Clinical trial NCT06679907: Medico-economic Evaluation of the Creation of Arteriovenous Access for Hemodialysis Between Surgical Technique and Endovascular Technique in Patients with End-stage Renal Disease
Official title: Cost-effectiveness Study Comparing Endovascular and Surgical Arteriovenous Fistula Creation for Haemodialysis in Patients with End-stage Renal Failure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Endovascular Procedure
Hemodialysis
Keywords: Hemodialysis
arteriovenous
endovascular
restenosis
cost-effectiveness
health economic evaluation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2024-11-08
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic, comparative, unblinded, randomized, controlled, prospective, parallel-arm multicenter superiority clinical trial
Primary purpose: TREATMENT

Brief summary: This multicenter 1 :1 randomized controlled trial aims at comparing the cost-effectiveness of endovascular arteriovenous fistula (AVF) creation using Ellipsys® and WaveLinQ® devices with traditional surgical AVF creation for hemodialysis. The primary endpoint is the cost-utility ratio (cost per QALY gained), with an anticipated sample size of 252 patients. This study will provide critical insights into the viability and cost-effectiveness of endovascular techniques, potentially shaping future standards of care in hemodialysis access.

Detailed description: Chronic kidney disease (CKD) is a global public health issue, affecting approximately 10% of the population.1,2 The number of patients starting renal replacement therapy has grown exponentially in recent years.3 Effective hemodialysis relies on a well-functioning vascular access (VA). The Kidney Disease Outcome Quality Initiative (KDOQI)4, the French Health Authority (HAS)5, and the European Society of Vascular and Endovascular Surgery (ESVS)6 recommend native arteriovenous fistulas (AVFs) as a primary option, referring to their lower morbidity, reduced mortality, and improved quality of life.7,8 An ideal AVF should allow cannulation with two needles, provide a blood flow of 300 to 600ml/min, resist infection and thrombosis, and have minimal adverse events.6 Between 2005 and 2007, 67-91% of patients in France used native AVFs.7 Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed that AVF maturation varies significantly by country, patient and center characteristics. In Japan, 84% of AVFs were created in the forearm, compared to 54% in EUR/ANZ (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New Zealand), and 32% in the United States (US).9 Catheter-dependence following AVF creation remained high in EUR/ANZ and US patients, with nearly 70% still dependent 8 months after AVF creation. Failure to use AVFs within 6 months was associated to a 53% higher mortality rate in the following 6 months.9 A systematic review and meta-analysis of 318 studies10 reported that average AVF primary, assisted primary and secondary patency rates at one year were 64%, 73% and 79%, respectively. However, not all patent AVFs were suitable for dialysis: only 26% were mature at 6 months, and 21% were abandoned without ever being used.

Furthermore, up to 85% of AVFs require multiple re-interventions, including angioplasty, stenting, transposition, thrombectomy or thrombolysis within the first year.11-13 On average, up to 3.43 reinterventions per patient were required over the study duration, with higher rates for brachio-basilic accesses, contributing significantly to the overall cost of care.11-13 To improve outcomes, endovascular AVF creation techniques have been developed.14 These methods use radiofrequency or thermo-coagulation energy, guided by fluoroscopy and/or duplex ultrasound. Avoiding vessel dissection and mobilization, while minimizing trauma to the vascular wall and surrounding tissues, may help reduce the risk of intimal hyperplasia and AVF failure. This approach could lead to similar benefits as those demonstrated by surgical no-touch techniques.15 Preliminary results show a technical success rate of 97.5%, a 3-month maturation rate of 89.3%, a 1-year patency rate of 85.7%, and an average of 0.59 reinterventions per patient per year.16-19 As a results, data from the United States Renal Data System (USRDS) were compared to data from the Novel Endovascular Access Trial (NEAT) and both incident and prevalent patients with endoAVF required fewer interventions and had lower costs within the first year compared with matched patients with surgical AVFs.20 However, these devices are expensive (approximately €5,200 per patient) and the creation of an endovenous fistula is not yet listed in France's common classification of medical procedures (CCAM), making it ineligible for reimbursement by health insurance.21,22 In 2019, there were 15,653 hospitalizations in France for AVF creation and re-interventions to aid AVF maturation or restore patency in patients with end-stage renal disease. Although international studies suggest that endovascular AVF creation is effective,18,20,23 no French studies have yet replicated or confirmed these findings in the local context to support reimbursement claims. The 2018 ESVS guidelines also cite a lack of evidence on endovascular AVF creation.6 This protocol represents the first French medico-economic study to compare the two available endovascular AVF creation devices - Ellipsys® (Medtronic, Dublin, Ireland) and WaveLinQ® (BD, Bard, Franklin Lakes, New Jersey, United States of America) - with traditional open surgery. This randomized clinical trial aims to provide crucial data for healthcare decision-makers, potentially paving the way for the adoption of these devices in France, enhancing patient care, and improving quality of life.

Eligibility criteria: Inclusion Criteria:

Patients:

* Age\> 18 years
* On chronic dialysis, or due to start chronic dialysis within 3 to 6 months
* Patient eligible for the creation of a native surgical AVF at the elbow crease and an endovenous AVF according to the instructions for use of the manufacturers of the two devices used, namely:
* Target venous diameter for fistula creation \> or = 3 mm
* Target arterial diameter for fistula creation \> or = 2 mm
* Artery to vein distance \< or = 1.5mm
* At least one superficial outflow vein with a diameter ≥ 2.5 mm connected via a proximal forearm perforating vein with the target site
* Patency of the radial and ulnar arteries confirmed by Doppler ultrasound
* Presence of a connecting perforator between the deep and superficial venous network, relatively straight anatomy
* Distance between proximal radial artery and perforator junction/radial vein \< 1.5mm
* Patient having been clearly informed about the study and having agreed to participate and attend follow-up visits
* Patient affiliated or beneficiary of a social security scheme.

Exclusion Criteria:

* Known central venous stenosis \> 50% on imaging or presence of an indwelling central venous catheter or pacemaker on the same side as the side of creation of the AVF
* Upper extremity arterial occlusive disease not amenable to endovascular or open repair
* Eligibility for a native distal AVF (radio or ulno-cephalic)
* New York Heart Association (NYHA) class III or IV heart failure
* Hypercoagulable state
* Estimated life expectancy \<1 year
* Pregnantly or breastfeeding woman
* Known allergies to medical devices and medications used in the protocol
* Inability to collect consent
* Patient not affiliated to a social security scheme

Primary outcomes:
measure: Cost-utility differential ratio (expressed as cost per Quality-Adjusted Life Year [QALY]) with endovascular AVF vs. open surgery
timeFrame: month 18
Secondary outcomes:
measure: Evaluation of total cost of care for endovascular
timeFrame: Month 18
measure: Real costs of initial hospitalization for endovascular AVF vs. surgical AVF creation
timeFrame: Day 0
measure: Evaluation of total cost of care for surgical AVF creation
timeFrame: Month 18
measure: Evaluation of total cost of care for endovascular
timeFrame: Month 36
measure: Evaluation of total cost of care for surgical AVF creation
timeFrame: Month 36
measure: Evaluation of cost functional AVF without reintervention
timeFrame: Month 36
measure: Evaluation of cost with adoption of endovascular AVF
timeFrame: 5 years
measure: Evaluation of frequency of reinterventions for vascular access
timeFrame: Month 36
measure: Number of AVF creation success
timeFrame: Day 0
measure: Number of mature AVFs
timeFrame: Month 6
measure: Number of mature AVFs
timeFrame: Month 12
measure: Number of mature AVFs
timeFrame: Month 18
measure: Evaluation of time to maturation
timeFrame: Month 6
measure: Evaluation of time to maturation
timeFrame: Month 18
measure: Evaluation of time to maturation
timeFrame: Month 12
measure: Number of Functional AVFs
timeFrame: Month 6
measure: Number of Functional AVFs
timeFrame: Month 12
measure: Number of Functional AVFs
timeFrame: Month 18
measure: Number of recirculation
timeFrame: Month 6
measure: Number of recirculation
timeFrame: Month 12
measure: Number of recirculation
timeFrame: Month 18
measure: Number of days hospitalised for AVF creation
timeFrame: Day 15
measure: Number of adverse events related to vascular access
timeFrame: Day 1
measure: Number of adverse events related to vascular access
timeFrame: Month 1
measure: Number of adverse events related to vascular access
timeFrame: Month 6
measure: Number of adverse events related to vascular access
timeFrame: Month 12
measure: Number of adverse events related to vascular access
timeFrame: Month 18
measure: Number of serious adverse events related to AVF device
timeFrame: Day 0
measure: Number of serious adverse events related to AVF device
timeFrame: Month 1
measure: Number of serious adverse events related to AVF device
timeFrame: Month 6
measure: Number of serious adverse events related to AVF device
timeFrame: Month 12
measure: Number of serious adverse events related to AVF device
timeFrame: Month 18
measure: Number of serious adverse events related to AVF device
timeFrame: Month 36
measure: Number of Reinterventions related to AVF device
timeFrame: Day 0
measure: Number of Reinterventions related to AVF device
timeFrame: Month 1
measure: Number of Reinterventions related to AVF device
timeFrame: Month 6
measure: Number of Reinterventions related to AVF device
timeFrame: Month 12
measure: Number of Reinterventions related to AVF device
timeFrame: Month 18
measure: Number of Reinterventions related to AVF device
timeFrame: Month 36
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine - Centre Aquitain des pathologies vasculaire
city: Boulogne-billancourt
country: France
facility: AP-HP Centre Hospitalier Universitaire d'Ambroise Paré
city: Castelnau-le-Lez
country: France
facility: Clinique du parc
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon - Hôpital le Bocage
city: Grenoble
country: France
facility: Centre Hospitalier Mutualiste de Grenoble
city: Lyon
country: France
facility: Hôpital privé Jean Mermoz
city: Lyon
country: France
facility: Centre Hospitalier St Joseph - St Luc
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hôpital Pasteur 1
city: Paris
country: France
facility: Groupe Hospitalier Paris St Joseph - Centre Hospitalier Chartres
city: Saint-herblain
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôpital Nord Laennec
Study officials:
References:
citation: Jones RG, Morgan RA. A Review of the Current Status of Percutaneous Endovascular Arteriovenous Fistula Creation for Haemodialysis Access. Cardiovasc Intervent Radiol. 2019 Jan;42(1):1-9. doi: 10.1007/s00270-018-2037-6. Epub 2018 Jul 20.
citation: Arnold RJG, Han Y, Balakrishnan R, Layton A, Lok CE, Glickman M, Rajan DK. Comparison between Surgical and Endovascular Hemodialysis Arteriovenous Fistula Interventions and Associated Costs. J Vasc Interv Radiol. 2018 Nov;29(11):1558-1566.e2. doi: 10.1016/j.jvir.2018.05.014. Epub 2018 Oct 5.
citation: Shahverdyan R, Beathard G, Mushtaq N, Litchfield TF, Nelson PR, Jennings WC. Comparison of Outcomes of Percutaneous Arteriovenous Fistulae Creation by Ellipsys and WavelinQ Devices. J Vasc Interv Radiol. 2020 Sep;31(9):1365-1372. doi: 10.1016/j.jvir.2020.06.008. Epub 2020 Aug 11.
