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

• ClinicalTrials.gov Identifier: NCT04881448
• Recruitment Status: Terminated
• First Posted: May 11, 2021
• Results First Posted: August 4, 2023
• Last Update Posted: August 4, 2023
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: May 4, 2021
• First Posted Date: May 11, 2021
• Results First Submitted Date: July 14, 2023
• Results First Posted Date: August 4, 2023
• Last Update Posted Date: August 4, 2023
• Actual Study Start Date: September 16, 2021
• Actual Primary Completion Date: July 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2023)

Homogeneity (eGFR Slope Shift Table) Between eGFR Slopes Derived From Retrospective and Prospective eGFR Values [ Time Frame: 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. ]

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.

• Original Primary Outcome Measures (submitted: May 10, 2021): Homogeneity (eGFR slope shift table) between eGFR slopes derived from retrospective and prospective eGFR values [ Time Frame: up to 54 months ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: Evaluation of Homogeneity Between eGFR Slopes Derived From Retrospective Clinical Practice Data and eGFR Slopes Derived From Prospectively Collected, Protocol-driven Data
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Chronic Kidney Disease

Intervention

Diagnostic Test: collection of serum/capillary creatinine values

collection of serum/capillary creatinine values

Study Arms

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.

Intervention: Diagnostic Test: collection of serum/capillary creatinine values

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 14, 2023): 223
• Original Estimated Enrollment (submitted: May 10, 2021): 600
• Actual Study Completion Date: July 15, 2022
• Actual Primary Completion Date: July 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Hungary, Spain, United States

Administrative Information

• NCT Number: NCT04881448
• Other Study ID Numbers: 1366-0026
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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'.
• URL: https://www.mystudywindow.com/msw/datasharing

• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Same as current
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: July 2023