Optimization of Albuminuria-Lowering Therapies for Individual Patients With Type 2 Diabetes Using Empagliflozin and Finerenone in a Pilot Remote Clinical Trial.

University Medical Center Groningen1 个研究点分布在 1 个国家目标入组 12 人开始时间: 2024年7月29日最近更新: 2026年2月13日

适应症

干预措施

试验速览

阶段: 4 期
状态: 已完成
发起方: University Medical Center Groningen
入组人数: 12
试验地点: 1
主要终点: Questionnaire results

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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)

详细描述

Rationale:

The treatment of cardiovascular and kidney-related complications associated with type 2 diabetes has made significant progress in recent years. Clinical trials have demonstrated the clinical benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors and the selective non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone. Guidelines from professional nephrology and cardiology associations now recommend the use of SGLT2 inhibitors and finerenone for all patients with type 2 diabetes and chronic kidney disease (CKD). Although guidelines recommend the use of these new drug classes for all patients, the adoption in clinical practice has been slow, with implementation barriers existing at the healthcare facility, physician, and patient levels.

Despite the beneficial effects of these new drug classes on a population level, resulting in a reduction in the relative risks of cardiovascular and kidney outcomes, a high residual risk remains, which is closely associated with high levels of albuminuria. This remaining risk can, in part, be attributed to sub-optimal individual responses to SGLT2 inhibitors and finerenone. The investigators' previous research has demonstrated substantial variability in individual albuminuria responses to SGLT2 inhibitors and MRAs among patients, indicating that some patients benefit from SGLT2 inhibitors, others from finerenone, and yet another group requires a combination of both agents for optimal cardiovascular and kidney protection.

To leverage technological advancements and evaluate drug efficacy and safety at an individual patient level, the investigators propose a pilot remote (home-based) clinical trial aimed at demonstrating the feasibility and advantages of conducting a remote clinical trial involving multiple medications to identify optimal therapy with the least pill burden for each patient. This trial will also assess patient experiences with data collection conducted remotely. This would potentially help (1) to facilitate the implementation of guideline-recommended treatments, (2) to optimize the guideline-recommended treatments for each individual, and (3) to evaluate individual drug responses and tailor therapy to each patient. Ultimately, the investigators' goal is to transition patient care from clinical settings (hospitals or general practitioner practices) to the home environment, making treatment regimen adjustments based on remotely collected data. This shift aims to minimize patient visits and enhance patient participation in optimizing their therapy in line with established guidelines.

Objective:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Crossover
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 65+ years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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:
•History of active inflammatory bowel disease within the last 6 months
•Major gastrointestinal tract surgery as decided by the physician.
•Pancreatitis within the last 6 months
•Gastrointestinal ulcers and/or bleeding within the last 6 months
•Evidence of urinary obstruction or difficulty in voiding at screening
•Participation in any clinical trial within 3 months prior to initial dosing
•Donation or loss of ≥400 mL of blood within 8 weeks prior to initial dosing
•Confirmed lactose intolerance demonstrated with a lactose intolerance test.
•History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening or according to investigator's assessment.
•History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
•Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
•Women of childbearing potential (WOCBP):
•WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of the study drug in such a manner the risk of pregnancy is minimised.
•WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent of HCG) at screening.
•WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below). The following women are NOT considered as WOCBP:
•Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
•Women who are practicing abstinence.
•Women who have a partner who is sterile (e.g. due to vasectomy).
•Post-menopause is defined as:
•Women who have had amenorrhea for >12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level >35 mIU/mL.
•Women who have irregular menstrual periods and a documented serum FSH level >35 mIU/mL.
•Women who are taking hormone replacement therapy (HRT).