citation: Mallios A, Bourquelot P, Franco G, Hebibi H, Fonkoua H, Allouache M, Costanzo A, de Blic R, Harika G, Boura B, Jennings WC. Midterm results of percutaneous arteriovenous fistula creation with the Ellipsys Vascular Access System, technical recommendations, and an algorithm for maintenance. J Vasc Surg. 2020 Dec;72(6):2097-2106. doi: 10.1016/j.jvs.2020.02.048. Epub 2020 Apr 8.
citation: Hull J, Deitrick J, Groome K. Maturation for Hemodialysis in the Ellipsys Post-Market Registry. J Vasc Interv Radiol. 2020 Sep;31(9):1373-1381. doi: 10.1016/j.jvir.2020.03.001. Epub 2020 Aug 14.
citation: Mallios A, Jennings WC, Boura B, Costanzo A, Bourquelot P, Combes M. Early results of percutaneous arteriovenous fistula creation with the Ellipsys Vascular Access System. J Vasc Surg. 2018 Oct;68(4):1150-1156. doi: 10.1016/j.jvs.2018.01.036. Epub 2018 Apr 19.
citation: Bhojani MF, Malik J, Mumtaz A, Sophie Z, Waseem S. Beyond Conventional: A Systematic Review of Non-Conventional Techniques for Radio-Cephalic Arteriovenous Fistula. Ann Vasc Surg. 2025 Jan;110(Pt B):306-316. doi: 10.1016/j.avsg.2024.07.091. Epub 2024 Aug 7.
citation: Rajan DK, Lok CE. Promises for the future: minimally invasive fistula creation. J Vasc Access. 2015;16 Suppl 9:S40-1. doi: 10.5301/jva.5000351. Epub 2015 Mar 8.
citation: Palmes D, Kebschull L, Schaefer RM, Pelster F, Konner K. Perforating vein fistula is superior to forearm fistula in elderly haemodialysis patients with diabetes and arterial hypertension. Nephrol Dial Transplant. 2011 Oct;26(10):3309-14. doi: 10.1093/ndt/gfr004. Epub 2011 Feb 16.
citation: Koksoy C, Demirci RK, Balci D, Solak T, Kose SK. Brachiobasilic versus brachiocephalic arteriovenous fistula: a prospective randomized study. J Vasc Surg. 2009 Jan;49(1):171-177.e5. doi: 10.1016/j.jvs.2008.08.002. Epub 2008 Oct 22.
citation: Woo K, Farber A, Doros G, Killeen K, Kohanzadeh S. Evaluation of the efficacy of the transposed upper arm arteriovenous fistula: a single institutional review of 190 basilic and cephalic vein transposition procedures. J Vasc Surg. 2007 Jul;46(1):94-99; discussion 100. doi: 10.1016/j.jvs.2007.02.057. Epub 2007 Jun 1.
citation: Bylsma LC, Gage SM, Reichert H, Dahl SLM, Lawson JH. Arteriovenous Fistulae for Haemodialysis: A Systematic Review and Meta-analysis of Efficacy and Safety Outcomes. Eur J Vasc Endovasc Surg. 2017 Oct;54(4):513-522. doi: 10.1016/j.ejvs.2017.06.024. Epub 2017 Aug 23.
citation: Pisoni RL, Zepel L, Zhao J, Burke S, Lok CE, Woodside KJ, Wasse H, Kawanishi H, Schaubel DE, Zee J, Robinson BM. International Comparisons of Native Arteriovenous Fistula Patency and Time to Becoming Catheter-Free: Findings From the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2021 Feb;77(2):245-254. doi: 10.1053/j.ajkd.2020.06.020. Epub 2020 Sep 21.
citation: Ravani P, Palmer SC, Oliver MJ, Quinn RR, MacRae JM, Tai DJ, Pannu NI, Thomas C, Hemmelgarn BR, Craig JC, Manns B, Tonelli M, Strippoli GF, James MT. Associations between hemodialysis access type and clinical outcomes: a systematic review. J Am Soc Nephrol. 2013 Feb;24(3):465-73. doi: 10.1681/ASN.2012070643. Epub 2013 Feb 21.
citation: Ethier J, Mendelssohn DC, Elder SJ, Hasegawa T, Akizawa T, Akiba T, Canaud BJ, Pisoni RL. Vascular access use and outcomes: an international perspective from the Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant. 2008 Oct;23(10):3219-26. doi: 10.1093/ndt/gfn261. Epub 2008 May 29.
citation: Schmidli J, Widmer MK, Basile C, de Donato G, Gallieni M, Gibbons CP, Haage P, Hamilton G, Hedin U, Kamper L, Lazarides MK, Lindsey B, Mestres G, Pegoraro M, Roy J, Setacci C, Shemesh D, Tordoir JHM, van Loon M, Esvs Guidelines Committee, Kolh P, de Borst GJ, Chakfe N, Debus S, Hinchliffe R, Kakkos S, Koncar I, Lindholt J, Naylor R, Vega de Ceniga M, Vermassen F, Verzini F, Esvs Guidelines Reviewers, Mohaupt M, Ricco JB, Roca-Tey R. Editor's Choice - Vascular Access: 2018 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018 Jun;55(6):757-818. doi: 10.1016/j.ejvs.2018.02.001. Epub 2018 May 2. No abstract available.
citation: Erratum Regarding "KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update" (Am J Kidney Dis. 2020;75[4][suppl 2]:S1-S164). Am J Kidney Dis. 2021 Apr;77(4):551. doi: 10.1053/j.ajkd.2021.02.002. No abstract available.
citation: Port FK. End-stage renal disease: magnitude of the problem, prognosis of future trends and possible solutions. Kidney Int Suppl. 1995 Aug;50:S3-6.
citation: Wetzels JF, Kiemeney LA, Swinkels DW, Willems HL, den Heijer M. Age- and gender-specific reference values of estimated GFR in Caucasians: the Nijmegen Biomedical Study. Kidney Int. 2007 Sep;72(5):632-7. doi: 10.1038/sj.ki.5002374. Epub 2007 Jun 13.
citation: Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003 Jan;41(1):1-12. doi: 10.1053/ajkd.2003.50007.