Clinical Trial End Points for Hemodialysis Vascular Access: Background, Rationale, and Definitions.
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SUBMITTER: Shenoy S
PROVIDER: S-EPMC5967685 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Clinical Trial End Points for Hemodialysis Vascular Access: Background, Rationale, and Definitions.
Shenoy Surendra S Allon Michael M Beathard Gerald G Brouwer-Maier Deborah D Dember Laura M LM Glickman Mark M Lee Celeste C Litchfield Terry T Lok Charmaine C Huber Thomas T Roy-Chaudhury Prabir P Work Jack J West Melissa M Wasse Haimanot H
Clinical journal of the American Society of Nephrology : CJASN 20180227 3
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Project description:This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access' evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1-patent arteriovenous access, stage 2-physiologically mature arteriovenous access, and stage 3-clinically functional arteriovenous access. Once the requirements of a stage 3-clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.
| S-EPMC5967683 | biostudies-literature
Project description:BackgroundHemodialysis arteriovenous fistulas (AVFs) are the preferred vascular access for patients on hemodialysis. In the Hemodialysis Fistula Maturation Study, 44% of the patients achieved unassisted maturation of their fistula without needing an intervention. Venous neointimal hyperplasia (VNH) and subsequent venous stenosis are responsible for lack of maturation. There are no therapies that can prevent VNH/VS formation. The goal of this paper is to present the background, rationale, and trial design of an innovative phase 1/2 clinical study that is investigating the safety of autologous adipose-derived mesenchymal stem cells delivered locally to the adventitia of newly created upper extremity radiocephalic (RCF) or brachiocephalic fistula (BCF).MethodsThe rationale and preclinical studies used to obtain a physician-sponsored investigational new drug trial are discussed. The trial design and end points are discussed.ResultsThis is an ongoing trial that will complete this year.ConclusionThis is a phase 1/2 single-center, randomized trial that will investigate the safety and efficacy of autologous AMSCs in promoting maturation in new upper-extremity AVFs.Clinical Trial registration number: NCT02808208.
| S-EPMC8986037 | biostudies-literature
Project description: Not available
| S-EPMC7275157 | biostudies-literature
Project description:Central venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.
| S-EPMC5967684 | biostudies-literature
Project description:IntroductionCentral venous catheters (CVC) increase risks associated with hemodialysis (HD), but may be necessary until an arteriovenous fistula (AVF) or graft (AVG) is achieved. The impact of vascular imaging on achievement of working AVF and AVG has not been firmly established.MethodsRetrospective cohort of patients initiating HD with CVC in 2010-2011, classified by exposure to venography or Doppler vein mapping, and followed through December 31, 2012. Standard and time-dependent Cox models were used to determine hazard ratios (HRs) of death, working AVF, and any AVF or AVG. Logistic regression was used to assess the association of preoperative imaging with successful AVF or AVG among 18,883 individuals who had surgery. Models were adjusted for clinical and demographic factors.FindingsAmong 33,918 patients followed for a median of 404 days, 39.1% had imaging and 55.7% had surgery. Working AVF or AVG were achieved in 40.6%; 46.2% died. Compared to nonimaged patients, imaged patients were more likely to achieve working AVF (HR = 1.45 [95% confidence interval [CI] 1.36, 1.55], P < 0.001]), any AVF or AVG (HR = 1.63 [1.58, 1.69], P > 0.001), and less likely to die (HR = 0.88 [0.83-0.94], P < 0.001). Among patients who had surgery, the odds ratio for any successful AVF or AVG was 1.09 (1.02-1.16, P = 0.008).DiscussionFewer than half of patients who initiated HD with a CVC had vascular imaging. Imaged patients were more likely to have vascular surgery and had increased achievement of working AV fistulas and grafts. Outcomes of surgery were similar in patients who did and did not have imaging.
| S-EPMC5438785 | biostudies-literature
Project description:Background and objectivesThe optimal type of initial permanent access for hemodialysis among the elderly is controversial. Duration of central venous catheter dependence, patient comorbidities, and life expectancy are important considerations in whether to place an arteriovenous fistula or graft. We used an observational study design to compare clinical outcomes in elderly patients who initiated hemodialysis with a central venous catheter and subsequently had an arteriovenous fistula or graft placed.Design, setting, participants, & measurementsWe identified 9458 United States patients ages ≥67 years old who initiated hemodialysis from July 1, 2010 to June 30, 2011 with a central venous catheter and no secondary vascular access and then received an arteriovenous fistula (n=7433) or graft (n=2025) within 6 months. We evaluated key clinical outcomes during the 6 months after vascular access placement coincident with high rates of catheter use and used a matched propensity score analysis to examine patient survival.ResultsCentral venous catheter dependence was greater in every month during the 6-month period after arteriovenous fistula versus graft placement (P<0.001). However, rates of all-cause infection-related hospitalization (adjusted relative risk, 0.93; 95% confidence interval, 0.87 to 0.99; P=0.01) and bacteremia/septicemia-related hospitalization (adjusted relative risk, 0.90; 95% confidence interval, 0.82 to 0.98; P=0.02) were lower in the arteriovenous fistula versus graft group as was the adjusted risk of death (hazard ratio, 0.76; 95% confidence interval, 0.73 to 0.80; P<0.001).ConclusionsDespite extended central venous catheter dependence, elderly patients initiating hemodialysis with a central venous catheter who underwent arteriovenous fistula placement within 6 months had fewer hospitalizations due to infections and a lower likelihood of death than those receiving an arteriovenous graft.
| S-EPMC5672965 | biostudies-literature
Project description:BackgroundTreatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers.MethodsThis is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups.DiscussionIn the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making.Trial registrationThis study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).
| S-EPMC9960188 | biostudies-literature
Project description:Most arteriovenous grafts fail due to irreversible thrombosis, and most clotted grafts have an underlying stenotic lesion. These observations raise the plausible hypothesis that early detection of graft stenosis with preemptive angioplasty will reduce the likelihood of graft thrombosis. A number of noninvasive methods can be used to detect hemodynamically significant graft stenosis with a high positive predictive value. These tests include clinical monitoring, as well as surveillance by static dialysis venous pressures, flow monitoring, or duplex ultrasound. However, these surveillance tests have a much lower positive predictive value for graft thrombosis in the absence of preemptive angioplasty. In other words, none of the currently available surveillance tests can reliably distinguish between stenosed grafts destined to clot, and those that will remain patent without intervention. As a consequence, any program of graft surveillance necessarily results in a substantial proportion of unnecessary angioplasties. Moreover, a substantial proportion of grafts thrombose despite a normal antecedent surveillance test. Numerous observational studies have found an impressive reduction of graft thrombosis after implementation of a stenosis surveillance program. In contrast, 5 of 6 randomized clinical trials failed to show a reduction of graft thrombosis in patients undergoing graft surveillance, as compared with those receiving only clinical monitoring. The lack of benefit of surveillance is largely attributable to the rapid recurrence of stenosis after angioplasty. Thus, routine surveillance for graft stenosis, with preemptive angioplasty, cannot be recommended for reduction of graft thrombosis. Future research should be directed at pharmacologic interventions to prevent graft stenosis.
| S-EPMC4017945 | biostudies-literature
Project description:The arteriovenous fistula has been used for more than 50 years to provide vascular access for patients undergoing hemodialysis. More than 1.5 million patients worldwide have end stage renal disease and this population will continue to grow. The arteriovenous fistula is the preferred vascular access for patients, but its patency rate at 1 year is only 60%. The majority of arteriovenous fistulas fail because of intimal hyperplasia. In recent years, there have been many studies investigating the molecular mechanisms responsible for intimal hyperplasia and subsequent thrombosis. These studies have identified common pathways including inflammation, uremia, hypoxia, sheer stress, and increased thrombogenicity. These cellular mechanisms lead to increased proliferation, migration, and eventually stenosis. These pathways work synergistically through shared molecular messengers. In this review, we will examine the literature concerning the molecular basis of hemodialysis vascular access malfunction.
| S-EPMC4734360 | biostudies-literature
Project description:Frequent hemodialysis requires using the vascular access more often than with conventional hemodialysis, but whether this increases the risk for access-related complications is unknown. In two separate trials, we randomly assigned 245 patients to receive in-center daily hemodialysis (6 days per week) or conventional hemodialysis (3 days per week) and 87 patients to receive home nocturnal hemodialysis (6 nights per week) or conventional hemodialysis, for 12 months. The primary vascular access outcome was time to first access event (repair, loss, or access-related hospitalization). Secondary outcomes were time to all repairs and time to all losses. In the Daily Trial, 77 (31%) of 245 patients had a primary outcome event: 33 repairs and 15 losses in the daily group and 17 repairs, 11 losses, and 1 hospitalization in the conventional group. Overall, the risk for a first access event was 76% higher with daily hemodialysis than with conventional hemodialysis (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.11-2.79; P=0.017); among the 198 patients with an arteriovenous (AV) access at randomization, the risk was 90% higher with daily hemodialysis (HR, 1.90; 95% CI, 1.11-3.25; P=0.02). Daily hemodialysis patients had significantly more total AV access repairs than conventional hemodialysis patients (P=0.011), with 55% of all repairs involving thrombectomy or surgical revision. Losses of AV access did not differ between groups (P=0.58). We observed similar trends in the Nocturnal Trial, although the results were not statistically significant. In conclusion, frequent hemodialysis increases the risk of vascular access complications. The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance.
| S-EPMC3582201 | biostudies-literature