Clinical trial NCT02913274: Arteriovenous Fistulae: Drug-eluting Balloon Angioplasty
Official title: Fistules Artério-Veineuses: Angioplastie Par Ballon à Elution de Drogue (FAVABED) - Arteriovenous Fistulae: Drug-eluting Balloon Angioplasty
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stenosis of Arteriovenous Dialysis Fistula
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2016-09-23
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Dysfunctions such as tight stenosis or thrombosis in haemodialysis vascular accesses are the leading cause of hospitalisationand morbidity in chronic haemodialysis patients incurring significant related costs estimated at over one billion dollars in the USA.

Dysfunctions of these vascular accesses are generally treated by conventional angioplasty as this is the least invasive procedure, the alternative being revision surgery. Angioplasty uses an inflatable balloon of various diameters. Different types of angioplasty balloons may be needed to break fibrous venous stenosis, in particular high-pressure balloons or cutting balloons. These angioplasty procedures which are often painful during dilation have a high technical success rate but a poor 1-year patency rate.

These invasive repeated procedures impair the quality of life of these patients with end-stage renal disease who are on permanent dialysis or awaiting a kidney transplant and for whom vascular access patency is vital.

Due to their traumatic effect on the vessel wall, these procedures induce cell proliferation processes that retrigger neointimal hyperplasia the very act of preserving the haemodialysis access is the key factor in development of a new stenosis and hence a vicious circle of stenosis-angioplasty.

For the past few years, angioplasty balloons delivering anticancer drugs have been developed. These drugs, generally used in high doses for cancer chemotherapy, are released in small doses on the medical angioplasty devices. During inflation, the local release of the anticancer molecule through the different layers of the vessel wall confers local antiproliferative action without the systemic toxic effects associated with high-dose chemotherapy.

These medical devices have demonstrated their efficacy in terms of increase in primary and secondary patency rates on procedures such as coronary artery angioplasty, femoro-popliteal or sub-popliteal artery angioplasty.

These drug-eluting balloons (DEBs) are also CE marked with the recommendation of being indicated for AVF anticancerangioplasties, but no randomised multi-centre clinical trial has proven their medical effectiveness, and in particular their contribution in terms of patency rate improvement. However, studies on animal models show significant results regarding efficacy against neointimal hyperplasia and the first single-centre clinical trials on a small sample size appear promising.

The key assessment criterion is primary patency of the dilated stenosis at one year defined by patients efficaciously dialysed at one year without re-intervention on the dilated lesion after initial angioplasty. The delay of occurrence of dilation will be considered. Patients that will be non-evaluable for the primary endpointwill be censored at the date of the latest news.

Detailed description: Dysfunctions such as tight stenosis or thrombosis in haemodialysis vascular accesses are the leading cause of hospitalisation (20%) and morbidity in chronic haemodialysis patients incurring significant related costs estimated at over one billion dollars in the USA.

Dysfunctions of these vascular accesses are generally treated by conventional angioplasty as this is the least invasive procedure, the alternative being revision surgery. Angioplasty uses an inflatable balloon of various diameters. Different types of angioplasty balloons may be needed to break fibrous venous stenosis, in particular high-pressure balloons (20 atm) or cutting balloons. These angioplasty procedures which are often painful during dilation have a high technical success rate (90-97%) but a poor 1-year patency rate, varying between 26 and 64% depending on the team and a mean rate estimated at 40% for the studies including the larger number of patients, some of whom requiring several procedures.

These invasive repeated procedures impair the quality of life of these patients with end-stage renal disease who are on permanent dialysis or awaiting a kidney transplant and for whom vascular access patency is vital.

Due to their traumatic effect on the vessel wall, these procedures induce cell proliferation processes that retrigger neointimal hyperplasia the very act of preserving the haemodialysis access is the key factor in development of a new stenosis and hence a vicious circle of stenosis-angioplasty.

For the past few years, angioplasty balloons delivering anticancer drugs (Paclitaxel, Sirolimus, Everolimus) have been developed. These drugs, generally used in high doses for cancer chemotherapy, are released in small doses on the medical angioplasty devices. During inflation, the local release of the anticancer (antimitotic) molecule through the different layers of the vessel wall (Paclitaxel is lipophilic and hydrophobic) confers local antiproliferative action without the systemic toxic effects associated with high-dose chemotherapy.

These medical devices have demonstrated their efficacy in terms of increase in primary and secondary patency rates on procedures such as coronary artery angioplasty, femoro-popliteal or sub-popliteal artery angioplasty (treatment of angina or lower limb arteriopathy).

These drug-eluting balloons (DEBs) are also CE marked with the recommendation of being indicated for AVF anticancerangioplasties, but no randomised multi-centre clinical trial has proven their medical effectiveness, and in particular their contribution in terms of patency rate improvement. However, studies on animal models show significant results regarding efficacy against neointimal hyperplasia and the first single-centre clinical trials on a small sample size appear promising.

The key assessment criterion is primary patency of the dilated stenosis at one year defined by patients efficaciously dialysed at one year without re-intervention on the dilated lesion after initial angioplasty. The delay of occurrence of dilation will be considered (censored criteria). Patients that will be non-evaluable for the primary endpoint (death, lost to follow-up...) will be censored at the date of the latest news.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18,
* Stage 5 renal failure patients on permanent haemodialysis treatment (every 2 or 3 days),
* Native and efficient arteriovenous fistula \> 3 months,
* 3mm ≤ reference vein diameter ≤ 8 mm and stenosis length ≤ 10 cm (range of DEB diameters and lengths),
* Absence of fistula thrombosis,
* Possibility of crossing the stenosis with a guide wire,
* Significant stenosis \> 50% (in relation to the reference diameter) on the fistulogram,
* Clinical diagnosis of imminent fistula dysfunction

  * pressure rise during dialysis
  * and/or puncture difficulties
  * and/or recirculation or poor extrarenal clearance
  * and/or decrease in vascular access flow
  * and/or increase in compression time after dialysis
* Social security affiliation,
* Receipt of free, informed, written consent.

Exclusion Criteria:

* Multiple stenoses,
* Goretex® graft prostheses
* Systemic or local infection,
* Known allergy to contrast agent or Paclitaxel.
* Comorbidity not permitting long-term follow-up,
* Life expectancy \< 1 year,
* Anticancer treatment (patients treated with chemotherapy for neoplasia),
* Pregnant or breastfeeding woman,
* Patients over 18 years of age who are under legal protection (conservatorship, trusteeship, guardianship), or deprived of freedom.

Primary outcomes:
measure: Number of patients whose haemodialysis is efficient at 1 year without needing further treatment of the stenotic site after initial angioplasty
timeFrame: 1 year
Secondary outcomes:
measure: primary patency at 6 months
timeFrame: 6 months
measure: overall primary patency of the Arteriovenous Fistula at 1 year
timeFrame: 1 year
measure: assisted primary patency of the dilated stenosis at 1 year
timeFrame: 1 year
measure: secondary patency of the AVF at 1 year
timeFrame: 1 year
measure: The minimal diameter of the treated stenosis and the AVF flows
timeFrame: 1 year
measure: Overall and cardiovascular survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: Haguenau
country: France
facility: Centre Hospitalier d'Haguenau
city: Marseille
country: France
facility: APHM Hôpital la Timone
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire de Montpellier
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de RENNES
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse
city: Tours
country: France
facility: Clinique St Gatien de Tours
Study officials:
affiliation: Rennes University Hospital
name: Jean-François Heautot, MD
role: PRINCIPAL_INVESTIGATOR
References: