Incidence and Clinical Burden of Erythropoietin Hyporesponsiveness - a Retrospective Database Analysis

Completed

• Conditions: Chronic Kidney Disease
• Interventions: Other: Non-interventional

• Registration Number: NCT05530291
• Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary

This study consists of two phases. The purpose of phase 1 is to identify incidence and patterns of erythropoiesis-stimulating agent (ESA) hyporesponsiveness and its associated factors in ESA treated patients. The purpose of phase 2 to identify outcomes associated with ESA hyporesponsiveness. Key aspects of the phase 2 study design will entirely depend on the results from phase 1.

Detailed Description

This is a retrospective database analysis of patients with anemia associated with chronic kidney disease (CKD) treated with ESAs from January 1st 2015 - December 31st 2021. Data will be derived from European Clinical Database (EuCliD).

Study Timeline

• Study First Submitted: 2022-09-05
• Study First Submitted QC: 2022-09-05
• Study First Posted: 2022-09-07
• Study Start: 2022-11-18
• Primary Completion: 2022-11-22
• Study Completion: 2022-11-22
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85259

Inclusion Criteria

All patients

• Patient has a diagnosis of chronic kidney disease valid between January 1st, 2015, and December 31st, 2021 and is documented in the EuCliD database (incident and prevalent patients)
• Patient who is treated with renal replacement therapy (RRT) (CKD Stage 5) during the study period
• Patient receiving erythropoiesis-stimulating agent (ESA) therapy, within the data collection period having EuCliD data available for a period of the previous 30 days before Index Date but not strictly limited to patients that enter the study period as ESA naïve patients
• Patient having provided consent for secondary use of their data for research purposes
• Patient has a known ESA administration route (intravenous/subcutaneous)
• Patient with a hemoglobin value available at baseline (+/- 20 days allowed) and at least one valid hemoglobin value afterwards
• Patient having at least one body weight value available

Hyporesponsive Cohort

• Patients meeting the hyporesponsive criteria on at least one occasion. The criteria for ESA hyporesponsive will follow the National Institute for Health and Care Excellence, UK (NICE) guidelines:

  • for epoetin alfa, 300 IU/kg/week or more of subcutaneous epoetin or 450 IU/kg/week or more of intravenous epoetin
  • for darbepoetin, dose ≥ 1.5 μg/kg per week

Responsive Cohort

• Patients with all ESA doses lower than those defined by the hyporesponsive criteria

Exclusion Criteria

• Patient with evidence of hereditary hemolytic anemia (International Classification of Diseases 10th Revision [ICD-10] code D58.9)
• Patient receiving transplant within 6 months prior to Index Date

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ESA hyporesponsive CKD patients	Non-interventional	A cohort of patients who meets ESA hyporesponsiveness criteria as well as other common criteria will be created from the Fresenius Medical Care´s proprietary clinical database called EuCliD.
ESA responsive CKD patients	Non-interventional	A cohort of patients who meets ESA responsiveness criteria as well as other common criteria will be created from the Fresenius Medical Care´s proprietary clinical database called EuCliD.

Primary Outcome Measures

Name	Time	Method
Phase 1 Part: Rate of ESA hyporesponsive events	Up to 12 months	The total number of patients with a new hyporesponsive event in relation to National Institute for Health and Care Excellence, UK (NICE) guidelines within a year after the ESA dose start will be counted as incidence. For deriving the incidence rate, the number of incidence cases will be divided by the sum of the time (days) each patient was observed within this group, totaled for all patients in this ESA subgroup.

Secondary Outcome Measures

Name	Time	Method
Phase 1 Part: Correlation of hyporesponsiveness and patient characteristics over time	Up to 12 months	Visual representation of hyporesponsiveness and patient characteristics (Hemoglobin \[Hb\] values, ESA dose, anemia treatment, and NICE defined Hyporesponsiveness) to assess relationship to one another.
Phase 1 Part: Time from the start of ESA dose to the first hyporesponsive event	Up to 12 months	The time until the first hyporesponsiveness event will be estimated.
Phase 1 Part: Characteristics on date of first incidence satisfying hyporesponsiveness criteria	Up to 12 months	Demographics and clinical characteristics of patients who developed ESA hyporesponse will be compared with a matched control group.
Phase 1 Part: Percentage of ESA hyporesponsiveness in relation to the KDIGO definition	At 12 months	Percentages in relation to the Kidney Disease: Improving Global Outcomes (KDIGO) definition will be provided for the ESA hypo-responders and the ESA responders.
Phase 1 Part: Distribution of ESA hyporesponsiveness patients	Up to 12 months	Hyporesponsive events will be categorized into isolated, intermittent and chronic, and distribution will be evaluated.
Phase 1 Part: Baseline characteristics	Day 1 (start of ESA treatment)	Demographics and clinical characteristics of patients who developed ESA hyporesponse and those that did not (responders) will be compared.
Phase 1 Part: Percentage of ESA hyporesponsiveness per Clinical Practicability Algorithm	At 12 months	Percentages per Clinical Practicability Algorithm will be provided for the ESA hyporesponders and the ESA responders.

Trial Locations

Locations (1)

Site DE49001; 🇩🇪 Bad Homburg, Germany