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

Chronic Kidney Diseases Clinical Trial

— DECODE-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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05359263
• Other study ID #: DECODE-CKD
• Status: Recruiting
• Phase: Phase 2
• Start date: June 8, 2022
• Est. completion date: April 15, 2025

Study information

• Verified date: December 2022
• Source: Herlev and Gentofte Hospital
• Contact: Katja Vu Bartholdy, MD
• Phone: +4531360232
• Email: katja.vu.bartholdy[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: April 15, 2025
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent

• = 18 years of age

• Chronic Kidney Disease (CKD), defined as evidence of decreased eGFR (eGFR >20 and <60 mL/min/1.73 m2) at least 3 months before and at the time of screening

• 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

• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment

• 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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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

Locations

Country	Name	City	State
Denmark	Gentofte Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Tor Biering-Sørensen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in MoCA score at 6 months	Cognitive impairment will be assessed using the change of the Montreal Cognitive Assessment (MoCA)	6 months
Other	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
Other	Change in HADS score at 6 months	Depressive symptoms will be assessed using The Hospital Depression and Anxiety Scale.	6 months
Primary	Change in LV mass index assessed by echocardiography at 6 months		6 months
Secondary	Change in LV dimensions assessed by echocardiography at 6 months		6 months
Secondary	Change in LVEF assessed by echocardiography at 6 months		6 months
Secondary	Change in E-wave assessed by echocardiography at 6 months		6 months
Secondary	Change in A-wave assessed by echocardiography at 6 months		6 months
Secondary	Change in E/e' assessed by echocardiography at 6 months		6 months
Secondary	Change in E/A ratio assessed by echocardiography at 6 months		6 months
Secondary	Change in LA volume assessed by echocardiography at 6 months		6 months
Secondary	Change in GLS assessed by echocardiography at 6 months		6 months
Secondary	Change in LA strain assessed by echocardiography at 6 months		6 months
Secondary	Change in RV strain assessed by echocardiography at 6 months		6 months
Secondary	Change in high sensitivity troponin I (hs-TNI) at 6 months		6 months
Secondary	Change in Soluble suppression of tumorigenicity 2 (sST2) at 6 months		6 months
Secondary	Change in N-terminal pro B-type natriuretic peptide (NT-pro-BNP) at 6 months		6 months
Secondary	Change in necrosis factor a (TNF-a) at 6 months		6 months
Secondary	Change in copeptin at 6 months		6 months
Secondary	Change in high sensitivity C-reactive protein (hs-CRP) at 6 months		6 months
Secondary	Change in estimated glomerular filtration rate (eGFR) 6 months		6 months
Secondary	Change in serum potassium at 6 months		6 months
Secondary	Change in serum neutrophil gelatinase-associated lipocalin (sNGAL) at 6 months		6 months
Secondary	Change in urinary neutrophil gelatinase-associated lipocalin (uNGAL) at 6 months		6 months
Secondary	Change in urinary kidney injury molecule-1 (KIM-1) at 6 months		6 months
Secondary	Change in insulin growth factor-binding protein-7 (IGFBP7) at 6 months		6 months
Secondary	Change in serum cystatin C at 6 months		6 months
Secondary	Change in uric acid at 6 months		6 months
Secondary	Change in urinary albumin-to-creatinine ratio (UACR) at 6 months		6 months
Secondary	Change in erythropoietin (EPO) at 6 months		6 months
Secondary	Change in estimated plasma volume at 6 months		6 months
Secondary	Change in hemoglobin at 6 months		6 months
Secondary	Change in hemotocrit at 6 months		6 months
Secondary	Change in ferritin at 6 months		6 months
Secondary	Change in transferrin at 6 months		6 months
Secondary	Change in iron at 6 months		6 months
Secondary	Change in calcium at 6 months		6 months
Secondary	Change in phosphate at 6 months		6 months
Secondary	Change in magnesium at 6 months		6 months
Secondary	Change in PTH at 6 months		6 months
Secondary	Change in fibroblast growth factor 23 (FGF-23) at 6 months		6 months
Secondary	Change in calcification propensity (T50) at 6 months		6 months
Secondary	Change in fetuin-A (fetA) at 6 months		6 months
Secondary	Change in bicarbonate at 6 months		6 months
Secondary	Change in klotho at 6 months		6 months
Secondary	Change in urine sodium at 6 months		6 months
Secondary	Change in urine glucose at 6 months		6 months
Secondary	Change in hemoglobin A1C at 6 months		6 months
Secondary	Changein central blood pressure assessed by pulse wave analysis at 6 months		6 months
Secondary	augmentation index assessed by pulse wave analysis at 6 months		6 months