Impact of Dapagliflozin on Vascular Function in Chronic Kidney Disease Patients
Overview
- Phase
- Phase 2
- Intervention
- Dapagliflozin 10Mg Tab
- Conditions
- Renal Insufficiency, Chronic
- Sponsor
- University Hospital, Rouen
- Enrollment
- 32
- Locations
- 2
- Primary Endpoint
- Change from baseline of brachial artery endothelial function using echography
- Status
- Completed
- Last Updated
- 2 months ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Dapagliflozin 10Mg Tab
Dapagliflozin 10 mg film-coated tablets
Intervention: Dapagliflozin 10Mg Tab
Dapagliflozin 10Mg Tab
Dapagliflozin 10 mg film-coated tablets
Intervention: impedance cardiography
Dapagliflozin 10Mg Tab
Dapagliflozin 10 mg film-coated tablets
Intervention: Applanation tonometry
Dapagliflozin 10Mg Tab
Dapagliflozin 10 mg film-coated tablets
Intervention: post-ischemic hyperemia of forearm
Dapagliflozin 10Mg Tab
Dapagliflozin 10 mg film-coated tablets
Intervention: haemodynamics parameters
Placebo
Identical film-coated tablets without dapagliflozin
Intervention: Placebo
Placebo
Identical film-coated tablets without dapagliflozin
Intervention: impedance cardiography
Placebo
Identical film-coated tablets without dapagliflozin
Intervention: Applanation tonometry
Placebo
Identical film-coated tablets without dapagliflozin
Intervention: post-ischemic hyperemia of forearm
Placebo
Identical film-coated tablets without dapagliflozin
Intervention: haemodynamics parameters
Outcomes
Primary Outcomes
Change from baseline of brachial artery endothelial function using echography
Time Frame: 12 weeks
Change in brachial artery flow-mediated dilatation in response to post-ischemia hyperemia using difference of brachial artery diameter
Secondary Outcomes
- Change from baseline of arterial stiffness using applanation tonometry(12 weeks)
- Change from baseline of carotid artery geometry using echography (2)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (2)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (6)(12 weeks)
- Change from baseline of carotid artery geometry using echography (1)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (1)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (3)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (4)(12 weeks)
- Change from baseline of cardiac function by impedance cardiography (5)(12 weeks)
- Change from baseline of epoxyeicosatrienoic acid bioavailability(12 weeks)
- Change from baseline of plasma NO bioavailability(12 weeks)