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

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

Interventions

DRUG

Empagliflozin 10 MG

Oral administration

DRUG

Finerenone

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.

DEVICE

Withings BPM Connect

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.

DEVICE

Withings Body

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

DIAGNOSTIC_TEST

PeeSpot Urine Collection Device

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.

DIAGNOSTIC_TEST

Hem-Col Capillary Blood Collection Device

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.

BEHAVIORAL

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

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.

Sponsors & Collaborators

• Boehringer Ingelheim

  collaborator INDUSTRY

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• Hiddo Lambers Heerspink · University Medical Center Groningen

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-29

Primary Completion

2025-09-24

Completion

2025-09-24

FDA Drug

Yes

FDA Device

Yes

Countries

• Netherlands

Study Locations