Graft-first Versus Fistula-first in Older Patients With End-stage Kidney Disease

Study Overview
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Brief Summary
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Many older adults require hemodialysis for advanced chronic kidney disease, but it is not clear which permanent vascular access method (fistula or graft) is best with respect to access effectiveness and patient satisfaction. In this pilot study, the study team will test the hypothesis that older adults undergoing graft access placement will more effectively transition from catheter-based to arteriovenous access-based hemodialysis; have fewer following vascular access procedures; have better upper extremity function; have better self-sufficiency with daily activities; and better health-related quality of life compared to those who undergo arteriovenous fistula access placement. The study will establish feasibility of randomizing older adults to the two types of arteriovenous access surgeries; evaluate relationships between measurements of pre-operative physical function and vascular access development; compare vascular access outcomes between the two groups; and gather longitudinal assessments of upper extremity muscle strength, performance of activities of daily living, and patients' reports of satisfaction with their vascular access and quality of life.

Detailed Description
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Each year, more than 600,000 people in the United States receive life-saving hemodialysis (HD) treatments for end-stage kidney disease (ESKD), a third of whom are older adults.Timely placement of an arteriovenous (AV) vascular access (native AV fistula [AVF] or prosthetic AV graft [AVG]) is necessary to avoid (or limit) the use of tunneled central venous catheters (TCVC) for HD. 'Fistula First Catheter Last' national guidelines require placement of AVF as the AV access of first choice in all patients to achieve better patient survival. However, the benefits of AVF over AVG are least certain in older adults, as age-related biological changes independently modulate patient outcomes. Nationally representative cohort studies of older adults with incident ESKD have shown similar patient survival between those whose first AV access placed or used was a fistula or a graft.Compared with grafts, fistulas fail more often and necessitate longer times and more subsequent procedures to aid development, exposing older patients to time-consuming procedures that may negatively affect upper extremity strength and erode their quality of life. The contribution of pre-operative physical function to AV access outcomes and the impact of AV access placement on upper extremity strength and self-sufficiency have not been evaluated. This pilot trial will involve older adults with pre-dialysis advanced chronic kidney disease (CKD) or incident ESKD using a TCVC for HD who had no prior AV access surgery and have upper extremity vasculature suitable for either fistula or graft placement. Participants will be randomized to receive an upper extremity AVF-first or AVG-first access for HD. The primary objective of this pilot trial is to prospectively evaluate patient and vascular access outcomes in a randomized intervention and in a patient population in whom fistula-first guidelines have been applied despite the lack of proven benefit and at the detriment of more access failures and procedures.

Official Title
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A Randomized Pilot Study Comparing Graft-first to Fistula-first Strategies in Older Patients With Incident End-stage Kidney Disease

Conditions
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Kidney Diseases

Intervention / Treatment
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* Procedure: Upper arm arteriovenous graft surgery
* Procedure: Upper arm arteriovenous fistula surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years End-stage kidney disease (ESKD) on chronic hemodialysis (HD) Tunneled central venous catheter (TCVC) is the sole vascular access used for HD Advanced chronic kidney disease (CKD) expected to require HD initiation within 90 days of screening and deemed medically necessary by the treating nephrologist to proceed with arteriovenous (AV) access placement in preparation for HD initiation Did not undergo AV access placement in the past Medically eligible to receive AV fistula (AVF) or AV graft (AVG) placement as deemed by the treating nephrologist Surgically eligible to receive either an AVF or an AVG as deemed by the vascular surgeon HD is the intended long-term modality of treatment for ESKD Planning to remain within Wake Forest provided health care for at least 12 months Exclusion Criteria: Presence of an AVF or AVG Previous attempt(s) for AV vascular access placement Native vasculature not suitable for placement of AV access Imminent transplant planned (within 6 months) Anticipated life expectancy <9 months

Ages Eligible for Study
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Minimum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upper extremity arteriovenous graft (AVG) - first<br>Participants randomized to receive an AVG will undergo surgery to have an AVG placed. | Procedure: Upper arm arteriovenous graft surgery<br>* Creation of arteriovenous graft vascular access for hemodialysis<br>|
| Active Comparator: Upper extremity arteriovenous fistula (AVF) - first<br>Participants randomized to receive an AVF will undergo surgery to have an AVF created. | Procedure: Upper arm arteriovenous fistula surgery<br>* Creation of arteriovenous fistula vascular access for hemodialysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility- Eligibility for Randomization | Proportion of screened participants deemed eligible for randomization. | 12 months | 
| Feasibility- Consent to Randomization | Proportion of eligible participants who consent to randomization. | 12 months | 
| Feasibility- AV Graft or Fistula Placement | Proportion of participants who undergo AV graft or fistula placement within 90 days of randomization. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Extremity Strength | The grip-strength test will be performed twice on each hand for each assessment and the mean of the two results will be used for statistical analyses; a cut-off point <16 kg in women and <26 kg in men will define muscle weakness. Changes in grip strength will be compared between the two access interventions. Assessed with upper arm grip-strength test in each arm using a hand-held dynamometer. | 3 and 6 months | 
| Patient Satisfaction With Vascular Access | Vascular access questionnaire will be used to assess differences in patient satisfaction with vascular access between the two access interventions using the short-form vascular access questionnaire (SF-VAQ). Mean scores obtained on SF-VAQ will be compared. SF-VAQ score range 4 -20 with higher scores indicating more satisfaction with the vascular access. | 3 and 6 months | 
| Performance on Activities of Daily Living (ADLs) | The level of independence will be evaluated using ADLs. ADL score range 0-30, with higher scores denoting more dependence on other people to perform the usual daily activities. | Baseline and 6 months | 
| Performance on Activities of Instrumental Daily Living ADLs (IADLs) | The level of independence will be evaluated using IADLs instruments. ADL score range 0-31, with higher scores denoting more dependence on other people. | Baseline, 3 and 6 months | 
| Depression | Depression scores assessed with the patient health questionnaire (PHQ-9) will be compared between the two vascular access arms. PHQ-9 score range 0-27. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. | 3 and 6 months | 
| Health-related Quality of Life (HRQoL) - Mental Health (MCS-12) Scores | The impact of the two types of vascular access on HRQoL will be assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.3. which consists of a generic core (Short Form-36 [SF-36]) and an 11-item kidney disease-specific scale. Score range 0 to 100, with higher scores reflecting better quality of life. | Baseline, Month 3, and Month 6 | 
| Health-related Quality of Life (HRQoL) - Physical Health (PCS-12) Scores | The impact of the two types of vascular access on HRQoL will be assessed using the Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.3. which consists of a generic core (Short Form-36 [SF-36]) and an 11-item kidney disease-specific scale. Score range 0 to 100, with higher scores reflecting better quality of life. | 3 and 6 months | 
| Physical Activity Level | The Rapid Assessment of Physical Activity (RAPA) instrument will be used to assess habitual physical activity. RAPA test score ≤ 3 corresponded to a sedentary lifestyle or a very light activity level; values ≥4 indicated a moderate to vigorous active lifestyle. | 3 and 6 months | 
| Physical Activity Level 4-meter Gait | The 4MGS test is a simple screening test and a useful predictor of worsening daily activity in patients with chronic respiratory diseases. | Baseline, month 3 and 6 | 
| Number of Subjects With No Pain at the AV Access Site | This will be determined by using the Verbal Descriptor Scale (VDS). The Verbal Descriptor Scale (VDS) is comprised of a series of descriptive phrases that refer to different levels of pain severity or intensity. Patients select the phrase that best describes their current pain - The verbal descriptor scale asks the patient to describe her or his pain using the following descriptors: no pain, mild pain, moderate pain, severe pain, or pain as bad as it could be. | Baseline, 3 and 6 months | 
| Number of Subjects With Mild Pain at the AV Access Site | This will be determined by using the Verbal Descriptor Scale (VDS). The Verbal Descriptor Scale (VDS) is comprised of a series of descriptive phrases that refer to different levels of pain severity or intensity. Patients select the phrase that best describes their current pain - The verbal descriptor scale asks the patient to describe her or his pain using the following descriptors: no pain, mild pain, moderate pain, severe pain, or pain as bad as it could be. | Baseline, Month 3 and Month 6 | 
| Number of Subject With Moderate Pain at the AV Access Site | This will be determined by using the Verbal Descriptor Scale (VDS). The Verbal Descriptor Scale (VDS) is comprised of a series of descriptive phrases that refer to different levels of pain severity or intensity. Patients select the phrase that best describes their current pain - The verbal descriptor scale asks the patient to describe her or his pain using the following descriptors: no pain, mild pain, moderate pain, severe pain, or pain as bad as it could be. | Baseline, Month 3 and Month 6 | 
| Number of Subjects With Severe Pain at the AV Access Site | This will be determined by using the Verbal Descriptor Scale (VDS). The Verbal Descriptor Scale (VDS) is comprised of a series of descriptive phrases that refer to different levels of pain severity or intensity. Patients select the phrase that best describes their current pain - The verbal descriptor scale asks the patient to describe her or his pain using the following descriptors: no pain, mild pain, moderate pain, severe pain, or pain as bad as it could be. | Baseline, Month 3 and Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft, fistula, hemodialysis, Vascular access