Blood Pressure Slopes and Ultrafiltration in Hemodialysis Patients

Using Intradialytic Blood Pressure Slopes to Guide Ultrafiltration in Hemodialysis Patients

Kidney failure has been recognized as one of the most costly chronic conditions among United States Veterans. Approximately 13,000 Veterans develop kidney failure each year, and most require hemodialysis initiation. Hemodialysis patients suffer significantly increased risk of death and hospitalizations, and excessive body fluid is a major cause of this. While empiric aggressive fluid removal during dialysis is one approach to limit fluid overload, this can cause dangerous decreases in blood pressure during dialysis that independently contribute to the high death rate. In this study, I aim to test a new strategy that prescribes fluid removal based on a patient's recent blood pressure patterns during dialysis. This clinical trial will compare my strategy to standard care and assess the outcomes of overall blood pressure change between dialysis treatments in addition to the number of times the blood pressure becomes dangerously low during dialysis. Another aim is to determine how differences in the structure and function of the heart influence blood pressure during dialysis.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; End Stage Renal Disease; Intradialytic Hypotension; Extracellular Volume Overload
• Intervention / Treatment: Other: IBPS-Guided Ultrafiltration

Detailed Description

United States Veterans have disproportionately higher risk for end stage renal disease (ESRD) compared to the general population. Veterans with ESRD on maintenance hemodialysis (HD) suffer from alarmingly high mortality rates and hospitalizations mainly related to cardiovascular disease. Extracellular volume (ECV) excess is a primary contributing factor to cardiovascular disease and the heightened mortality rate in HD patients. Extracellular volume excess remains difficult to identify in clinical practice, and the standard approach to fluid management in the clinical setting involves arbitrary trial and error attempts to remove fluid without invoking hemodynamic instability such as intradialytic hypotension. Bioimpedance spectroscopy (BIS) is a useful research tool for assessing ECV; however, it is not feasible in routine practice, and there is little data on how its use affects intermediate and hard clinical outcomes. There is an unmet need for an approach to guide ultrafiltration in clinical practice that addresses both reduction of ECV and other mortality outcomes as well as minimization of intradialytic hypotension. The long-term goal of this study is to develop a more precise, patient-specific fluid management approach to be tested in a large clinical trial aimed at reducing mortality in Veterans on HD. The overall objective of this project is to utilize the investigators' novel, patient-specific ultrafiltration algorithm as an intervention in a clinical trial using mortality risk factors as the primary outcomes. The central hypothesis is that prescribing ultrafiltration prospectively based on an individual patient's intradialytic blood pressure slopes (IBPS) from recent treatments is superior to standard care at reducing ambulatory blood pressure and ECV without increasing risk for intradialytic hypotension. Aim 1 will use an un-blinded, controlled randomized clinical trial to demonstrate the effects of an IBPS-based ultrafiltration prescription compared to standard clinical practice. Each month, updated ultrafiltration prescriptions for the IBPS group will be determined based on the most recent treatment data. The primary outcome will be change in mean systolic 44-hour ambulatory blood pressure after 4 months. Other outcomes will include 1) change in post-HD ECV/body weight using multifrequency bioimpedance spectroscopy, 2) change in post-HD total peripheral resistance index using a non-invasive cardiac output monitor, and 3) between-group comparison of the frequency of intradialytic hypotension and intradialytic symptoms. Aim 2 will involve a cross sectional analysis of baseline data of subjects from Aim 1 in addition to consecutive enrollment of additional hypertensive HD patients. In addition to Aim 1 measurements, subjects will undergo transthoracic echocardiograms on a non-HD day to obtain measurements of left ventricular ejection fraction as a metric of systolic function, mitral inflow and mitral annulus velocities as a metric of diastolic function, and left ventricular mass index. Mixed linear models will be used to determine how these metrics independently influence the association between ECV/body weight and IBPS. The strength of the association between IBPS and ECV/body weight will then be determined within each tertile of the distributions of systolic and diastolic dysfunction. Finally, there will be an assessment of how the echocardiogram based metrics influence the likelihood of intradialytic hypotension with prospective follow up while controlling for ECV/body weight. If successful, this study will provide nephrologists with an easily-implemented, individualized approach to fluid management in Veterans on HD that safely reduces ECV excess and related mortality risk factors. Because no approach currently exits, this could immediately change clinical practice of managing Veterans with ESRD. The long term impact will be the opportunity to utilize the data generated to design a large, multi-center trial directly evaluating this intervention's effect on mortality in Veterans with ESRD on HD. The observed reduction in blood pressure can be used to determine expected mortality, while the echocardiogram data can be used to determine phenotypes of patients that may need to be considered for inclusion/exclusion criteria.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter N Van Buren, MD; Phone Number: (214) 857-2214; Email: peter.vanburen@va.gov

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75216-7167
      • Recruiting
      • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
      • Contact: Peter N Van Buren, MD; Phone Number: (214) 857-2214; Email: peter.vanburen@va.gov
      • Principal Investigator: Peter Noel Van Buren, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hemodialysis patient
• Pre-dialysis systolic blood pressure greater than 140 mmHg averaged over 2 weeks OR post-dialysis systolic blood pressure greater than 130 mmHg averaged over 2 weeks

Exclusion Criteria:

• HemoDialysis Vintage Less than 2 months
• Pregnancy
• Mean systolic blood pressure nadir <95 mmHg in 2 weeks screening
• Mean pre- or post-dialysis systolic blood pressure >180 mmHg
• Mean pre to post-HD decrease in blood pressure >60 mmHg
• Routine intradialytic clonidine use
• Routine intradialytic midodrine use
• Documented antihypertensive medication non-adherence
• Mean ultrafiltration rate >13 mL/kg/hr during 2 week screening
• For bioimpedance measurements only: amputation of a major extremity, presence of cardiac defibrillator or pacemaker, presence of a metallic implant (prosthetic joint)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Participants in the control group will have their blood pressure, fluid status, as well as all other aspects of clinical care managed in entirety by their treating nephrologists.
Experimental: IBPS (Intradialytic Blood Pressure Slope) Arm; IBPS participants will have their target weight adjusted each month by the study investigator based on recent assessment of intradialytic blood pressure slopes.	Other: IBPS-Guided Ultrafiltration; Each month, the study investigator will review the average intradialytic blood pressure slope from the prior two weeks. A prespecified algorithm will be used to prescribe additional fluid removal/weight reduction based on this slope.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory Systolic Blood Pressure	Will compare between-group difference in change in ambulatory systolic blood pressure from baseline to 4-month follow up	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular Volume	Will compare the between-group difference in change in post-dialysis extracellular water/body weight measured with multifrequency bioimpedance spectroscopy.	4 months
Total Peripheral Resistance Index	Will compare the between-group difference in change in post-dialysis total peripheral resistance index measured with a non-invasive cardiac output monitor.	4 months
Intradialytic Hypotension	The investigators will compare the between-group difference in the occurrence of intradialytic systolic blood pressure nadir less than 90 and 95 mmHg.	4 months
Association Between intradialytic blood pressure slope with systolic and diastolic dysfunction	The investigators will analyze the correlation between intradialytic blood pressure slopes with both ejection fraction and mitral inflow/mitral annuls velocities measured with transthoracic echocardiograms	3 days

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Peter Noel Van Buren, MD, VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2021
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Hypertension; Extracellular Volume; Intradialytic Hypotension; Bioimpedance Spectroscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Hypotension
• Other Study ID Numbers: NEPH-020-19S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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