Delivery of Inhibitors of Lysyl Oxidase (LysoLox) on Serial Angioplasty and Time to Restenosis

Southeast Renal Research Institute

Status and phase: Unknown; Phase 2

Conditions: Arteriovenous Fistula Occlusion

Treatments: Drug: Ascorbic Acid; Drug: Placebo; Drug: Cuprimine Oral Product

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03106948

Lysyl Oxidase (LysoLox)

Details and patient eligibility

About

The narrowing of Dialysis Fistulae or Grafts is a near universal problem in patients with end-stage renal disease (ESRD) and requires patients to undergo repeated angioplasty or mechanical opening of the fistula.

Full description

The failure of dialysis accesses remains a leading cause of morbidity and medical costs among ESRD subjects. The underlying etiology for dialysis access failure is uniformly due to progressive narrowing of the vessel lumen leading to stasis and thrombosis of the access. The luminal narrowing of arteriovenous fistulae (AVFs) is due to progressive hyperplasia of vessel intima and subsequent infiltration of smooth muscle cells into the vessel media. Areas of stenosis within AVFs are characterized by dense neointimal hyperplasia, infiltration of vascular smooth muscle cells and expansion of extracellular matrix material. Additionally, varying types of vascular injury increase the rate of collagen and elastin deposition within the medial and serosal areas of the vessel.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 and < 90 years old

• Receiving stable out-subject hemodialysis for a minimum of 3 months

• Have a lower arm or upper arm AVF that has been cleared for use by the vascular surgeon or interventional nephrologist

• Have agreed to participate voluntarily and signed and dated an IRB approved, subject informed consent form

• Dysfunctional Dialysis Fistula: Any subject with

  • Two or more venous pressure readings exceeding 250 mmHg for a minimum of 5 minutes at a blood flow of 500mls/min within a single dialysis run AND a documented reduction in KT/V by > 0.2; OR
  • Patients with venous pressures > 250 mm Hg on two or more days within a 30 day period OR
  • Patients who on physical exam are found to have palpable obstructions, post-stenotic dilation of the access or evidence of prolonged post-dialysis bleeding.

• Any patient with one of the above conditions will be to have a dysfunctional AVF. This definition will be applied to the screening of study subjects as well as the determination of recurrent fistula dysfunction at 12 months.

Exclusion criteria

• Scheduled for surgical revision of the fistula;

• Have been in another investigational (non-approved) drug or device study within the previous 30 days;

  **have a known allergy to any component of the investigational product (drug or device)

• Subjects with a "Hero Graft" will be excluded from the study

• Subjects having received a stent for correction of a prior stenosis will be excluded from the trial

• Subjects with more than > 3 hemodynamically significant stenosis at one time (with the exception of a central venous stenosis)

• Subjects who are pregnant will be excluded from the trial (pregnancy test will be performed on subjects of child bearing potential). A urine pregnancy test will be utilized.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups, including a placebo group

Low frequency angioplasty

Placebo Comparator group

Description:

Subjects who have had 0-1 angioplasty during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty but will not have insertion of the ACT drug delivery catheter

Treatment:

Drug: Placebo

Moderate frequency angioplasty

Active Comparator group

Description:

Subjects who have had 2-3 angioplasties during the 12 months prior to randomization. Subjects will have endoluminal biopsy prior to angioplasty followed by insertion of the ACT drug delivery catheter where ascorbic acid (10.0 µM) will be injected following conventional balloon angioplasty

Treatment:

Drug: Ascorbic Acid

High frequency angioplasty

Active Comparator group

Description:

High frequency angioplasty defined by 4 or more angioplasties 12 months prior to randomization. Subjects will receive ascorbic acid (10.0 µM) in combination with D-penicillamine (25 µM) will be injected following conventional balloon angioplasty

Treatment:

Drug: Cuprimine Oral Product