Evaluation of Total Blood Volume Measurement During Dialysis on the Incidence of Intradialytic Hypotension

The Evaluation of the Influence of the Use of Total Blood Volume Measurement During Dialysis on the Incidence of Intradialytic Hypotension Associated Events

Establishing the euvolemic state in hemodialysis patients -the so called "dry weight"- is an important clinical conundrum in every nephrologist's daily practice. Underestimation of dry weight (with excessive ultrafiltration) results in dialysis-induced hypotension. Currently used methods to establish dry weight, including clinical assessment, bio-impedance spectroscopy and online relative blood volume (RBV) measurements, all have their limitations. RBV measurement reflects changes in blood volume during dialysis without providing any information about the initial hydration status, or the initial absolute blood volume (ABV). Recently, researchers proposed a new method to calculate ABV, by using the principle of dilution-indicator with RBV measurement. In a small cohort study they identified a total blood volume threshold of 65 millilitres per kilogram dry weight predicting for intra-dialytic hypotension associated symptoms.

The goal of current clinical trial is to re-investigate the accuracy of the above-described method and to confirm the hypothesis of a critical threshold of 65 ml blood volume per kg dry weight in haemodialysis patients. Researchers will compare adjustment of dry weight based on the ABV measurement with standard care to see if dialysis-induced hypotension will be reduced.

Study Overview

• Status: Completed
• Conditions: Hemodialysis Complication; Hypotension During Dialysis; Diagnostic Tests
• Intervention / Treatment: Diagnostic test: adjustment of dry weight based on absolute blood volume measurement

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Den Haag, Netherlands, 2545 AA
    • Hagaziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• hemodialysis patients of three dialysis locations of the Haga Hospital (Zoetermeer, The Hague Leyweg and The Hague Sportlaan).
• Maintenance hemodialysis, with initiation of treatment predates inclusion in the study by at least 3 months.
• Hemodialysis scheme three times weekly for four hours
• Age above 18 years.

Exclusion Criteria:

• Clinically relevant fistula dysfunction resulting in single poold Kt/V <1,2
• Severe volume overload with a contraindication to bolus fluid infusion during dialysis according to the treating physician.
• Severe cardiac dysfunction responsible for >1x intradialytic hypotension associated adverse event /week according to treating physician
• Severe liver failure with or without presence of ascites
• More than three hemodialysis sessions per week
• Single needle treatment
• Central venous access
• Residual diuresis > 500 ml/ 24h
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm: adjustment of dry weight based on absolute blood volume measurement; Dry weight will be adjusted at the start of the intervention period in all subjects in the intervention group with a normalized blood volume below 65 ml/kg, regardless the occurrence of intradialytic hypotension associated adverse events during the baseline period. Dry weight will be adjusted once with 0,5kg.	Diagnostic test: adjustment of dry weight based on absolute blood volume measurement; adjustment of dry weight based on absolute blood volume measurement
No Intervention: Control arm: standard care; standard care provided by the clinician, no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference in the incidence of intradialytic hypotension-associated adverse events between the intervention and control group	The incidence of intradialytic hypotension-associated adverse events (IHAAE) will be compared at baseline and after intervention, using questionnaires. Participants will undergo a 4-week run-in period to assess baseline incidence. The incidence of IHAAE will be calculated by dividing the number of dialysis treatments with one or more symptoms attributable to IHAAE as a percentage of the total number of dialysis treatments with a completed questionnaire. After randomization and the intervention, the occurence of IHAAE will be measured in both arms for another four weeks. Differences in incidence of IHAAE between groups will be analyzed using ANCOVA, adjusting for baseline IHAAE, pre-dialysis blood pressure and the use of anti-hypertensive agents. IHAAE is defined as a systolic blood pressure < 90 mmHg Either symptomatic or asymptomatic, or solely symptoms associated to (impeding) hypotension like dizziness, lightheadedness, sweating, cramps or visuel disturbances.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline incidence of intradialytic hypotension associated adverse events (IHAAE) in the entire study population.	Eligible participants will undergo a 4-week run-in period to assess baseline incidence of IHAAE, using questionnaires. The incidence of IHAAE will be calculated by dividing the number of dialysis treatments with one or more symptoms attributable to IHAAE as a percentage of by the total number of dialysis treatments with a completed questionnaire.	baseline
Reproducibility of absolute blood volume measurement	Absolute blood volume (ABV) will be measured twice in the entire study population, at the start of two mid-weekly hemodialysis treatments. We will investigate the correlation between these two test results, using Bland Altman Analysis.	2 weeks
Correlation of absolute blood volume measurement with other diagnostic tests to determine blood volume	We will calculate antropomorphic blood volume in the whole study population, using the Nadler's formula. We will randomly select 10 participants for ABV measurement with the reference method.This technique is based on the isotope-dilution principal using I-251 radiolabeled human serum albumin. Adverse events due to the infusion of radioactive labelled albumin are very rare (0.01-0.1%, <0.01 % anaphylactic reactions). For a 70kg-patient the dose will be 0,02 millisievert. This falls within risk category I according to the International Commission on Radiological Protection (ICRP). This is the lowest risk category with a statistical probability of less than five in a million to develop radiation induced cancer. Annual background radiation level in the Netherlands is about 2,5 mSv. We will correlate the results of these diagnostic tests to our ABV measurement, using Bland Altman analysis.	2 weeks
Sensitivity, specificity	We will use the values of absolute volume measurement and incidence of IHAAE to calculate sensitivity, specificity of the previously defined critical threshold of normalized blood volume of 65 ml/kg for the occurrence of IHAAE.	10 weeks
positive predictive value, negative predictive value	We will use the values of absolute volume measurement and incidence of IHAAE to calculate positive and negative predictive value of the previously defined critical threshold of normalized blood volume of 65 ml/kg for the occurrence of IHAAE.	10 weeks

Collaborators and Investigators

• Sponsor: HagaZiekenhuis
• Investigators: Principal Investigator: Louis Jean Vleming, dr, Hagaziekenhuis

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hemodialysis; Intradialytic hypotension; Intradialytic morbid events
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension
• Other Study ID Numbers: NL71892.058.19

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