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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases
• Intervention / Treatment: Procedure: Upper arm arteriovenous graft surgery; Procedure: Upper arm arteriovenous fistula surgery

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Upper extremity arteriovenous graft (AVG) - first; Participants randomized to receive an AVG will undergo surgery to have an AVG placed.	Procedure: Upper arm arteriovenous graft surgery; Creation of arteriovenous graft vascular access for hemodialysis
ACTIVE_COMPARATOR: Upper extremity arteriovenous fistula (AVF) - first; Participants randomized to receive an AVF will undergo surgery to have an AVF created.	Procedure: Upper arm arteriovenous fistula surgery; Creation of arteriovenous fistula vascular access for hemodialysis

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AV Access Primary Failure	Rate of AV access primary failure between the two AV access strategies. Primary access failure is defined as permanent failure of the fistula or graft before hemodialysis suitability. This will include inadequate maturation, thrombosis, failure of first and subsequent cannulations, and/or other complications leading to nonfunctional fistula or graft.	6 months
AV Access Infection	Incidence rate of AV access infection between the two AV access strategies. This will include fistula or graft cellulitis, abscess, and/or bacteremia due to AV access infection.	12 months
AV Access Successful Cannulation	Will compare the proportion of patients with successful AV access cannulation between the two AV access strategies. Successful cannulation is defined by the use of the AV access as the primary vascular access for hemodialysis (the fistula or graft access has been cannulated with two 16- or 15-gauge needles for ≥3 consecutive dialysis sessions and the dialysis central venous catheter was removed).	6 months
AV Access Secondary Failure	Rate of AV access secondary failure between the two AV access strategies. Secondary access failure is defined by permanent AV access failure after the fistula or graft met dialysis suitability criteria with subsequent abandonment.	12 months
AV Access Procedures - Number of Surgical Re-intervention on Index AV Access Procedures	Number of AV access procedures per 100 patient-days between the two AV access strategies. This will include angioplasty, thrombectomy, stent placement, repeat surgery, and/or surgical superficialization.	12 months
AV Access Procedures - Number of Endovascular Interventions on Index AV Procedures Access	Number of AV access procedures per 100 patient-days between the two AV access strategies. This will include angioplasty, thrombectomy, stent placement, repeat surgery, and/or surgical superficialization.	12 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Lok CE, Allon M, Moist L, Oliver MJ, Shah H, Zimmerman D. Risk equation determining unsuccessful cannulation events and failure to maturation in arteriovenous fistulas (REDUCE FTM I). J Am Soc Nephrol. 2006 Nov;17(11):3204-12. doi: 10.1681/ASN.2006030190. Epub 2006 Sep 20.
• Vascular Access 2006 Work Group. Clinical practice guidelines for vascular access. Am J Kidney Dis. 2006 Jul;48 Suppl 1:S176-247. doi: 10.1053/j.ajkd.2006.04.029. No abstract available.
• Murea M, Burkart J. Finding the right hemodialysis vascular access in the elderly: a patient-centered approach. J Vasc Access. 2016 Sep 21;17(5):386-391. doi: 10.5301/jva.5000590. Epub 2016 Aug 1.
• Yuo TH, Chaer RA, Dillavou ED, Leers SA, Makaroun MS. Patients started on hemodialysis with tunneled dialysis catheter have similar survival after arteriovenous fistula and arteriovenous graft creation. J Vasc Surg. 2015 Dec;62(6):1590-7.e2. doi: 10.1016/j.jvs.2015.07.076. Epub 2015 Sep 12.
• Peterson WJ, Barker J, Allon M. Disparities in fistula maturation persist despite preoperative vascular mapping. Clin J Am Soc Nephrol. 2008 Mar;3(2):437-41. doi: 10.2215/CJN.03480807. Epub 2008 Jan 30.
• Woo K, Goldman DP, Romley JA. Early Failure of Dialysis Access among the Elderly in the Era of Fistula First. Clin J Am Soc Nephrol. 2015 Oct 7;10(10):1791-8. doi: 10.2215/CJN.09040914. Epub 2015 Aug 7.
• DeSilva RN, Patibandla BK, Vin Y, Narra A, Chawla V, Brown RS, Goldfarb-Rumyantzev AS. Fistula first is not always the best strategy for the elderly. J Am Soc Nephrol. 2013 Jul;24(8):1297-304. doi: 10.1681/ASN.2012060632. Epub 2013 Jun 27.
• Richardson AI 2nd, Leake A, Schmieder GC, Biuckians A, Stokes GK, Panneton JM, Glickman MH. Should fistulas really be first in the elderly patient? J Vasc Access. 2009 Jul-Sep;10(3):199-202. doi: 10.1177/112972980901000311.
• Robinson T, Geary RL, Davis RP, Hurie JB, Williams TK, Velazquez-Ramirez G, Moossavi S, Chen H, Murea M. Arteriovenous Fistula Versus Graft Access Strategy in Older Adults Receiving Hemodialysis: A Pilot Randomized Trial. Kidney Med. 2021 Feb 10;3(2):248-256.e1. doi: 10.1016/j.xkme.2020.11.016. eCollection 2021 Mar-Apr.
• Murea M, Geary RL, Houston DK, Edwards MS, Robinson TW, Davis RP, Hurie JB, Williams TK, Velazquez-Ramirez G, Bagwell B, Tuttle AB, Moossavi S, Rocco MV, Freedman BI, Williamson JD, Chen H, Divers J. A randomized pilot study to evaluate graft versus fistula vascular access strategy in older patients with advanced kidney disease: results of a feasibility study. Pilot Feasibility Stud. 2020 Jun 17;6:86. doi: 10.1186/s40814-020-00619-9. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 4, 2018
• Primary Completion (ACTUAL): February 22, 2021
• Study Completion (ACTUAL): February 22, 2021

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (ACTUAL): June 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: hemodialysis; graft; fistula; Vascular access
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Pathological Conditions, Anatomical; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Fistula
• Other Study ID Numbers: IRB00050577; R03AG060178-02 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results obtained in the pilot trial, deidentified.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following the first article publication that stems from this pilot trial.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal and whose proposed use of data has been approved by an independent review party identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No