Treatment Optimization for Patients With Type 2 Diabetes Using Empagliflozin and Finerenone in a Remote Clinical Trial

NCT06094920 | Completed Phase 4 FDA Drug FDA Device

• 1 other identifier: 18253
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the feasibility of remote clinical trial conduct in patients with type 2 diabetes and elevated albuminuria. The main questions it aims to answer are:

• What is the feasibility (and advantages) of remote clinical trial conduct with multiple medications in patients with type 2 diabetes and elevated albuminuria?
• What is the individual response to the SGLT2 inhibitor empagliflozin in urine albumin-creatinine ratio?
• What is the individual response to the SGLT2 inhibitor empagliflozin in systolic blood pressure, body weight, eGFR, and fasting plasma glucose?
• Can suboptimal treatment responses to empagliflozin be overcome by the addition or substitution with finerenone? Participants will collect all study data in the comfort of their own environments
• First-morning void urine samples
• Capillary blood samples
• Blood pressure
• Body weight Participants will be assigned to a 3-week treatment period with empagliflozin 10 mg/day. Based on the albuminuria response after 2 weeks, participants will be allocated to one of three treatment regimens after the 3-week treatment period with empagliflozin:
• Continue empagliflozin for 4 more weeks (good response).
• Continue empagliflozin for 4 more weeks and add finerenone 10 or 20 mg will be added for 4 weeks (moderate response).
• Stop empagliflozin and start finerenone 10 or 20 mg for 4 weeks (no response)

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetes; Diabetes Complications; Albuminuria; Chronic Kidney Diseases; Chronic Kidney Disease stage3; Chronic Kidney Disease stage4; CKD; CKD Stage 3; CKD Stage 4; Diabetes Mellitus Type 2 With Proteinuria; Chronic Kidney Disease Due to Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes; Diabetes Mellitus, Type 2; Albuminuria; Diabetes Mellitus; Diabetes Mellitus Type 2 with Proteinuria; Personalized Medicine; Decentralized; Remote clinical trial; Remote data collection; Individualized; Treatment optimalization; CKD; Chronic Kidney Disease; Albuminuria-Lowering Therapies; Empagliflozin; Finerenone; SGLT2 inhibitors; MRA; Sodium Glucose Co-Transporter 2; Mineralocorticoid Receptor Antagonist

Outcome Measures

Primary Outcomes (5)

• Questionnaire results

  Participants' perspectives toward the feasibility of participation in a trial at home with digital technologies

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Remote urine collection

  Number and percentage of urine collections not received at the laboratory or unable to be analysed

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Remote blood pressure measurements

  Number and percentage of missed blood pressure measurements

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Remote body weight measurements

  Number and percentage of missed body weight measurements

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Treatment adherence

  Pill count and medication concentration in urine samples

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

Secondary Outcomes (10)

• Individual UACR response to empagliflozin

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Individual systolic blood pressure response to empagliflozin

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Individual body weight response to empagliflozin

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Individual eGFR response to empagliflozin

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

• Individual fasting plasma glucose response to empagliflozin

  Will be assessed within 6 months and reported within 1 year after conclusion of the study.

Study Arms (3)

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day

OTHER

Albuminuria reduction \>30% and the remaining albuminuria level is \<30 mg/g: continue empagliflozin 10 mg/day for an additional four weeks.

Drug: Empagliflozin 10 MG; Device: Withings BPM Connect; Device: Withings Body; Diagnostic Test: PeeSpot Urine Collection Device; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Behavioral: Questionnaire: participants' perspectives toward the feasibility of participation in a trial at home with digital technologies

B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day

OTHER

Albuminuria reduction \>30% or \>0 and ≤30%, and the remaining albuminuria level is \>30 mg/g: continue empagliflozin 10 mg/day for an additional four weeks and intensify treatment by adding finerenone 10 or 20 mg/day for four weeks (dosage depends on eGFR levels).

