Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKD (DECODE-CKD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Dapagliflozin 10 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 222
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Niklas Dyrby Johansen; Phone Number: +4520204794; Email: niklas.dyrby.johansen@regionh.dk
• Study Contact Backup: Name: Katja Vu Bartholdy, MD; Phone Number: +4531360232; Email: katja.vu.bartholdy@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2900
    • Recruiting
    • Gentofte Hospital
    • Contact: Katja Vu Bartholdy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin 10 mg once daily	Drug: Dapagliflozin 10 mg; The intervention arm consists of dapagliflozin 10 mg orally once daily
Placebo Comparator: Placebo once daily	Drug: Placebo; The comparator arm consists of placebo orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in LV mass index assessed by echocardiography at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in LVEF 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 urinary albumin-to-creatinine ratio (UACR) at 6 months	6 months
Change in hemoglobin at 6 months	6 months
Change in LA volume index assessed by echocardiography 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MoCA score at 6 months	Cognitive impairment will be assessed using the change of the Montreal Cognitive Assessment (MoCA)	6 months
Change in Quality of Life at 6 months	Health-related quality of life will be quantified using the validated self-administered questionnaire the Kidney Disease Quality of Life questionnaire (KDQOL-36)	6 months
Change in HADS score at 6 months	Depressive symptoms will be assessed using The Hospital Depression and Anxiety Scale.	6 months

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Investigators: Study Chair: Tor Biering-Sørensen, Research Director

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Estimated): February 18, 2025
• Study Completion (Estimated): February 18, 2025

Study Registration Dates

• First Submitted: April 28, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: DECODE-CKD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No