Vascular Impact of Dapagliflozin in CKD Patients (DAPAVASC)

Renal Insufficiency, Chronic Clinical Trial

— DAPAVASC  

Official title:

Impact of Dapagliflozin on Vascular Function in Chronic Kidney Disease Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04930549
• Other study ID #: 2021/0188/HP
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: October 2021
• Source: University Hospital, Rouen
• Contact: Julien Blot
• Phone: +33232884035
• Email: julien.blot[@]chu-rouen.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 54
• Est. completion date: March 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• 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.

Related Conditions & MeSH terms

• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Dapagliflozin 10Mg Tab
Patients receive dapagliflozin 10mg tablets once a day during 12 weeks
• Placebo
Patients receive placebo tablets once a day during 12 weeks

Procedure:
• impedance cardiography
impedance cardiography (PhysioFlow® PF-05 Lab1TM, Manatec Biomedical) is done for evaluation of cardiac function
• Applanation tonometry
Applanation tonometry will be done using SphygmoCor®, Hogimed) is done for evaluation of arterial stiffness
• post-ischemic hyperemia of forearm
An arterial occlusion cuff will be placed on the forearm, and will be deflated to allow post-ischemic hyperemia with the continuous measurements of brachial artery diameter and blood flow velocity by high-resolution echotracking coupled to a Doppler system (ArtLab system®)
• haemodynamics parameters
haemodynamics parameters will be evaluated using automatic oscillometric recorder

Locations

Country	Name	City	State
France	Department of Nephrology	Bois-Guillaume
France	Department of Pharmacology	Rouen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Rouen	AstraZeneca

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of brachial artery endothelial function using echography	Change in brachial artery flow-mediated dilatation in response to post-ischemia hyperemia using difference of brachial artery diameter	12 weeks
Secondary	Change from baseline of arterial stiffness using applanation tonometry	Change in carotid-to-femoral pulse wave velocity	12 weeks
Secondary	Change from baseline of carotid artery geometry using echography (1)	Change in carotid diastolic diameter	12 weeks
Secondary	Change from baseline of carotid artery geometry using echography (2)	Change in carotid intima-media thickness using echography	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (1)	Change in cardiac output	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (2)	Change in stroke volume	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (3)	Change in ejection fraction	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (4)	Change in end-diastolic volume	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (5)	Change in total peripheral resistance,	12 weeks
Secondary	Change from baseline of cardiac function by impedance cardiography (6)	Change in left ventricular end-systolic elastance	12 weeks
Secondary	Change from baseline of epoxyeicosatrienoic acid bioavailability	Change in epoxyeicosatroenoic acid bioavailibility during heating	12 weeks
Secondary	Change from baseline of plasma NO bioavailability	Change in plasma nitrite bioavailibility during heating	12 weeks