Flow Dysfunction of Hemodialysis Vascular Access (FLOW)

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

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.

Study Overview

• Status: Completed
• Conditions: Hemodialysis Access Failure; Dialysis Access Malfunction; Vascular Access Malfunction; Hemodialysis Fistula Thrombosis
• Intervention / Treatment: Diagnostic test: Vascular access monitoring; Diagnostic test: Vascular access blood flow measurement

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.

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • OLVG
  • Amsterdam, Netherlands
    • Diapriva - Dialyse Centrum Amsterdam
  • Deventer, Netherlands
    • Deventer Ziekenhuis
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Haarlem, Netherlands
    • Spaarne Gasthuis
  • Heerlen, Netherlands
    • Zuyderland Medisch Centrum
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum
  • Maastricht, Netherlands
    • Maastricht UMC+
  • Roosendaal, Netherlands
    • Bravis ziekenhuis
  • Rotterdam, Netherlands
    • Franciscus Gasthuis & Vlietland
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
  • Veldhoven, Netherlands
    • Maxima Medisch Centrum
  • Zwolle, Netherlands
    • Isala Klinieken

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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: 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.	Diagnostic test: Vascular 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.
Active Comparator: 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.	Diagnostic test: Vascular 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 test: Vascular 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Maarten G Snoeijs, MD PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Embolism and Thrombosis; Thrombosis; Fistula
• Other Study ID Numbers: NL75845.068.20; NL9165 (Registry Identifier: Netherlands Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The size of the data collection is unknown but includes physical examination forms, Transonic flow measurement curves, angiography videos, and intervention notes.

The following end products will be made available for further research and verification: data documentation; documentation of the research process, including documentation of all participants; audiovisual material / images; several versions of processed data; raw data.

• IPD Sharing Time Frame: The embargo period will be as long as required for publication of the research findings.
• IPD Sharing Access Criteria: Interested parties can submit a request for a data set.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No