Clinical Validation Study for Optimization of Anemia MAnagement in Hemodialysis Patients With End Stage Kidney Disease Using the Dialysis Anemia TReatmenT Model (SMART)

This is a human subject research study conducted in patients undergoing dialysis treatment with darbepoetin alfa at Intermountain Utah Dialysis and Intermountain Medical Center Dialysis Services. The purpose is to test a dose recommendation algorithm that may reduce hemoglobin variability and drug cost.

Study Overview

• Status: Active, not recruiting
• Conditions: Dialysis
• Intervention / Treatment: Procedure: Standard of care; Procedure: Algorithm model-based Aranesp doses

Detailed Description

Hemoglobin cycling is an outcome of treating long-term dialysis patients for anemia using erythropoiesis-stimulating agents (ESAs), and represents a conundrum for practitioners. While patients with low hemoglobin levels suffer from anemia, high hemoglobin levels may lead to blood clots and subsequent health risks. The current protocol for ESA dosing often results in suboptimal dosing that leads to hemoglobin cycling, which can have a negative impact on patient survival. To this end, we have developed a personalized method for ESA dosing that controls anemia in dialysis patients that is similar to the commercial product sold by PhySoft. Our method, the Dialysis Anemia Treatment Model, uses a mathematical model for erythropoiesis that takes each patient's physiology into account, predicting the optimal dose of ESA for that patient to prevent hemoglobin cycling. The goal of this computer-aided approach is to reduce hemoglobin cycling and the amount of drug used by predicting optimal doses to keep the patient's hemoglobin within the desired range. This is a human subject research study to validate the model in the clinic and demonstrate that it is able to minimize hemoglobin cycling in patients and reduce the amount of ESA drug administered.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Haroldsen, MHA; Phone Number: (801) 507-9415; Email: Anne.Haroldsen@imail.org
• Study Contact Backup: Name: Mark Durst; Phone Number: 510-681-6862; Email: Mark.Durst@imail.org

Study Locations

• United States
  • Utah
    • Murray, Utah, United States, 84017
      • Intermountain Kidney Clinic
    • Murray, Utah, United States, 84107
      • Dialysis Services

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males and females (≥ 18 years of age) with End Stage Kidney Disease undergoing in-center hemodialysis
• 150 days of hemoglobin readings and Aranesp doses without a hospitalization relevant to the condition of anemia

Exclusion Criteria:

• Inflammation as characterized by ferritin levels greater than 1000 ng/mL
• Patients with active cancer
• Patients with PTH greater than 1,000 pg/mL
• Active GI Bleed
• Hospitalization relevant to ESRD in last 150 days or during study
• Patients receiving Procrit rather than Aranesp.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard of care; All patients placed on dialysis receive standard of care	Procedure: Standard of care; Current standard of care guidelines are followed for erythropoiesis-stimulating agents to control anemia in dialysis patients
Experimental: Model-based Aranesp doses; On entering the study cohort, patients will begin receiving doses calculated by the algorithm instead of by the standard of care procedures. Model-based Aranesp doses will be computed at the same time that doses based on the dialysis anemia protocol are determined. The model-based doses will be administered instead of the protocol-based doses and in the same way and at the same time as the protocol-based doses would have been.	Procedure: Algorithm model-based Aranesp doses; Patients will receive doses calculated by the algorithm instead of by the standard of care procedures. Model-based Aranesp doses will be computed at the same time that doses based on the dialysis anemia protocol are determined. The model-based doses will be administered instead of the protocol-based doses and in the same way and at the same time as the protocol-based doses would have been. The model-based dosing will be more flexible than the protocol-based dosing. Some constraints in the protocol-based dosing were created to prevent patients from achieving high Hb levels. The model-based dosing will also prevent these high Hb values but will do so by predicting a patient's Hb level into the future and then using these predictions to determine doses to reduce Hb variability and to reduce the amount of Aranesp used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of hemoglobin cycling in dialysis patients	Reduction of hemoglobin cycling	90 days after the intervention
Time hemoglobin levels are maintained within acceptable range	Time hemoglobin levels are maintained within acceptable range	90 days after the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in quantity of drug administered to patients	Reduction in quantity of drug administered to patients	90 days after the intervention

Collaborators and Investigators

• Sponsor: Intermountain Health Care, Inc.
• Investigators: Principal Investigator: Chemiti Gopal, MD, Intermountain Health Care, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: dialysis; kidney; darbepoetin; hemoglobin cycling
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: SMART Study (UHN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No