Drug: Empagliflozin 10 MG; Drug: Finerenone; Device: Withings BPM Connect; Device: Withings Body; Diagnostic Test: PeeSpot Urine Collection Device; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Behavioral: Questionnaire: participants' perspectives toward the feasibility of participation in a trial at home with digital technologies

C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

OTHER

No albuminuria reduction or increase: discontinue empagliflozin and switch to finerenone 10 or 20 mg/day for four weeks (dosage depends on eGFR levels).

Drug: Finerenone; Device: Withings BPM Connect; Device: Withings Body; Diagnostic Test: PeeSpot Urine Collection Device; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Behavioral: Questionnaire: participants' perspectives toward the feasibility of participation in a trial at home with digital technologies

Interventions

Empagliflozin 10 MG DRUG

Oral administration

Also known as: Jardiance, A10BK03, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day

Finerenone DRUG

Oral administration. Finerenone treatment may be initiated if serum potassium levels are ≤5.0 mmol/L. Conversely, if serum potassium levels are \>5.0 mmol/L, the initiation of finerenone treatment should be avoided. In such cases, a second serum potassium measurement will be performed two days later. If serum potassium levels are ≤5.0 mmol/L, these patients can still be considered for inclusion. However, if serum potassium levels are \>5.0 mmol/L again, these patients will be excluded, and an assessment of the underlying cause(s) of hyperkalaemia will be conducted. The recommended initial dose of finerenone is determined based on eGFR, which will be assessed prior to the commencement of the trial. If eGFR is ≥60 mL/min/1.73m2, the dose will be set at 20 mg once daily. If eGFR is ≥25 to \<60, the dose will be set at 10 mg once daily. Participants with an eGFR \<25 are not advised to undergo finerenone treatment and will be excluded from the study.

Also known as: Kerendia, C03DA05, (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide

B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

Withings BPM Connect DEVICE

CE marked and clinically validated blood pressure monitor. Clinical trial results are within the margin of acceptance defined by the internationally recognized evaluation standard of blood pressure monitors ANSI/AAMI/ISO 81060-2:2013, EN ISO 81060-2:2014, developed by the European Society of Hypertension, British Hypertension Society and Association for the Advancement of Medical Instrumentation/American Heart Association. Blood pressure will be measured by the participants once daily on 40 days. Three consecutive measurements are taken.

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

Withings Body DEVICE

CE marked and clinically validated advanced Wi-Fi smart scale. Body weight will be measured by the participants once daily on 49 days.

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

Hem-Col Capillary Blood Collection Device DIAGNOSTIC_TEST

Capillary blood samples will be obtained using a BD Microtainer® Contact-Activated Lancet (Franklin Lakes, New Jersey, USA) once daily on 17 days. These blood samples will be collected into Hem-Col® tubes (Hem-Col, Labonovum, Limmen, the Netherlands), specifically designed for collection of capillary blood acquired through a finger prick. The Hem-Col microtube is equipped with an anticoagulant and a preservation buffer, enhancing the stability of analytes in whole blood. These Hem-Col tubes have the dimensions of standard blood collection tubes and are constructed from polyethylene, featuring a pierceable cap made of thermoplastic elastomers. Each tube incorporates a liquid barrier, with the inner part preventing the loss of Hem-Col preservation fluid and the outer part serving as a scoop for collecting blood from a finger prick. The Hem-Col lithium heparin tubes will be utilized for the analysis of creatinine, potassium, hsCRP, haematocrit, cystatin C, and fasting plasma glucose.

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

PeeSpot Urine Collection Device DIAGNOSTIC_TEST

Biochemical urine data will be collected using first-morning void urine samples. Participants will obtain urine samples with the PeeSpot device, a validated tool designed for the collection and preservation of small urine volumes. This device comprises a urine absorption pad, a holder, a tube, and a lid. Patients can void directly onto the absorption pad while it is placed in the holder. Following voiding, the pad and holder are inserted into the tube, sealed with the lid, and stored in a refrigerator until they are sent to the laboratory using a biological materials envelope (PolyMed, DaklaPack, Europe). Through the incorporation of an inert hygroscopic polymer, the pad efficiently absorbs 1.2 mL of urine, and with the addition of various preservatives, the urine remains stable for up to four days. The investigators will employ the PeeSpot to determine the first-morning void levels of albumin, creatinine, sodium, potassium, glucose, urea, and osmolality once daily on 28 days.

