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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Other: Non-interventional

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 Type: Observational
• Enrollment (Actual): 85259

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development, Inc.; Phone Number: 800-888-7704; Email: Astellas.registration@astellas.com

Study Locations

• Germany
  • Bad Homburg, Germany, 61352
    • Site DE49001

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will be patients with anemia of CKD treated with ESA in stage 5D, i.e., on renal replacement therapy (RRT), including extracorporeal RRT and peritoneal dialysis (PD) prevalent as patients in Fresenius Medical Care (FME)'s Nephrocare centers and documented in the EuCliD data base between January 1st 2015 and December 31st 2021.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ESA hyporesponsive CKD patients; 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.	Other: Non-interventional; Epidemiology of anemia associated with chronic kidney disease, rather than to evaluate specific drugs
ESA responsive CKD patients; 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.	Other: Non-interventional; Epidemiology of anemia associated with chronic kidney disease, rather than to evaluate specific drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Part: Rate of ESA hyporesponsive events	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.	Up to 12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Actual): November 22, 2022
• Study Completion (Actual): November 22, 2022

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: September 5, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Chronic kidney disease; EuCliD; Erythropoietin hyporesponsiveness
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 1517-MA-3435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

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