Condition category
Circulatory System
Date applied
28/10/2015
Date assigned
28/10/2015
Last edited
16/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic kidney disease (CKD) is a long-term condition where the kidneys do not work properly. In a healthy person, the kidneys are vital for filtering out the waste products and excess water in the blood, and converting them into urine. In patients suffering from CKD, the kidneys are unable to do this, and so the body is unable to get rid of the waste products building up in the blood. Haemodialysis is one of the most common treatments for CKD patients, and involves diverting the blood into an external machine so that it can be “cleaned”, before being returned to the body. Haemodialysis requires direct access to the circulatory system (blood stream) and the best option for this is a by creating an arteriovenous fistula (AVF), which is made by surgically joining an artery and a vein in the arm. AVFs have a limited lifespan, and over time become narrowed (stenosed) or blocked (thrombosed). This can lead to a patient being admitted to hospital to have emergency lines fitted in their neck, which can cause infection. The fistula can be used for haemodialysis again if it is “re-opened”. This is done by inflating a small balloon inside the fistula to flatten any blockages against the artery wall (fistuloplasty). In many cases however, the narrowing (stenosis) can return, re-blocking the fistula. Studies have shown that in the legs and heart, using a balloon coated with certain drugs, such as paclitaxel, can prevent cells from multiplying and re-blocking the artery. The aim of this study is to find out whether using paclitaxel coating balloons in a fistuloplasty procedure can help to prevent later AVF stenosis.

Who can participate?
Adults who have a narrowed AVF, which has been used for haemodialysis at least 12 times.

What does the study involve?
Participants are randomly allocated to one of two groups. Both groups receive the standard fistuloplasty procedure, in which a plain balloon is inflated until the fistula becomes wide enough to become usable. Those in the first group then receive a second fistuloplasty with a balloon coated in a drug called paclitaxel, which is inserted and inflated until it touches the wall of the blood vessel and transfers the paclitaxel onto the blood vessel wall. Those in the second group receive a second fistuloplasty with a balloon which is not drug coated. Participants attend regular follow-up appointments so that the openness (patency) of the fistula can be monitored.

What are the possible benefits and risks of participating?
Participants who receive the drug coated balloon treatment may have the chance of a better outcome for their fistula. Risks of participating are minimal, however the fistuloplasty procedure may be uncomfortable and cause pain.

Where is the study run from?
Guy's Hospital, London (lead centre) and five other NHS hospitals in England (UK)

When is the study starting and how long is it expected to run for?
November 2015 to November 2017

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Mrs Vikki Semik

Trial website

Contact information

Type

Public

Primary contact

Mrs Vikki Semik

ORCID ID

Contact details

MRC Centre for Transplantation
Dept. of Nephrology and Transplantation
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

20038

Study information

Scientific title

Paclitaxel assisted balloon Angioplasty of Venous stenosis in haEmodialysis access: The PAVE trial. A multicentre double-blind randomised controlled trial in haemodialysis patients with a stenosis in a native arteriovenous fistula

Acronym

PAVE

Study hypothesis

The aim of this study is to compare the efficacy of additional paclitaxel-coated balloon fistuloplasty to plain balloon fistuloplasty only to preserve the patency of arteriovenous fistulae used for haemodialysis.

Ethics approval

London - Chelsea Research Ethics Committee, 12/05/2015, ref: 15/LO/0638

Study design

Double-blind multicentre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Renal disorders; Subtopic: Renal disorders; Disease: All Renal disorders

Intervention

Participants are randomised into one of two arms.

Intervention arm: Participants will receive standard-of-care fistuloplasty with a plain balloon, followed directly by insertion of a paclitaxel-coated balloon.
Control arm: An identical procedure is followed, but using a placebo balloon that is not drug coated.

Follow-up for both trial arms is every 3 months post-treatment. Participants in both trial arms who have not reached the primary outcome measure at 6 months post-recruitment will be invited to undergo a protocol fistulogram. Follow-up length is variable, and between 1 and 3 years; follow-up will end when the last recruited participant has been followed for 1 year.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Time to end of target lesion primary patency* is determined through AVF imaging when patient is referred for a re-intervention, at any point during follow-up (1-3 years).

