Clinical trial NCT00379366: External Ionizing Radiation to Prevent Restenosis on Haemodialysis Vascular Access
Official title: Efficacy and Tolerance of Transcutaneous Ionizing Radiations to Prevent Restenosis Caused by Intimal Hyperplasia on Prosthetic Haemodialysis Vascular Access
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Renal Insufficiency, Chronic
Graft Occlusion, Vascular
Thrombosis
Intimal Hyperplasia
Keywords: Randomized Controlled Trials
Renal Dialysis
Graft Occlusion, Vascular
Angioplasty
Vascular Patency
Radiation, Ionizing
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2006-09-21
Enrollment: 5
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: Although ionizing radiations have been proposed for the prevention of intimal hyperplasia in coronary and peripheral arteries, information is lacking on how irradiation may prevent neointimal smooth-muscle cell proliferation and restenosis on prosthetic haemodialysis vascular access. We will assess the preventive effect of one dose of radiations (14 Gy) administered transcutaneously one day after dilatation of stenosis on prosthetic haemodialysis vascular access in a randomized controlled trial with a standardized clinical and ultrasonographic one-year follow-up.

Detailed description: Background: one of the major clinical concerns of prosthetic haemodialysis access is the risk of possible restenosis after stenosis dilatation. Only 25% of dilated prosthetic haemodialysis vascular accesses remain patent at one year. No available pharmacological agents can yet effectively prevent it. After stenosis dilatation the vascular wall responds to mechanical injury in a standardized manner: intimal smooth-muscle cells migrate and proliferate, a neointima gradually begins to form and the cell phenotype changes from contractile to secretory. One way to inhibit the neointimal proliferation responsible for restenosis is to induce cell apoptosis by delivering ionizing radiations to the dilated area after the endovascular procedure. Experimental studies and multicenter clinical trials have reported the beneficial effects of endovascular beta or gamma ionizing radiation on vascular restenosis. Experimental studies in animals and recent clinical trials clearly show that external irradiation also reduces neointimal proliferation after arterial injury thus opening the way for the clinical assessment of ionizing radiations on arteries. In a previous experimental study, we reported that irradiation has a dose-dependent effect on the prevention of restenosis: a dose larger than 10 Gy is needed to obtain a significant reduction of intimal hyperplasia.

Objective: the main objective is to assess external ionizing radiation for restenosis prevention on prosthetic haemodialysis vascular accesses after angioplasty. A secondary objective is to assess the treatment safety.

Methods: Single blind randomized clinical trial on two parallel groups of 53 patients each. Patients with chronic renal failure treated by dialysis will be included after a successful angioplasty on a stenosis of the vein adjacent to their prosthetic haemodialysis vascular access. One group will be treated by a single dose of ionizing radiations (14 Gy) at day 1 after angioplasty. The control group will not receive any preventive treatment. The primary outcome is the one-year vascular access patency failure. Secondary outcomes are the one-year delay of occurrence of a restenosis and the treatment safety. Outcomes will be assessed by a clinical and ultrasonographic (at 1, 3, 6 and 12 months, or at other time points in case of stenosis suspicion) follow-up.

Eligibility criteria: Inclusion Criteria:

* over 18 years
* successful angioplasty (residual stenosis \< 30%) on a significant stenosis (maximal systolic speed 3 times \> from basal maximal systolic speed, stenosis \> 70% on angiography) on the venous-prosthesis anastomosis or on the venous segment 5 cm after the anastomosis of a prosthetic haemodialysis vascular access (at least 1 month old)
* social security affiliation
* signed informed consent

Exclusion Criteria:

* contra-indications of radiotherapy
* angioplasty with stenting

Primary outcomes:
measure: Thrombosis or stenosis > to 70% or indication of a new treatment of stenosis during the 12 month follow-up
timeFrame: 1, 3, 6 and 12 month after initial angioplasty
Secondary outcomes:
measure: Stenosis (> to 70%) or thrombosis or indication of a new treatment occurring
timeFrame: 1, 3, 6 or 12 months after initial angioplasty
measure: safety
timeFrame: 1, 3, 6 and months after initial angioplasty
Other outcomes:
Locations:
city: Bayonne
country: France
facility: Clinc Delay
city: Bayonne
country: France
facility: Côte Basque Hospital
city: Bordeaux cedex
country: France
facility: Service de Chirurgie Vasculaire, Hôpital Pellegrin-tripode, CHU de Bordeaux
city: Bordeaux
country: France
facility: Clinic Saint Augustin
city: Perigueux
country: France
facility: Clinic Francheville
Study officials:
affiliation: University Hospital, Bordeaux, France
name: Jean-Philippe MAIRE, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux, France
name: Paul Perez, Dr
role: STUDY_CHAIR
References: