Recommended Clinical Trial End Points for Dialysis Catheters

Abstract

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 () complete a single dialysis session without triggering recurrent pressure alarms or () 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.

Evidence‐Based Strategies and Recommendations for Preservation of Central Venous Access in Children

“…The port septum should be distant from contaminated sites. Chronic hemodialysis catheters are ideally tunneled, cuffed devices that should deliver adequate dialysis blood flow to achieve target dose (Kt/V at least 1.2) while arterial and venous pressures remain within acceptable parameters …”

“…Chronic hemodialysis catheters are ideally tunneled, cuffed devices that should deliver adequate dialysis blood flow to achieve target dose (Kt/V at least 1.2) while arterial and venous pressures remain within acceptable parameters. 89 Antibiotic-impregnated catheters have shown significant reduction in catheter-related infections in high-risk children 90 and have demonstrated superiority to conventional and heparin-bonded catheters in a large pediatric RCT 91 without increasing resistance to bacterial pathogens. 92 They may be especially valuable for children in the intensive care unit 91 and those with intestinal overgrowth, 93 those with active infection at the time of insertion, 4,90 immunocompromised patients, those with a history of multiple catheter-related infections, or those with deep venous obstruction of VANGUARD Class II or higher either above or below the diaphragm (Appendix 4).…”

Strategies to improve vascular access outcomes in haemodialysis patients

“…In March 2018, the Kidney Health Initiative (KHI), a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration (FDA), published a four-paper series on clinical trial endpoints for HD vascular access 126,[131][132][133] . The KHI Clinical Trial Endpoints for Dialysis Vascular Access project aimed to improve the consistency of trial endpoints and outcome definitions related to HD vascular access.…”

“…The ability to assess the comparative effects of interventions on vascular access complications has been limited by inconsistent outcome reporting 28,64,68,186 . The need to standardise reporting of critically important outcomes has been widely advocated 127,[131][132][133] and there is a growing number of initiatives to establish core outcome sets, defined as an agreed minimum set of standardised outcomes that should be measured and reported in all trials for a specific clinical area 136,211,229,246 .…”

“…To improve the relevance and consistency of vascular access outcome measures used in clinical trials and day-to-day clinical practice, we recommend implementation of trial endpoints tailored to the different types of vascular access and time points of their life cycle. These were recently published by the Dialysis VascularAccess group of the American Society of Nephrology KHI126,[131][132][133] . Complementing the KHI, the international SONG Initiative has established a core outcome set for HD that includes vascular access as one of four core outcome domains based on the shared priorities of patients and health professionals9,11 .…”