Evaluation of Blood Volume Analysis- Guided Management of Decompensated Heart Failure

Diuretic therapy is first-line treatment for acute decompensated heart failure. However, accurate assessment and management of patient blood volume is challenged by the limitations of physical exam and surrogate markers for blood volume. The study primary objective is to determine if goal-directed care as quantified by direct Blood Volume Analysis (Daxor BVA-100™) in addition to usual care results in more appropriate treatment and consistent achievement of euvolemia.

Study Overview

• Status: Completed
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Diagnostic test: BVA-100

Detailed Description

Over 6 million Americans suffer from heart failure, one of the most prevalent and deadly diseases in the United States. High rates of rehospitalization and mortality and treatment costs have persisted for decades despite advances in care. Clinical guidelines recommend assessment of blood volume and clinical management to euvolemia or normal blood volume, but standard methods of diagnosing blood volume status have been shown to be unreliable. Blood Volume Analysis (Daxor BVA-100) is based on the gold standard indicator dilution technique. BVA has been used to quantify otherwise undiagnosed blood volume derangements and guide treatment in heart failure and other indications. Also, retrospective analyses have shown that care of heart failure patients guided by BVA is associated with improved rates of rehospitalization and mortality.

The proposed study is a prospective, two-center, parallel design, interventional, single-blinded pilot study of the potential for BVA to positively impact the treatment decisions of ADHF clinicians.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jonathan Feldschuh; Phone Number: 9176091893; Email: jafeldschuh@daxor.com

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age > 18 years. In accordance with the Inclusion Across the Lifespan policy, Children will be excluded from the proposed study. ADHF is a condition that rarely affects children and Daxor's BVA-100 lack the reference norms for pediatric use.
2. Admission to the hospital with a primary diagnosis of ADHF.
3. Able and willing to provide informed written consent.

Exclusion Criteria:

1. Evidence of acute coronary syndrome or myocardial infarction during qualifying ADHF hospitalization.
2. Evidence of hypertensive crisis or acute valvular regurgitation.

3. The following has occurred within the last 3 months or is planned within the following 3 months:

   1. Revascularization procedure.
   2. Placement on cardiac transplantation list.
   3. Other major cardiac surgery or other surgery.
4. Planned intermittent or continuous intravenous positive inotropic therapy.
5. Severe chronic kidney disease (eGFR<15 ml/min).
6. Psycho-social factors that interfere with ability to adhere to study procedures (severe dementia, active substance abuse, poorly controlled psychiatric illnesses).
7. Pregnant women or nursing mothers.
8. Women of childbearing potential not using adequate birth control methods.
9. Known hypersensitivity to iodine or eggs.
10. Participation in another heart failure investigational treatment protocol currently or <30 days prior to enrollment.
11. Evidence of active bleeding or active hemolysis.
12. Hemoglobin measured below 7 g/dl or hematocrit measured below 21%.
13. Patient has received a heart transplant and/or currently treated with mechanical circulatory support.
14. Patients implanted with invasive hemodynamic monitors (i.e. CardioMEMS).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard care group; Blood Volume Analysis will be performed at admission, during inpatient stay if warranted, and prior to hospital discharge. Treating physicians will be blinded to the results and will choose between a low-moderate and high diuretic dose based on usual care clinical assessment of volume status.	Diagnostic test: BVA-100; The BVA-100 is a medical device that calculates human blood volume using the method of tracer dilution. The device utilizes a tracer of human serum albumin tagged with iodine-131 to measure injected intravascularly and a series of timed blood draws. The amount of tracer in each blood draw is used to calculate the unknown blood volume. Data inputs come from the measured characteristics of subject blood samples (hematocrit and tracer concentration) and tracer calibration standards. The package also calculates the subject expected (or ideal) blood volume from physical parameters. Hyper- or hypovolemia, associated red blood cell volumes, and tracer transudation rate are reported, with statistics showing the quality of the results.
Experimental: BVA-guided treatment arm; Blood Volume Analysis will be performed at admission, during inpatient stay if warranted, and prior to hospital discharge. Treating physicians will receive the results and will choose between a low-moderate and high diuretic dose based on measured volume status.	Diagnostic test: BVA-100; The BVA-100 is a medical device that calculates human blood volume using the method of tracer dilution. The device utilizes a tracer of human serum albumin tagged with iodine-131 to measure injected intravascularly and a series of timed blood draws. The amount of tracer in each blood draw is used to calculate the unknown blood volume. Data inputs come from the measured characteristics of subject blood samples (hematocrit and tracer concentration) and tracer calibration standards. The package also calculates the subject expected (or ideal) blood volume from physical parameters. Hyper- or hypovolemia, associated red blood cell volumes, and tracer transudation rate are reported, with statistics showing the quality of the results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative assessment of progress to euvolemic target for both subjects and controls	Accurately quantify levels and changes to blood volume and red blood cell volume in ADHF inpatients during inpatient stay, and use this data to guide diuretic therapy in the treatment arm.	Approximately 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative assessment of event-based outcome metrics	30-day readmission and mortality outcomes will be quantified for both cohorts.	30 days post discharge
Quantitative assessment of continuous outcome metrics: weight	Measure and compare changes to body weight in kilogram	Approximately 2 weeks
Quantitative assessment of continuous outcome metrics: net fluid balance	Measure and compare changes to net fluid balance in mL	Approximately 2 weeks
Quantitative assessment of continuous outcome metrics: natriuretic peptide	Measure and compare changes to natriuretic peptide in pg/mL	Approximately 2 weeks

Collaborators and Investigators

• Sponsor: Daxor Corporation
• Collaborators: Minneapolis Veterans Affairs Medical Center; VA Boston Healthcare System
• Investigators: Principal Investigator: Jacob Joseph, Boston VA Healthcare System; Principal Investigator: Bradley Bart, Minneapolis Veterans Affairs Medical Center; Principal Investigator: Orly Vardeny, Minneapolis Veterans Affairs Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Blood Volume
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: BVA for inpatient HF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will primarily be captured from Clinical Report Forms and de-identified data will be transferred from the clinical sites to Daxor for analysis. All PHI used to abstract data will remain on the VA Health System servers and will not be transported outside for any research purpose. In accordance with VA policy, incident reporting of theft, loss of data, loss of storage media, unauthorized access to sensitive data or storage media and non-compliance with security controls will be reported promptly to the study PI, Privacy Officer and Information Security Officer.
• IPD Sharing Time Frame: Data will become available as collected throughout the study, and will be available for 18months prior to the completion of the study, for analysis.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No