Paclitaxel for the Treatment of Upper-Extremity Arteriovenous Access Fistula Stenosis (PaciFIST-1)

The Use of Intravascular Paclitaxel for the Treatment of Upper-Extremity Arteriovenous Access Fistula Stenosis: A Randomized Study

The objective of this study is to evaluate the safety and effectiveness of the use of intravascular paclitaxel, in addition to standard therapy, for the treatment of arteriovenous dialysis access fistula stenosis.

A fistulogram will be performed in standard fashion. The diagnostic component will include evaluation of the inflow artery, arterial anastomosis and full length of the fistula vein or graft, plus venous return up to the heart. The location, vessel size, lesion diameter and percent stenosis for each lesion will be recorded. Enrollment and randomization will occur at this point.

All patients will then receive standard therapy for their stenosis. This will include intravenous heparin administered in a standard dose of 70 units/kg. Lesions that respond poorly to angioplasty (>30% residual stenosis after angioplasty treatment with 2 inflations) will be stented. Stent selection will be based on clinical setting. Initial stent treatment will utilize an uncovered nitinol stent. Treatment of in-stent restenosis will include initial balloon angioplasty, and use of a covered stent (Viabahn, GORE, or Fluency, Bard). Documentation of location and type of treatment for each lesion treated will be recorded.

Once standard treatment is completed, the operating surgeon will be informed of the patient randomization: treatment (paclitaxel) or control. For subjects assigned to treatment, Paclitaxel solution treatment of each lesion encountered from proximal to distal will be attempted until the 20 mg Paclitaxel dose limit is met.

A TAPAS infusion catheter will be used for all paclitaxel dose administrations. The TAPAS infusion catheter will be positioned to reduce the presence of branches which permit the loss of paclitaxel from the treatment zone. After the full outflow vein segment is treated, the fistulogram is completed in the standard fashion. Prior to removal of the sheath, a final angiographic study of all areas treated is performed to document patency and lesion appearance.

For the control group, instead of paclitaxel administration, a sham treatment period of 10 minutes is allowed to elapse followed by the performance of the final completion angiogram. Any additional lesions identified with this study are then treated appropriately following standard technique.

All patients will follow the same follow up evaluation schedule.

Study Overview

• Status: Terminated
• Conditions: Fistula Stenosis
• Intervention / Treatment: Procedure: Standard Therapy; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years or older
2. Patient or guardian able to provide a signed witnessed informed consent
3. Stenosis greater than or equal to 50% treated satisfactorily (less than 20% residual stenosis) with balloon angioplasty alone or balloon angioplasty and stent placement
4. Either gender

Exclusion Criteria:

