Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKD

Официальное название

A 6-Month, Randomized, Double-Blind Study to Evaluate the Effect of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease

Обзор

The purpose of this study is to investigate the effects of dapagliflozin on echocardiographic measures of cardiac structure and function in patients with chronic kidney disease.

Подробное описание

The study is a 6-month, investigator-initiated, randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of dapagliflozin on echocardiographic measures of cardiac structure and function in patients with chronic kidney disease. The study population will consist of approximately 222 adults with chronic kidney disease - defined as a glomerular filtration rate (GFR) of 20-60 mL/min/1.73m2, in treatment with maximally tolerated ACEi or ARB. Patients will be randomized to either 10 mg dapagliflozin or placebo. Patients will be assessed by measurement of echocardiography, pulse wave velocity, blood samples, urine samples, quality of life, depressive symptoms, and cognitive function at baseline and after 6 months of treatment.

Вмешательства

• Препарат Dapagliflozin 10 mg
  The intervention arm consists of dapagliflozin 10 mg orally once daily
• Препарат Placebo
  The comparator arm consists of placebo orally once daily

Первичные конечные точки

• Change in LV mass index assessed by echocardiography at 6 months [Срок оценки: 6 months]

Вторичные конечные точки (11)

• Change in LVEF assessed by echocardiography at 6 months [Срок оценки: 6 months]
• Change in LA volume index assessed by echocardiography at 6 months [Срок оценки: 6 months]
• Change in GLS assessed by echocardiography at 6 months [Срок оценки: 6 months]
• Change in high sensitivity troponin I (hs-TNI) at 6 months [Срок оценки: 6 months]
• Change in N-terminal pro B-type natriuretic peptide (NT-pro-BNP) at 6 months [Срок оценки: 6 months]
• Change in estimated glomerular filtration rate (eGFR) 6 months [Срок оценки: 6 months]
• Change in urinary albumin-to-creatinine ratio (UACR) at 6 months [Срок оценки: 6 months]
• Change in hemoglobin at 6 months [Срок оценки: 6 months]
• Change in LV mass assessed by echocardiography at 6 months [Срок оценки: 6 months]
• Change in LV end-diastolic volume at 6 months [Срок оценки: 6 months]
• Change in LV end-systolic volume at 6 months [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Signed informed consent
• ≥ 18 years of age
• Chronic kidney disease (CKD), defined as evidence of decreased eGFR (eGFR ≥20 and <60 mL/minute per 1.73 m2) or between eGFR ≥60 and <90 mL/minute per 1.73 m2 with urinary albumin:creatinine ratio ≥200 mg/g or protein:creatinine ratio ≥300 mg/g
• Stable treatment with clinically appropriate doses of ACEi/ARB among CKD patients with proteinuria and uptitrated to maximal recommended or tolerated dose for at least 4 weeks before randomization, if not medically contraindicated
• For patients with type 2 diabetes:

Stable antihyperglycemic treatment > 30 days before screening

• Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device
• Ability to understand and read Danish

Критерии исключения

• Type 1 diabetes
• For patients with type 2 diabetes:

History of diabetic ketoacidosis

• Patients undergoing dialysis
• History of organ transplant
• Treatment with SGLT2 inhibitor within 8 weeks prior to enrolment
• Known allergy or hypersensitivity to SGLT2 inhibitors or Placebo ingredients
• Myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks of enrolment
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment
• Any condition outside the renal and cardiovascular study area with a life expectancy of <2 years based on investigator's clinical judgement
• Hepatic impairment (aspartate transaminase or alanine transaminase >3 times the upper limit of normal \[ULN\] or total bilirubin >2 times the ULN at the time of enrolment)
• Known blood-borne diseases, such as Hepatitis A, B, C, D, and E, and Human immunodeficiency virus (HIV) types 1 and 2, Ebola, Lassa fever virus.
• Female patients who are pregnant, lactating, or are considering becoming pregnant during the study or for 6 months after study completion
• Participation in another clinical study with an investigational product within the last month prior to enrolment
• Inability to understand or comply with the investigational product, procedures, and/or follow-up or any conditions that may prevent the participant to complete the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• Gentofte Hospital — Copenhagen

Публикации

• Bartholdy KV, Johansen ND, Skaarup KG, Modin D, Landler N, Langhoff AF, Ottosen CI, Espersen C, Dons M, Borchsenius JIM, Davodian LW, Lassen MH, Davidovski FS, Jensen AMR, Sengelov M, Christensen J, Schou M, Feldt-Rasmussen B, Jensen J, Bressendorff I, Persson F, Rossing P, Kober L, Zannad F, Vaduganathan M, Solomon S, Haynes R, Hansen D, Biering-Sorensen T. Cardiac Effects of Dapagliflozin in Peo PMID 41147829
• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2. PMID 38770818
• Bartholdy KV, Johansen ND, Landler N, Skaarup KG, Jensen J, Bressendorff I, Schou M, Christensen J, Feldt-Rasmussen B, Vaduganathan M, Solomon S, Haynes R, Persson F, Rossing P, Kober L, Zannad F, Hansen D, Biering-Sorensen T. Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease: The DECODE-CKD Trial. Kidney360. 2023 Feb 1 PMID 36649484

Идентификаторы

NCT: NCT05359263 · DECODE-CKD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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