*Primary patency fails when any of the following occur:
1. Clinically driven re-intervention to the treatment segment
2. Thrombotic occlusion that includes the treatment segment
3. Surgical intervention that excludes the treatment segment from the access circuit
4. Abandonment of the AVF due to an inability to retreat the treatment segment

Secondary outcome measures

1. Angiographically determined late lumen loss; measured on a protocol fistulogram at 6 months by an independent core laboratory
2. The rate of angiographic binary re-stenosis; measured on a protocol fistulogram at 6 months by an independent core laboratory
3. Time to end of access circuit primary patency* measured at a referred re-intervention, at any point during follow-up (1-3 years)
4. Time to end of access circuit cumulative patency (when the AVF is abandoned, regardless of radiological or surgical intervention, with or without a thrombosis event) measured at a referred re-intervention, at any point during follow-up (1-3 years)
5. Procedural success determined by measuring residual stenosis (≤ 30%) on post-procedure fistulogram, after treatment fistuloplasty
6. Number of thrombosis events measured at end of follow-up (1-3 years)
7. Total number of interventions measured at end of follow-up (1-3 years)
8. Adverse events (e.g. fistula rupture, infection) measured at end of follow-up (1-3 years)
9. Patient quality of life measured using the EuroQuol EQ-5D generic health survey, and the disease specific Patient (or Palliative care) Outcome Scale symptom score-renal (POS-S Renal) at baseline, 6, and 12 months

*Ends when any of the following occur:
1. Access circuit thrombosis
2. An intervention (either radiological or surgical) anywhere in the access circuit
3. The access circuit is abandoned due to an inability to treat any lesion

Overall trial start date

01/05/2015

Overall trial end date

30/04/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients (18 years or over) who have a native AVF in the arm that has been used for at least 12 consecutive dialysis sessions
2. An indication for a fistuloplasty as determined by the local clinical team
3. The access circuit is free of synthetic graft material or stents
4. A reduction of vessel diameter of greater than or equal to 50%, and a reference diameter of the outflow vein of at least 4 mm and less that the diameter of the largest available paclitaxel-coated balloon
5. A residual stenosis of 30% after plain balloon fistuloplasty

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 211; UK Sample Size: 211

Participant exclusion criteria

1. Patient unable to give informed consent
2. Patient unwilling or unable to comply with all study­related procedures
3. Systemic or local (to the fistula) infection treated for less than 10 days prior to the study procedure
4. Synchronous venous lesion, with a reduction of vessel diameter of greater than or equal to 50% measured angiographically, in the same access circuit
5. Location of stenosis beyond the thoracic inlet
6. Thrombosed (failed) dialysis circuit at time of treatment
7. Women who are breastfeeding, pregnant or are intending to become pregnant or men intending to father children, within two years of study treatment
8. Known hypersensitivity or contraindication to contrast medium which cannot be adequately pre­-medicated
9. Known hypersensitivity or contraindication to paclitaxel

Recruitment start date

29/10/2015

Recruitment end date

31/10/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy's Hospital
Guy’s and St Thomas’ NHS Foundation Trust Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

King’s College Hospital
King’s College Hospital NHS Foundation Trust Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Royal Free Hospital
Royal Free London NHS Foundation Trust Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Lister Hospital
East and North Hertfordshire NHS Trust Chelsea Bridge Road
London
SW1W 8RH
United Kingdom

Trial participating centre

Kent and Canterbury Hospital
East Kent Hospitals University NHS Foundation Trust Ethelbert Road
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Brighton and Sussex University Hospitals NHS Trust Eastern Road
Brighton
BN2 5BE
United Kingdom

Sponsor information

Organisation

Kings College London

Sponsor details

MRC Centre for Transplantation
Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.kcl.ac.uk

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The results of this project will be communicated to the research community through clinical and scientific national and international meetings. The findings are likely to be presented as oral presentations and published as abstracts on the relevant organisation's website. The formal result of the clinical trial will be published in a scientific journal.

Intention to publish date

14/05/2019

Participant level data

Available on request

Results - basic reporting

Publication summary

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27175481

Publication citations

Additional files

Editorial Notes

16/05/2016: Publication reference added.