Clinical trial NCT05359263: Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKD
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Diseases
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
First posted: 2022-05-03
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in LV mass index assessed by echocardiography at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Change in LVEF assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Change in LA volume index assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Change in GLS assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Change in high sensitivity troponin I (hs-TNI) at 6 months
timeFrame: 6 months
measure: Change in N-terminal pro B-type natriuretic peptide (NT-pro-BNP) at 6 months
timeFrame: 6 months
measure: Change in estimated glomerular filtration rate (eGFR) 6 months
timeFrame: 6 months
measure: Change in urinary albumin-to-creatinine ratio (UACR) at 6 months
timeFrame: 6 months
measure: Change in hemoglobin at 6 months
timeFrame: 6 months
measure: Change in LV mass assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Change in LV end-diastolic volume at 6 months
timeFrame: 6 months
measure: Change in LV end-systolic volume at 6 months
timeFrame: 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Gentofte Hospital
Study officials:
affiliation: Research Director
name: Tor Biering-Sørensen
role: STUDY_CHAIR
References: