Impact of dapagliflozin on vascular function in chronic kidney disease patients - (DAPA-VASC)

Prior treatment

• Receiving phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil or other) or riociguat (due to the risk of hypotension potentiation with GTN spray).
• 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
• Participation in another clinical study with an investigational product during the last 4 weeks prior to enrolment
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment

Other illness

• Patients with NYHA class IV congestive heart failure at the time of enrolment
• 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 pancreatitis
• History of frequent genital mycotic infections (> 2 during the last 12 months)
• Patients whose conditions lead to reduced food absorption or severe dehydration
• Contraindications to NATISPRAY® 0.30mg/dose, solution for oral spray : - Hypersensitivity to nitrates or to any of the excipients, - State of shock, severe hypotension, - In combination with sildenafil, taladafil, vardenafil, avanafil and riociguat - Obstructive cardiomyopathy, - Inferior site myocardial infarction with extension to the right ventricle, acute phase, except when there is a sign of left ventricular failure, - Intracranial hypertension
• Contra-indication to FORXIGA 10 mg film-coated tablets: hypersensitivity to dapagliflozin or to any of the excipients
• Patients with increased insulin requirements due to an acute medical condition, surgery or excessive alcohol consumption
• Recessive or autosomal dominant polycystic kidney disease
• History of organ transplantation

Lab values

• Type 1 and type 2 diabetes (fasting glycemia ≥ 126 mg/dL or use of oral hypoglycemic agents or insulin)
• Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Other

• Body weight > 35 kg/m²
• Current pregnancy OR women who are breast-feeding
• Patients with reduced insulin levels
• Lupus nephritis

• 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 unable to take angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
• Patient having read and understood the information letter and signed the Informed Consent Form
• For women: a. Women of childbearing potential : i. Effective contraception according to CTFG contraception recommendations (V1.1 21/09/2020) since at least 4 weeks before randomization and during treatment, and; ii. Negative blood pregnancy test; b. Women surgically sterile (absence of ovaries and/or uterus); c. Postmenopausal women (non-medically induced amenorrhea for at least 12 months prior to the inclusion visit). Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Barrier methods must always be supplemented with the use of a spermicide.
• Patient able to comply with the study protocol, in the investigator's judgment
• Patient affiliated with, or beneficiary of a social security (health insurance) category.