A Study to Examine Past Estimated Glomerular Filtration Rate (eGFR) Slope as a Risk Marker for Rapid Kidney Function Decline in People With Chronic Kidney Disease

Evaluation of Homogeneity Between eGFR Slopes Derived From Retrospective Clinical Practice Data and eGFR Slopes Derived From Prospectively Collected, Protocol-driven Data

This study is intended to investigate the usefulness of estimated glomerular filtration rate (eGFR) slopes derived from retrospective routine clinical practice data, compare those retrospective slopes with those generated in a prospective fashion and successively identify rapidly progressing chronic kidney disease (CKD) patients.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Diagnostic test: collection of serum/capillary creatinine values

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Düsseldorf, Germany, 40210
    • DaVita Clinical Research Germany GmbH
  • Essen, Germany, 45136
    • InnoDiab Forschung GmbH
  • Geilenkirchen, Germany, 52511
    • DaVita Clinical Research Germany GmbH
• Hungary
  • Balatonfured, Hungary, 8230
    • DRC Drug Research Ltd
  • Budapest, Hungary, 1115
    • Szent Imre Korhaz, Budapest
• Spain
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants, LLC
  • California
    • Victorville, California, United States, 92395
      • Kidney & Hypertension Center
    • Victorville, California, United States, 92392
      • Desert Cities Dialysis - Amethyst
  • Connecticut
    • Bloomfield, Connecticut, United States, 06002
      • Davita Clinical Research-Hartford
    • Middlebury, Connecticut, United States, 06762-2843
      • Nephrology & Hypertension Assoc., PC
  • Florida
    • Miami, Florida, United States, 33183
      • International Research Associates
    • Miami, Florida, United States, 33125
      • Med-Care Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
  • Minnesota
    • Edina, Minnesota, United States, 55435-2129
      • DaVita Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • DaVita Clinical Research
  • New York
    • Bronx, New York, United States, 10461
      • Kidney Medical Associates, PLLC
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306
      • DaVita Clinical Research (DCR) Spartanburg
  • Texas
    • El Paso, Texas, United States, 79925
      • DaVita Clinical Research
    • Greenville, Texas, United States, 75402-6004
      • Sunbeam Clinical Research
    • Houston, Texas, United States, 77054
      • DaVita Clinical Research
    • San Antonio, Texas, United States, 78251
      • DaVita Clinical Research
    • The Woodlands, Texas, United States, 77384
      • DaVita Clinical Research
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Tidewater Kidney Specialists
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • DaVita Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Manufacturing Practice (ICH-GCP) and local legislation prior to admission to the trial.
2. Patients with available medical records for data abstraction to meet the objectives of the study.
3. Male or female patients aged ≥ 18 years at time of consent.
4. Body Mass Index (BMI) ≥ 18.5 and < 50 kg/m² at Visit 1.
5. Clinical diagnosis of Chronic Kidney Disease (CKD).
6. Estimated Glomerular Filtration Rate (eGFR) decline of at least 1ml/min/1.73m²/year based on historical data from (electronic) medical records.
7. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) 20 - 90 ml/min/1.73m² at Visit 1 calculated from serum creatinine measured by a central laboratory.
8. Patients are expected to be on optimal and stable background treatment (according to local therapy guidelines).

9. At least 4 serum creatinine values in the retrospective phase:

   • The most recent creatinine value not more than 6 months prior to Visit 1 (Screening Visit).
   • The most recent and oldest serum creatinine values should be no less than 1 year apart and no greater than 5 years apart.
   • There should be no gap of creatinine values of 2 years or longer.

Exclusion Criteria:

1. Changes in CKD or other key background treatments (including dose changes) known to impact eGFR values, over the past 4 weeks for Angiotensin Converting Enzyme inhibitors (ACEis) and Angiotensin Receptor Blockers (ARBs) and 8 weeks for Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors prior to Screening.
2. Autosomal Dominant Polycystic Kidney Disease (ADPKD), uncontrolled lupus nephritis, in the opinion of investigators.
3. Any iv immune suppression therapy within the last 3 months prior to Visit 1 or anyone currently on >45 mg prednisolone (or equivalent).
4. Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition in the 30 days prior to Visit 1 until the start of trial assessments.
5. Planned start of chronic renal replacement therapy during the trial or end stage renal disease (i.e < 15 ml/min at 2 measurements 30 days apart) before start of trial assessments.
6. Medical history of cancer or treatment for cancer in the last two years prior to Visit 1 (except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, and prostatic cancer of low grade [T1 or T2]).
7. Major surgery (investigator's judgement) planned during the trial.
8. Currently enrolled in an investigational device or drug trial, i.e., less than 30 days before Visit 1 since ending an investigational device or drug trial(s) or receiving investigational treatment(s).

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with chronic kidney disease - overall population; Patients with chronic kidney disease (CKD), including patients with non-diabetic chronic kidney disease (non-DKD) and diabetic kidney disease (DKD). Participants in this study did not receive any medication or study drug.	Diagnostic test: collection of serum/capillary creatinine values; collection of serum/capillary creatinine values

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Homogeneity (eGFR Slope Shift Table) Between eGFR Slopes Derived From Retrospective and Prospective eGFR Values	Retrospective and prospective slopes were derived using a linear random slope model. The prospective estimated Glomerular Filtration Rate (eGFR) slope for each patient was derived using eGFR values in the prospective phase as the dependent variable and time in the prospective phase as the continuous independent variable with random intercept and random slope. The retrospective eGFR slope for each patient was derived similarly using the data in the retrospective phase, and the time in the retrospective phase calculated relative to the first retrospective measurement per patient. Homogeneity was primarily evaluated via a shift analysis with categories of eGFR decline rate of 1 to < 3 (slow) and >= 3 ml/min/1.73m2/year (fast), in each of the retrospective and prospective phases. eGFR data collected 4 weeks before acute kidney injury and up to 8 weeks after acute kidney injury, and eGFR data occurring after changes to baseline background therapy (SGLT2i/ACEi/ARB) were excluded.	Prospective slopes: All measurements from baseline until the last available visit were considered for inclusion in the estimation, including unscheduled visits, up to 48 weeks. Retrospective slopes: up to 66 months.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• 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: 1366-0026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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