Vascular Impact of Dapagliflozin in CKD Patients (DAPAVASC)
- Conditions
- Renal Insufficiency, Chronic
- Interventions
- Drug: PlaceboProcedure: impedance cardiographyProcedure: Applanation tonometryProcedure: post-ischemic hyperemia of forearmProcedure: haemodynamics parameters
- Registration Number
- NCT04930549
- Lead Sponsor
- University Hospital, Rouen
- Brief Summary
This study aims to determine whether dapaglfiflozin 12-week administration is associated with a beneficial impact on the vasculature of patients with chronic kidney disease.
- Detailed Description
A prospective, randomized, double-blind studies evaluating the impact of once-daily dapagliflozin 10 mg versus placebo for 12 weeks on endothelial function, as primary endpoint, will be conducted in 56 patients with chronic kidney disease (eGFR ≥25 and ≤60 mL/min/1.73m2 by CKD-EPI) and without diabetes (fasting glycemia≥1.26 mg/dL, oral hypoglycemic agents or insulin) on top of standard treatment (n=27 per group). Indexes of arterial stiffness, cardiovascular coupling, cardiac function and plasma concentrations of endothelial, inflammatory and oxidative stress biomarkers will be assessed as secondary endpoints. Patients will be recruited in the Departments of Cardiology and Nephrology of Rouen University Hospital. The study will include an inclusion visit (V1), 2 exploration visits performed before (V2) and 12 weeks (V3) after treatment initiation, and 1 output study (V4).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 54
- Chronic kidney disease (eGFR ≥25 and ≤60 mL/min/1.73m² by CKD-EPI)
- Age ≥ 18 years
- Receiving a stable dose of an ACE inhibitor or ARB for at least 12 weeks before screening or patients who were documented to be intolerant to ACE inhibitors or ARBs
- Type 1 and type 2 diabetes (fasting glycemia≥126 mg/dL or use of oral hypoglycemic agents or insulin)
- Recessive or autosomal dominant polycystic kidney disease
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
- Lupus nephritis
- Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
- History of organ transplantation
- Body weight > 35 kg/m²
- Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
- Patients with NYHA class IV congestive heart failure at the time of enrolment
- Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
- Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
- Active malignancy requiring treatment at the time of enrolment or is planned to undergo any treatment after randomization
- Severe hepatic impairment (Child-Pugh class C)
- History of frequent genital mycotic infections (>2)
- Current pregnancy OR women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or exploration visits OR women who are breast-feeding
- Contraindications to use glyceryl trinitrate (in particular allergy to nitrates or concomitant use of vasodilators)
- Participation in another clinical study with an investigational product during the last month prior to enrolment
- Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dapagliflozin 10Mg Tab impedance cardiography Dapagliflozin 10 mg film-coated tablets Dapagliflozin 10Mg Tab Dapagliflozin 10Mg Tab Dapagliflozin 10 mg film-coated tablets Dapagliflozin 10Mg Tab Applanation tonometry Dapagliflozin 10 mg film-coated tablets Dapagliflozin 10Mg Tab post-ischemic hyperemia of forearm Dapagliflozin 10 mg film-coated tablets Dapagliflozin 10Mg Tab haemodynamics parameters Dapagliflozin 10 mg film-coated tablets Placebo Placebo Identical film-coated tablets without dapagliflozin Placebo impedance cardiography Identical film-coated tablets without dapagliflozin Placebo Applanation tonometry Identical film-coated tablets without dapagliflozin Placebo post-ischemic hyperemia of forearm Identical film-coated tablets without dapagliflozin Placebo haemodynamics parameters Identical film-coated tablets without dapagliflozin
- Primary Outcome Measures
Name Time Method Change from baseline of brachial artery endothelial function using echography 12 weeks Change in brachial artery flow-mediated dilatation in response to post-ischemia hyperemia using difference of brachial artery diameter
- Secondary Outcome Measures
Name Time Method Change from baseline of arterial stiffness using applanation tonometry 12 weeks Change in carotid-to-femoral pulse wave velocity
Change from baseline of carotid artery geometry using echography (2) 12 weeks Change in carotid intima-media thickness using echography
Change from baseline of cardiac function by impedance cardiography (2) 12 weeks Change in stroke volume
Change from baseline of cardiac function by impedance cardiography (6) 12 weeks Change in left ventricular end-systolic elastance
Change from baseline of carotid artery geometry using echography (1) 12 weeks Change in carotid diastolic diameter
Change from baseline of cardiac function by impedance cardiography (1) 12 weeks Change in cardiac output
Change from baseline of cardiac function by impedance cardiography (3) 12 weeks Change in ejection fraction
Change from baseline of cardiac function by impedance cardiography (4) 12 weeks Change in end-diastolic volume
Change from baseline of cardiac function by impedance cardiography (5) 12 weeks Change in total peripheral resistance,
Change from baseline of epoxyeicosatrienoic acid bioavailability 12 weeks Change in epoxyeicosatroenoic acid bioavailibility during heating
Change from baseline of plasma NO bioavailability 12 weeks Change in plasma nitrite bioavailibility during heating
Trial Locations
- Locations (2)
Department of Nephrology
🇫🇷Bois-Guillaume, France
Department of Pharmacology
🇫🇷Rouen, France