The Use of Glyceryl Trinitrate Patches in Arteriovenous Fistulas

The aim of the study is to determine whether the application of a glyceryl trinitrate patch (GTN patch) helps arteriovenous fistulas, created for renal dialysis access, mature so that they can be used.

Study Overview

• Status: Completed
• Conditions: Renal Failure
• Intervention / Treatment: Drug: GTN patch; Drug: placebo comparator

Detailed Description

Patients with end stage renal failure on haemodialysis must have a mechanism for achieving access to their vascular system for dialysis. Arteriovenous fistulas (surgically created connections between the artery and vein) are critical for the majority of patients. Not all the fistulas that are created work, a proportion fail early on and need to be revised or an alternative fistula created. A recent multicentre study demonstrated a 40% primary failure rate(1). In an attempt to increase the numbers of fistulae that reach maturation sufficient for dialysis access cannulation some renal centres apply GTN patches to the fistula at the time of surgery. It is thought that this works by increasing the size of the blood vessels and promoting blood flow through them and some preliminary work seems to support this(2).

The evidence for the use of GTN patches in arteriovenous fistula creation is theoretical or based on preliminary work rather than robust evidence. Similarly no evidence exists within the literature to determine the safety and definite efficacy of this procedure in this population. We propose to conduct a double-blinded randomised control trial to answer the study question: does the application of a GTN patch increase the venous outflow diameter post fistula formation and does this result in improved fistula patency.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital, Birmingham.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary arteriovenous fistulas

  • Brachiocephalic
  • Radiocephalic (both proximal and distal)
• >18 yrs old
• Diabetics and smokers will be eligible for inclusion

Exclusion Criteria:

• All complex vascular access procedures

  • Re-do brachiocephalic and radiocephalic fistulas
  • Brachiobasilic fistulas
  • Prosthetic grafts

• Cardiovascular dysfunction

  • Hypotension (systolic <90)
  • Obstructive Cardiomyopathy
  • Severe Aortic stenosis (gradient >40mmhg)
  • Confirmed myocardial infarction within the last 6 months
• Marked anaemia (Hb<8)
• Migraine

• Medications

  • Sildenafil
  • Pre-existing nitrate use
• Nitrate allergy
• Closed-angle glaucoma
• Chronically raised intra-cranial pressure
• History of hypothyroid disease
• < 18 years old

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GTN patch; GTN patch 5mg, in situ 24hrs	Drug: GTN patch; Other Names: Minitran 5
Placebo Comparator: Placebo patch; Placebo patch, in situ for 24hrs	Drug: placebo comparator; This arm will be a placebo patch to the active drug patch to blind the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change to diameter of vein	At initial assessment of the vein the size will be recorded for later comparison. This will then be re-assessed at 6 weeks post-surgery to allow the change in venous diameter to be assessed.	Initial assessment and 6 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	Those receiving the active patch will be compared with those receiving the placebo patch for adverse events	6 weeks

Collaborators and Investigators

• Sponsor: University Hospital Birmingham
• Investigators: Principal Investigator: Nicholas G Inston, FRCS, University Hospital Birmingham, UK.

Publications and helpful links

General Publications

• Huijbregts HJ, Bots ML, Wittens CH, Schrama YC, Moll FL, Blankestijn PJ; CIMINO study group. Hemodialysis arteriovenous fistula patency revisited: results of a prospective, multicenter initiative. Clin J Am Soc Nephrol. 2008 May;3(3):714-9. doi: 10.2215/CJN.02950707. Epub 2008 Feb 6.
• Akin EB, Topcu O, Ozcan H, Ersoz S, Aytac S, Anadol E. Hemodynamic effect of transdermal glyceryl trinitrate on newly constructed arteriovenous fistula. World J Surg. 2002 Oct;26(10):1256-9. doi: 10.1007/s00268-002-6515-1. Epub 2002 Sep 4.
• Field M, McGrogan D, Marie Y, Joinson M, Andujar C, Dutton M, Krishnan H, Hodson J, van Dellen D, Inston NG. Randomized clinical trial of the use of glyceryl trinitrate patches to aid arteriovenous fistula maturation. Br J Surg. 2016 Sep;103(10):1269-75. doi: 10.1002/bjs.10217. Epub 2016 Jul 29.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimate): September 14, 2012

Study Record Updates

• Last Update Posted (Estimate): June 2, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Arteriovenous fistula; Patency; GTN patch
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Fistula; Arteriovenous Fistula
• Other Study ID Numbers: RRK4178