Drug Eluting Balloon for Early Fistula Failure Trial (DEBEFF)

October 3, 2016 updated by: Naveed Ul Haq, King Faisal Specialist Hospital & Research Center
Hemodialysis (HD) remains the most prevalent form of renal replacement therapy (RRT) for patients with End Stage Renal Disease (ESRD). Loss and dysfunction of vascular access is a significant contributor to morbidity in ESRD patients on HD. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines suggest that all ESRD patients should initiate dialysis with a functioning permanent vascular access with arteriovenous fistulas (AVF) preferred over arteriovenous grafts (AVG). Central venous catheters (CVC) are the least preferred vascular access for HD due to the complications associated with them. Despite these recommendations, up to 80% patients start dialysis with a CVC. One of the reasons for low AVF rates is early fistula failure (EFF). The most important causes for EFF amenable to intervention is stenosis anywhere in the circuit. Endovascular approach has shown a high rate of technical success in the treatment of stenotic lesions related to HD arteriovenous access. Percutaneous balloon angioplasty (PBA) is considered the treatment of choice for these lesions. Despite good technical and immediate success PBA has poor long term outcomes with recurrence rates of 60-70% at 6 months. One of the reasons could be the damage caused by angioplasty itself leading to intima-media rupture promoting the cascade of events leading to further development of neo intimal hyperplasia (NIH). Recently the use of covered stents at the time of angioplasty has shown better patency rates at 6 months but still not optimal. Lately the development of drug eluting stents and drug eluting balloons (DEB) have shown considerable advantage in clinical trials related to coronary and peripheral arterial disease angioplasty. In a randomized control trial, the researchers are planning to assess the efficacy of DEB angioplasty as compared to standard PBA in AVF's with EFF.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hemodialysis (HD) remains the most prevalent form of RRT for patients with End Stage Renal Disease (ESRD). Just in the United States there are more than 380,000 patients with ESRD on hemodialysis (HD) and the number is expected to increase to 500,000 by the year 2020. Recent data provided by Saudi Centre for Organ Transplantation (www.scot.org.sa) shows that there are just over 13000 patients with End-stage renal disease (ESRD) on hemodialysis in the Kingdom of Saudi Arabia. This number is expected to rise at a rate of 7-8% annually reaching 18000 by year 2018. Establishing a viable vascular access is crucial and is considered the 'life-line' for such patients. Loss and dysfunction of vascular access is a significant contributor to morbidity in ESRD patients on HD. In the United States <50% of all hemodialysis accesses remain patent at 3 years with the economic burden of maintaining vascular access patency calculated to exceed $1 billion with a >6% annual trend. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines suggest that all ESRD patients should initiate dialysis with a functioning permanent vascular access with arteriovenous fistulas (AVF) preferred over arteriovenous grafts (AVG). Central venous catheters (CVC) are the least preferred vascular access for HD due to the complications associated with them. Despite these recommendations and clear benefits of using arteriovenous access for hemodialysis, up to 80% patients start dialysis with a CVC. One of the reasons for low AVF rates is early fistula failure (EFF). EFF is defined as an AVF that never develops adequately for dialysis (failure to mature) or which fails within 3 months of starting dialysis. An adequate AVF for dialysis according to KDOQI guidelines is the one which a) Has a flow of greater than 600ml/min, b) Has a diameter of 0.6cm or greater and c) Is approximately not deeper than 0.6cm from the skin surface. Between 23%-46% of newly constructed AVF have problems with early failure resulting in a dismal one year patency of 60-65%.

In order to devise a strategy to prevent EFF, one needs to understand the physiology of fistula maturation. Creation of an AVF leads to an immediate increase in flow through the vein due to the pressure gradient created. This increase in flow leads to increase wall shear stress which is defined mathematically by the formula 4ηQ/πr3, where η is blood viscosity, Q is blood flow and r is vessel radius. Shear stress thus is directly proportional to blood flow while inversely proportional to vessel diameter. After the creation of the AVF, the flow mediated increase in shear stress is mitigated by vessel dilatation through biological mediators. Consequently the shear stress is brought back to pre-anastomosis levels leading to vessel dilation. It seems that this positive remodeling of the vein leading to AVF maturation is dependent on increase in blood flow rather than the increase in pressure. Any pathology affecting the blood flow through the newly constructed AVF can thus lead to failure to mature.

The two most important causes for EFF amenable to intervention are stenosis anywhere in the circuit (present in around 80% of EFF) and/or presence of accessory veins. While stenosis development is pathological and accessory vein presence is natural, both lead to decreased blood flow through the main AVF circuit, which may be responsible for failure to mature. Addressing these two entities in a timely fashion can lead to salvage of many AVF, which otherwise would have been abandoned.

Development of neo-intimal hyperplasia (NIH) is the main pathology causing stenosis in the AVF circuit. There are many factors thought to be responsible for the development of this NIH. These include turbulent flow with wall shear stress disturbances, uremic endothelial dysfunction, repeated venipunctures, and unique anatomic factors. The pathogenesis includes migration of smooth muscle cells and myofibroblasts from media to intima, neoangiogenesis of microvessels inside neointima, and high levels of inflammatory blood markers.

Since its introduction, endovascular approach has shown a high rate of technical success in the treatment of stenotic lesions related to HD arteriovenous access. Percutaneous balloon angioplasty (PBA) is considered the treatment of choice for these lesions. Despite good technical and immediate success PBA has poor long term outcomes with recurrence rates of 60-70% at 6 months. One of the reasons could be the damage caused by angioplasty itself leading to intima-media rupture promoting the cascade of events leading to further development of NIH. Recently the use of covered stents at the time of angioplasty has shown better patency rates at 6 months but still not optimal. Lately the idea of delivering loco-regional pharmacological agents at the time of angioplasty to prevent NIH from happening has been extensively studied mostly in coronary arteries. This lead to the development of drug eluting stents and drug eluting balloons (DEB). These therapies have shown considerable advantage in clinical trials related to coronary and peripheral arterial disease. Although promising but advantages in coronary and peripheral arteries may not be applicable to arteriovenous access where the lesions are mostly venous with different characteristics. The role of these more costly interventions needs to be addressed in stenosis related to AVF, before wide spread use can be recommended. In a recent randomized non-blinded study involving 40 patients, Kostanos et al showed better 6 month patency rates (70% vs 25%) with DEB angioplasty as compared to standard PBA. The study is non-blinded and involved both AVG and AVF with target lesion spread all over the arteriovenous access circuit. Patane et al recently performed a study on 26 failing radiocephalic AVF's with juxta-anastamosis stenosis, defined as stenosis within 3 cm of arteriovenous anastamosis. In this study DEB angioplasty showed a 6 month primary patency of 96.1% which is much higher than historical conventional balloon angioplasty. The investigators targeted a lesion which resembles more closely arterial lesions where DEB has been shown to be effective, which seems more reasonable but there were no controls in the study. Due to the lack of a control group such high patency rates become questionable. Nevertheless this study highlights the importance of doing a randomized control trial targeting a specific lesion. In a controlled pilot study of radio-cephalic AVF with inflow stenosis Lai et al from Taiwan showed short term patency benefits with DEB angioplasty as compared to standard PBA. This being a pilot study had only 20 patients and was not adequately powered to answer the question. If these results are indeed proven to be true, this can lead to great improvement in patency of AVF's. In a randomized control trial the researchers are planning to assess the efficacy of DEB angioplasty as compared to standard PBA in AVF's with EFF.

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11211
        • Recruiting
        • King Faisal Specialist Hospital & Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Age >18 years
  • Patients with EFF
  • Stenosis anywhere in the AVF being the only identifiable cause of EFF.

Exclusion Criteria:

  • Patients with AVF which is deeper than 0.8cm from the skin.
  • AVF which is tortuous and lacks adequate straight segment for cannulation with 2 needles.
  • Patients with allergy to paclitaxel
  • Patients on anti-coagulation and those with bleeding disorders.
  • Severe thrombocytopenia i.e platelet count< 50,000.
  • Life expectancy less than 12 months.
  • Documented severe contrast allergy.
  • Inability to come for timely and adequate follow up.
  • Patients undergoing transplantation work up and expected to be transplanted within 6 months.
  • EFF secondary to accessory veins or causes other than stenosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug Eluting Balloon
After pre dilation of the lesion with regular angioplasty balloon, drug coated balloon Lutonix(R) by Bard Inc. will be introduced over the lesion as quickly as possible. Lutonix is a paclitaxel coated balloon which delivers the drug locally. The diameter of the drug coated balloon will be same as the diameter of the largest balloon used for pre dilation. Drug coated balloon will be inflated not exceeding the rated burst pressure. The minimum inflation time will be 1 minute.
Drug: Drug Eluting Balloon
After pre dilation of the lesion with regular angioplasty balloon, drug coated balloon Lutonix(R) by Bard Inc. will be introduced over the lesion as quickly as possible. Lutonix is a paclitaxel coated balloon which delivers the drug locally. The diameter of the drug coated balloon will be same as the diameter of the largest balloon used for pre dilation. Drug coated balloon will be inflated not exceeding the rated burst pressure. The minimum inflation time will be 1 minute.
Other Names:
  • Lutonix drug eluting Balloon angioplasty
Sham Comparator: Regular Angioplasty
After predilation of the lesion with regular balloon, the same balloon will be reintroduced without the drug to be inflated for a minimum of 1 minute. This angioplasty will not deliver any local drug.
Procedure: Regular angioplasty
After predilation of the lesion with regular balloon, the same balloon will be reintroduced without the drug to be inflated for a minimum of 1 minute. This angioplasty will not deliver any local drug.
Other Names:
  • Percutaneous balloon angioplasty

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary patency
Time Frame: 6 months
Patency of AVF without any additional procedures. Patency is defined as supporting HD with a pump speed of at least 300ml/min.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Patency
Time Frame: 6 months
Patency of AVF with additional procedures.Patency is defined as supporting HD with a pump speed of at least 300ml/min.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King Faisal Specialist Hospital & Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Anticipated)

September 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

December 15, 2015

First Submitted That Met QC Criteria

December 15, 2015

First Posted (Estimate)

December 17, 2015

Study Record Updates

Last Update Posted (Estimate)

October 4, 2016

Last Update Submitted That Met QC Criteria

October 3, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2151 054

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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