balloon (DEB) dilatation using the APERTO-balloon
2. Control Arm: standard percutaneous transluminal angioplasty (PTA).

The aim is to evaluate the safety and efficacy of paclitaxel drug-eluting balloon (DEB) for the reduction of restenosis in haemodialysis shunts compared to standard percutaneous transluminal angioplasty (PTA).

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • ZNA Stuivenberg
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • UMC Groningen
  • Friesland
    • Leeuwarden, Friesland, Netherlands, 8934 AD
      • MC Leeuwarden
  • Limburg
    • Heerlen, Limburg, Netherlands, 6419 PC
      • Atrium Medisch Centrum. Department of radiology
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Catharina Ziekenhuis
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1061 AE
      • St Lucas Andreas Hospital
  • ZH
    • Gouda, ZH, Netherlands, 2803 HH
      • Groene Hart Ziekenhuis
  • Zuid Holland
    • Den Haag, Zuid Holland, Netherlands, 2512 VA
      • MC Haaglanden
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015CE
      • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All criteria 1-10 must apply for inclusion.

1. Age > 18 years and < 90 years
2. Patient or legally authorized representative providing written informed consent
3. Patient willing and likely to comply with the follow up schedule

4. Patients with previously well functioning hemodialysis access on the arm presenting with any of the following clinical abnormalities as defined in the NKF-DOQI-protocol criteria (National Kidney Foundation 2000):

   • Abnormal physical examination findings (change in bruits, thrill, pulse, etc
   • Abnormal urea recirculation measurements
   • Elevated venous pressure during dialysis
   • Decreased access flow
   • Previous thrombosis in the access line
   • Development of collateral veins
   • Limb swelling
   • Low arterial pressure during dialysis
   • Unexplained decreases in dialysis dose
5. Target Lesion is hemodynamically relevant and consists of MLD ≤ 3 mm. For enrolment this criterium is judged by the local investigator. For final analysis this criterium is based on the result of central reading of the angiogram.
6. Target Lesion(s) is a de-novo or (non-stent) restenosis
7. Target lesion(s) in dialysis fistulas is located at the anastomosis or in the outflow venous trajectory up to the level (but excluding) the subclavian vein
8. Target lesion(s) in dialysis grafts is located at the arterial or venous anastomosis, inside the graft, or in the outflow venous trajectory up to the level (but excluding) the subclavian vein
9. Multiple Target Lesions are allowed per patient which can be treated by a number of APERTO DEB with aggregate max length of 160 mm
10. NON Target Lesions (i.e. in the subclavian vein) must be successfully treated with standard PTA prior to the Target Lesion.

Exclusion Criteria:

None of criteria 1-12 must apply for inclusion.

1. Patients unable to give informed consent
2. Patients enrolled in another study with any investigational drug or device
3. Patients previously enrolled in the APERTO trial.
4. Female patients of child bearing potential without a negative pregnancy test at the time of intervention
5. Major surgical procedures within 30 days prior to this study or planned within 30 days of entry into this study
6. Patients previously treated with a DEB in the hemodialysis access.
7. Patients with a trombosed hemodialysis access.
8. Immature hemodialysis access (unusable due to insufficient shunt flow volume)
9. Lesion treated within 30 days prior to screening
10. Failure to successfully treat non-target lesions prior the Target Lesion
11. In stent restenosis
12. Patients with any known allergy, hypersensitivity or intolerance to ASA, clopidogrel or ticlopidine, paclitaxel, or contrast medium.
13. Graft infection
14. Life expectancy < 1 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEB - drug eluting balloon (APERTO); Percutaneous balloon angioplasty performed with the investigational device, the paclitaxel eluting APERTO balloon	Device: DEB, drug eluting balloon; Percutaneous angioplasty performed with a DEB - drug eluting balloon; Other Names: Paclitaxel eluting balloon
Active Comparator: standard PTA; Percutaneous balloon angioplasty performed with the clinical standard, that is, a non-drug-eluting balloon (POBA, plain old balloon angioplasty).	Device: standard PTA; Percutaneous angioplasty performed with a standard balloon; Other Names: POBA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adequate functioning of the hemodialysis access	Period of adequate functioning of the hemodialysis access after treatment, defined according to the NKF-DOQI protocol criteria	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
device success	ability of the DEB to be delivered, inflated at pressure ≤ RBP, and retrieved from the Target Lesion without burst	index procedure (day 0)
Technical Success	achievement of a lumen diameter of at least 70% of the nominal diameter of either the DEB or the post dilatation PTA balloon (whichever is bigger) by visual estimate and without bail-out stenting	index procedure (day 0)
Clinical Success	improvement in haemodialysis access failure and resumption of normal dialysis for at least one dialysis session after the index procedure	12 months
Procedural Success	Technical Success without the occurrence of MAE (MAE defined here as: death, stroke, thrombotic occlusion, allergic reaction, pulmonary events (including pulmonary edema)	Index procedure (day 0)
MAE - major adverse events	MAE defined as: death or stroke	12 months
thrombotic occlusion of target lesion	thrombotic occlusion of target lesion	12 months
thrombotic occlusion of target hemodialysis access	thrombotic occlusion of target hemodialysis access	12 months
Clinically driven Target Lesion Revascularization (TLR)	Clinically driven Target Lesion Revascularization (TLR)	12 months
Clinically driven Target Shunt Revascularization (TSR)	Clinically driven Target Shunt Revascularization (TSR)	12 months

Collaborators and Investigators

• Sponsor: Groene Hart Ziekenhuis
• Collaborators: Archer Research
• Investigators: Principal Investigator: Peter MT Pattynama, MD, PhD, Groene Hart Ziekenhuis

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): July 3, 2019
• Study Completion (Actual): July 3, 2019

Study Registration Dates

• First Submitted: June 7, 2015
• First Submitted That Met QC Criteria: September 22, 2015
• First Posted (Estimate): September 23, 2015

Study Record Updates

• Last Update Posted (Actual): May 5, 2020
• Last Update Submitted That Met QC Criteria: May 1, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: drug eluting balloon; percutaneous balloon angioplasty
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Fistula; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: NL44059.058.13