Dialysis Access Malfunction, Hemodialysis Access Failure, Hemodialysis Fistula Thrombosis, Vascular Access Malfunction
Conditions
Brief summary
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
Study design: Multicenter randomized controlled trial with 375 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. On 25-02-2025, the sample size was reduced from 417 to 375 patients because updated calculations based on actual event and loss to follow-up rates in the trial population showed sufficient power to detect the prespecified clinically relevant difference. 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.
Interventions
DIAGNOSTIC_TESTVascular access monitoring
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.
DIAGNOSTIC_TESTVascular access blood flow measurement
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.
Sponsors
Maastricht University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The software of the HD03 Hemodialysis Monitor will be adjusted to allow blinded measurements that will be sent to the trial coordinator; patients and health care providers remain unaware of treatment allocation and surveillance findings. Flow measurements will only be used to refer patients for correction of vascular access stenosis in the control group. To maintain blinding, whenever a measurement must be repeated to confirm low flow volumes, another trial participant will randomly be selected for confirmation of vascular access flow volumes after the next measurement. Patients will be censored and randomized anew following an intervention for flow dysfunction, as soon as the indicator for vascular access intervention has been resolved and vascular access function has been restored.
Intervention model description
Double blind randomized controlled trial with hybrid parallel-crossover design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients aged 18 years or older. 2. End-stage renal disease with unlikely recovery of kidney function according to the attending nephrologist. 3. Arteriovenous fistula or arteriovenous graft as hemodialysis vascular access that fulfills both of the following criteria at the time of trial enrollment: 1. Vascular access flow volume of at least 500mL/min; and 2. 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. 4. Planning to remain in one of the participating dialysis centers for at least 1 year.
Exclusion criteria
1. 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). 2. Home hemodialysis. 3. Thrombosis of the current vascular access in the past year. 4. Planned access-related intervention. 5. Living donor kidney transplantation, switch to peritoneal dialysis, or switch to home hemodialysis planned within 6 months. 6. Life expectancy of less than 6 months, in the opinion of the attending nephrologist. 7. Unable to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Access-related intervention rate | Variable follow-up time of 2-3 years | The number of interventions required for each patient-year of hemodialysis treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Access-related complications per patient-year (1) | Variable follow-up time of 2-3 years | Clavien-Dindo grade 2 complications (requiring pharmacological treatment) |
| Access-related complications per patient-year (2) | Variable follow-up time of 2-3 years | Access-related serious adverse events (Clavien-Dindo grade 4 and 5 complications, and vascular access thrombosis) |
| All-cause mortality | Variable follow-up time of 2-3 years | All-cause mortality |
| Access-related health care costs (1) | Every 3 months for 2-3 years from randomization (variable follow-up time) | Medical Consumption Questionnaire |
| Access-related health care costs (2) | Every 3 months for 2-3 years from randomization (variable follow-up time) | Productivity Cost Questionnaire |
| Patient-reported outcome measures (1) | Every 3 months for 2-3 years from randomization (variable follow-up time) | SF-VAQ (Short-Form Vascular Access Questionnaire) |
| Patient-reported outcome measures (2) | Every 3 months for 2-3 years from randomization (variable follow-up time) | EQ-5D-5L |
| Quality of the surveillance program (1) | Variable follow-up time of 2-3 years | Repeatability and reproducibility of vascular access flow volume measurements |
| Quality of the surveillance program (2) | Variable follow-up time of 2-3 years | 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 |
| Quality of the surveillance program (3) | Variable follow-up time of 2-3 years | 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) |
| Quality of the surveillance program (4) | Variable follow-up time of 2-3 years | Vascular access patency after balloon angioplasty |
| Primary patency | Variable follow-up time of 2-3 years | This outcome measure will be registered for explanatory analyses |
| Assisted primary patency | Variable follow-up time of 2-3 years | This outcome measure will be registered for explanatory analyses |
| Secondary patency | Variable follow-up time of 2-3 years | This outcome measure will be registered for explanatory analyses |
| The number of hemodialysis sessions with cannulation difficulties | Variable follow-up time of 2-3 years | This outcome measure will be registered for explanatory analyses |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORMaarten G Snoeijs, MD PhD
Maastricht University Medical Center
Outcome results
None listed