1. Women who are pregnant or who are expected to or might become pregnant
2. Women of child-bearing potential who do not use contraception
3. Life expectancy less than 12 months
4. Known allergy to paclitaxel
5. Known allergy to contrast media not previously demonstrated to be controllable with premedication on a prior study using contrast
6. Known allergy to the pre-medications (dexamethasone, famotidine, diphenhydramine)
7. Pre-fistulogram thrombosis of the fistula or graft
8. Thrombectomy of the fistula or graft within 14 days of the procedure
9. Patient receiving chemotherapy
10. Patients with an immunodeficiency disease or condition
11. Documented hypercoagulable state
12. White Blood Count < 2000/mm3
13. Platelet count less than 100,000/mm3
14. Chronic hepatitis or jaundice (total bilirubin > 2x upper limit of normal)
15. Simultaneous enrollment in another investigational device or drug study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: Standard Therapy Alone; Standard treatment of all stenotic lesions will be carried out in the usual fashion. Intravenous heparin will be administered in a standard dose of 70 units/kg. Lesions that respond poorly to angioplasty (>30% residual stenosis after angioplasty treatment with 2 inflations) will be stented. Stent selection will be based on clinical setting. Initial stent treatment will utilize an uncovered nitinol stent. Treatment of in-stent restenosis will include initial balloon angioplasty, and use of a covered stent (Viabahn, GORE, or Fluency, Bard). For this "control" group, no paclitaxel is administered. The sham treatment is a period of 10 minutes that is allowed to elapse followed by the performance of a final completion angiogram to be labeled as "PaciFIST Study Completion Angiogram." Any additional lesions identified with this study are then treated appropriately following standard technique.	Procedure: Standard Therapy; Standard treatment of all stenotic lesions will be carried out in the usual fashion. Intravenous heparin will be administered in a standard dose of 70 units/kg. Lesions that respond poorly to angioplasty (>30% residual stenosis after angioplasty treatment with 2 inflations) will be stented. Stent selection will be based on clinical setting. Initial stent treatment will utilize an uncovered nitinol stent. Treatment of in-stent restenosis will include initial balloon angioplasty, and use of a covered stent (Viabahn, GORE, or Fluency, Bard).; Other Names: heparin; stents; angioplasty
ACTIVE_COMPARATOR: Standard Therapy Plus Paclitaxel; Standard treatment of all stenotic lesions will be carried out in the usual fashion. Intravenous heparin will be administered in a standard dose of 70 units/kg. Lesions that respond poorly to angioplasty (>30% residual stenosis after angioplasty treatment with 2 inflations) will be stented. Stent selection will be based on clinical setting. Initial stent treatment will utilize an uncovered nitinol stent. Treatment of in-stent restenosis will include initial balloon angioplasty, and use of a covered stent (Viabahn, GORE, or Fluency, Bard). For this "treatment" group, Paclitaxel solution treatment of each lesion encountered from proximal to distal will be attempted until the 20 mg Paclitaxel dose limit is met.	Procedure: Standard Therapy; Standard treatment of all stenotic lesions will be carried out in the usual fashion. Intravenous heparin will be administered in a standard dose of 70 units/kg. Lesions that respond poorly to angioplasty (>30% residual stenosis after angioplasty treatment with 2 inflations) will be stented. Stent selection will be based on clinical setting. Initial stent treatment will utilize an uncovered nitinol stent. Treatment of in-stent restenosis will include initial balloon angioplasty, and use of a covered stent (Viabahn, GORE, or Fluency, Bard).; Other Names: heparin; stents; angioplasty; Drug: Paclitaxel; Paclitaxel solution treatment of each lesion encountered will be attempted until the 20 mg Paclitaxel dose limit is met. The volume administered will depend on the diameter and length of the venous outflow segment.; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Lesion Revascularization.	Target lesion revascularization (TLR) is defined as the need for subsequent clinically driven repeat angioplasty, stent placement or other intervention to correct the recurrence of a stenosis at the site treated within 6 months of the initial treatment.	6 months
Target Segment Revascularization.	Target segment revascularization (TSR) is defined as the need for secondary clinically driven repeat angioplasty, stent placement or other intervention to correct the recurrence of a stenosis in the outflow segment of cephalic vein treated with paclitaxel.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall safety based on SAEs	The overall serious adverse event (SAE) rate will be determined as well as the rate for each individual type of adverse occurrence or event.	6 months
Binary Restenosis	The development of recurrent stenosis of the site treated with angioplasty or angioplasty and stent followed by the paclitaxel controlled infusion. The presence of a binary stenosis is defined as a 50% decrease of the vessel diameter measured on the fistulogram.	6 months
Primary Patency: Fistula	The interval from treatment until access thrombosis or repeat intervention treatment to maintain fistula function, or the abandonment of the fistula.	6 months

Collaborators and Investigators

• Sponsor: Englewood Hospital and Medical Center
• Collaborators: Spectranetics Corporation

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: May 29, 2013
• First Submitted That Met QC Criteria: May 31, 2013
• First Posted (ESTIMATE): June 5, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Fistula; Constriction, Pathologic; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Anticoagulants; Paclitaxel; Heparin
• Other Study ID Numbers: E-12-468