Flow Dysfunction of Hemodialysis Vascular Access

Study Overview
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Brief Summary
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The FLOW trial evaluates the follow-up of the vascular access for hemodialysis. In current clinical care, vascular access flow volume is periodically assessed to detect and treat asymptomatic stenosis. The FLOW trial will determine whether it is safe to abandon this practice of active surveillance. Vascular access stenosis will then be treated only when clinical problems of flow dysfunction occur during hemodialysis. The investigators expect that the intervention rate and medical costs will be reduced by 40% when correction of vascular access stenosis is triggered by clinically apparent access dysfunction rather than asymptomatic flow reduction.

Detailed Description
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Study design: Multicenter randomized controlled trial with 417 patients. Patients will be followed up for 2 to 3 years. The trial is powered to detect a reduction in the intervention rate of 0.25 per year between study groups in a superiority analysis (this is associated with cost savings of 1 million euros per year in the Netherlands). Subgroup analyses of arteriovenous fistulas and grafts and of successful and failed interventions will be done. Study population: Chronic hemodialysis patients with a functioning arteriovenous fistula or graft. Intervention group: Patients are referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present. These include physical signs, problems during dialysis, or an unexplained, sustained fall in dialysis adequacy. Control group: Monthly surveillance of vascular access blood flow volume by ultrasound dilution measurements during hemodialysis sessions. Patients will be referred for correction of the underlying stenosis at an access flow volume <500mL/min, or when clinical signs of flow dysfunction are present.

Official Title
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Flow Dysfunction of Hemodialysis Vascular Access: a Randomized Controlled Trial on the Effectiveness of Surveillance of Arteriovenous Fistulas and Grafts

Conditions
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Dialysis Access Malfunction, Hemodialysis Access Failure, Hemodialysis Fistula Thrombosis, Vascular Access Malfunction

Intervention / Treatment
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* Diagnostic Test: Vascular access monitoring
* Diagnostic Test: Vascular access blood flow measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients aged 18 years or older. End-stage renal disease with unlikely recovery of kidney function according to the attending nephrologist. Arteriovenous fistula or arteriovenous graft as hemodialysis vascular access that fulfills both of the following criteria at the time of trial enrollment: Vascular access flow volume of at least 500mL/min; and Functional vascular access: the vascular access was cannulated with 2 needles and achieved the prescribed access circuit flow in at least 6 dialysis sessions over the past 30 days. Patients who have single needle hemodialysis for reasons other than vascular access dysfunction (e.g. for nocturnal hemodialysis) but who can be cannulated with 2 needles for flow measurements and fulfill the other requirements for a functional vascular access can be enrolled as well. Planning to remain in one of the participating dialysis centers for at least 1 year. Exclusion Criteria: Arteriovenous fistulas with multiple venous outflow paths upstream of the cannulation sites, that are not suitable for flow volume measurements using ultrasound dilution (e.g. Gracz fistulas and Ellipsys or WavelinQ endovascular fistulas). Home hemodialysis. Thrombosis of the current vascular access in the past year. Planned access-related intervention. Living donor kidney transplantation, switch to peritoneal dialysis, or switch to home hemodialysis planned within 6 months. Life expectancy of less than 6 months, in the opinion of the attending nephrologist. Unable to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind randomized controlled trial with hybrid parallel-crossover design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Patients are referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present. These include physical signs, problems during dialysis, or an unexplained, sustained fall in dialysis adequacy. | Diagnostic Test: Vascular access monitoring<br>* Patients are referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present. These include physical signs, problems during dialysis, or an unexplained, sustained fall in dialysis adequacy. Patients will be referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present.<br>|
| Active Comparator: Control group<br>Monthly surveillance of vascular access blood flow volume by ultrasound dilution measurements during hemodialysis sessions. Patients will be referred for correction of the underlying stenosis at an access flow volume <500mL/min, or when clinical signs of flow dysfunction are present. | Diagnostic Test: Vascular access monitoring<br>* Patients are referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present. These include physical signs, problems during dialysis, or an unexplained, sustained fall in dialysis adequacy. Patients will be referred for correction of the underlying stenosis when clinical signs of flow dysfunction are present.<br>Diagnostic Test: Vascular access blood flow measurement<br>* Monthly surveillance of vascular access blood flow volume by ultrasound dilution measurements during hemodialysis sessions. Patients will be referred for correction of the underlying stenosis at an access flow volume <500mL/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Access-related intervention rate | The number of interventions required for each patient-year of hemodialysis treatment | Variable follow-up time of 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Access-related complications per patient-year (1) | Clavien-Dindo grade 2 complications (requiring pharmacological treatment) | Variable follow-up time of 2-3 years | 
| Access-related complications per patient-year (2) | Access-related serious adverse events (Clavien-Dindo grade 4 and 5 complications, and vascular access thrombosis) | Variable follow-up time of 2-3 years | 
| All-cause mortality | All-cause mortality | Variable follow-up time of 2-3 years | 
| Access-related health care costs (1) | Medical Consumption Questionnaire | Every 3 months for 2-3 years from randomization (variable follow-up time) | 
| Access-related health care costs (2) | Productivity Cost Questionnaire | Every 3 months for 2-3 years from randomization (variable follow-up time) | 
| Patient-reported outcome measures (1) | SF-VAQ (Short-Form Vascular Access Questionnaire) | Every 3 months for 2-3 years from randomization (variable follow-up time) | 
| Patient-reported outcome measures (2) | EQ-5D-5L | Every 3 months for 2-3 years from randomization (variable follow-up time) | 
| Quality of the surveillance program (1) | Repeatability and reproducibility of vascular access flow volume measurements | Variable follow-up time of 2-3 years | 
| Quality of the surveillance program (2) | Diagnostic accuracy of vascular access flow volume measurements to predict clinical signs of flow dysfunction and access thrombosis within 1 month in the intervention group | Variable follow-up time of 2-3 years | 
| Quality of the surveillance program (3) | The percentage of vascular access balloon angioplasties resulting in technical success (residual stenosis <30%) and clinical success (increase in flow volume to >500mL/min, restoration of vascular access function and resolution of any clinical signs of flow dysfunction) | Variable follow-up time of 2-3 years | 
| Quality of the surveillance program (4) | Vascular access patency after balloon angioplasty | Variable follow-up time of 2-3 years | 
| Primary patency | This outcome measure will be registered for explanatory analyses | Variable follow-up time of 2-3 years | 
| Assisted primary patency | This outcome measure will be registered for explanatory analyses | Variable follow-up time of 2-3 years | 
| Secondary patency | This outcome measure will be registered for explanatory analyses | Variable follow-up time of 2-3 years | 
| The number of hemodialysis sessions with cannulation difficulties | This outcome measure will be registered for explanatory analyses | Variable follow-up time of 2-3 years |