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

Questionnaire: participants' perspectives toward the feasibility of participation in a trial at home with digital technologies BEHAVIORAL

Participant perspectives regarding the feasibility of participating in a home-based trial will be evaluated using a digital questionnaire. This questionnaire includes inquiries adapted from the validated Telehealth Usability Questionnaire, supplemented with additional questions employed in prior studies that assessed the feasibility of decentralized clinical trials. The web application Research Electronic Data Capture 10.0.23 (REDCap - www.projectredcap.org) will facilitate the administration of these digital questionnaires. Participants will receive a link to access the digital questionnaires via email. Weekly telephone calls will be conducted to evaluate adherence to study procedures and monitor the occurrence of adverse events.

A. Good albuminuria response after 2 weeks empagliflozin 10 mg/day; B. Moderate albuminuria response after 2 weeks empagliflozin 10 mg/day; C. No albuminuria reduction after 2 weeks empagliflozin 10 mg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Diagnosis of type 2 diabetes
• UACR \>4.5 mg/mmol (\>40 mg/g) and ≤300 mg/mmol (≤2655 mg/g)
• eGFR ≥25 mL/min/1.73m2
• On a stable dose of an ACE inhibitor/ARB if tolerated
• Willing to sign informed consent.
• Proficiency in the Dutch language

You may not qualify if:

• Diagnosis of type 1 diabetes
• Already treated with any SGLT2 inhibitor or MRA
• Unable to monitor blood pressure or body weight or handle digital technologies.
• Heart failure New York Heart Association (NYHA) Class II to IV requiring MRA treatment
• Acute coronary syndrome event within 6 months
• Serum potassium \>5 mmol/L repeat value after repeated measurement
• Evidence of severe hepatic impairment determined by any of one: ALT or AST values exceeding 3 times ULN, a history of hepatic encephalopathy, a history of oesophageal varices, or a history of portocaval shunt.
• Active pregnancy or breastfeeding
• History of kidney or liver transplant
• Unstable or rapidly progressing renal disease.
• Active malignancy
• Suggestive evidence of adrenal insufficiency
• History of severe hypersensitivity or contraindications to any SGLT2 inhibitor or MRA
• Uncontrolled arterial hypertension (mean sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg)
• Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:

Sponsors & Collaborators

• Boehringer Ingelheim: collaborator
• University Medical Center Groningen: lead

Study Sites (1)

ZorgGroep Twente

Almelo, Overijssel, 7609PP, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetes Complications; Albuminuria; Renal Insufficiency, Chronic

Interventions

empagliflozin; finerenone; Digital Technology

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Technology; Technology, Industry, and Agriculture

Study Officials

• Hiddo Lambers Heerspink

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible participants will be assigned to a 3-week treatment period with the SGLT2 inhibitor empagliflozin 10 mg/day, in accordance with guidelines. After 2 weeks, albuminuria levels will be assessed to determine the individual albuminuria response. Depending on the response (decrease or increase), participants will be allocated to one of three treatment regimens following the 3-week empagliflozin treatment period: A. Albuminuria reduction \>30% and the remaining albuminuria level is \<30 mg/g: continue empagliflozin for an additional four weeks. B. Albuminuria reduction \>30% or \>0 and ≤30%, and the remaining albuminuria level is \>30 mg/g: continue empagliflozin for an additional four weeks and intensify treatment by adding finerenone for four weeks. C. No albuminuria reduction or increase: discontinue empagliflozin and switch to finerenone for four weeks.

Study Record Dates

• First Submitted: October 11, 2023
• First Posted: October 23, 2023
• Study Start: July 29, 2024
• Primary Completion: September 24, 2025
• Study Completion: September 24, 2025
• Last Updated: February 13, 2026

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)