Chronic Kidney Diseases
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDapagliflozin 10 mg
The intervention arm consists of dapagliflozin 10 mg orally once daily
DRUGPlacebo
The comparator arm consists of placebo orally once daily
Sponsors
Tor Biering-Sørensen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in LV mass index assessed by echocardiography at 6 months | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in LA volume index assessed by echocardiography at 6 months | 6 months |
| Change in GLS assessed by echocardiography at 6 months | 6 months |
| Change in high sensitivity troponin I (hs-TNI) at 6 months | 6 months |
| Change in N-terminal pro B-type natriuretic peptide (NT-pro-BNP) at 6 months | 6 months |
| Change in estimated glomerular filtration rate (eGFR) 6 months | 6 months |
| Change in LVEF assessed by echocardiography at 6 months | 6 months |
| Change in hemoglobin at 6 months | 6 months |
| Change in LV mass assessed by echocardiography at 6 months | 6 months |
| Change in LV end-diastolic volume at 6 months | 6 months |
| Change in LV end-systolic volume at 6 months | 6 months |
| Change in urinary albumin-to-creatinine ratio (UACR) at 6 months | 6 months |
Countries
Denmark
Contacts
Primary ContactKatja Vu Bartholdy, MD
Backup ContactNiklas Dyrby Johansen
Outcome results
None listed