chronic kidney disease patients MedDRA version: 23.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Trade Name: FORXIGA
Pharmaceutical Form: Tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharm
Sponsors
CHU de Rouen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. - Chronic kidney disease (eGFR = 25 and = 60 mL/min/1.73m² by CKD-EPI) 2. - Age = 18 years 3. - 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). 4. Patient having read and understood the information letter and signed the Informed Consent Form 5. 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. 6. Patient able to comply with the study protocol, in the investigator’s judgment 7. Patient affiliated with, or beneficiary of a social security (health insurance) category. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Type 1 and type 2 diabetes (fasting glycemia = 126 mg/dL or use of oral hypoglycemic agents or insulin) 2. Recessive or autosomal dominant polycystic kidney disease 3. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis 4. Lupus nephritis 5. Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment 6. History of organ transplantation 7. Body weight > 35 kg/m² 8. Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor 9. Receiving phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil or other) or riociguat (due to the risk of hypotension potentiation with GTN spray). 10. Patients with NYHA class IV congestive heart failure at the time of enrolment 11. Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment 12. 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 13. Active malignancy requiring treatment at the time of enrolment or is planned to undergo any treatment after randomization 14. Severe hepatic impairment (Child-Pugh class C) 15. History of frequent genital mycotic infections (> 2 during the last 12 months) 16. Current pregnancy OR women who are breast-feeding 17. 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 18. - Contra-indication to FORXIGA 10 mg film-coated tablets: hypersensitivity to dapagliflozin or to any of the excipients 19. - Participation in another clinical study with an investigational product during the last 4 weeks prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that 12-week treatment with dapagliflozin improves endothelium-dependent flow-mediated dilatation of peripheral conduit arteries during short-term increase in blood flow in chronic kidney disease patients;Secondary Objective: To demonstrate that 12-week treatment with dapagliflozin improves endothelium-dependent flow-mediated dilatation of peripheral conduit arteries during sustained increase in blood flow in chronic kidney disease patients - To demonstrate that 12-week treatment with dapagliflozin improves the bioavailability of endothelial vasodilating factors in chronic kidney disease patients - To demonstrate that 12-week treatment with dapagliflozin reduces oxidative stress and inflammation in chronic kidney disease patients - To demonstrate that 12-week treatment with dapagliflozin improves arterial stiffness and cardiovascular coupling in chronic kidney disease patients - To demonstrate that 12-week treatment with dapagliflozin improves cardiac function in chronic kidney disease patients ;Primary end point(s): Change in the magnitude of brachial artery flow-mediated dilatation in response to reactive hyperemia after 12-week treatment with dapagliflozin or placebo;Timepoint(s) of evaluation of this end point: 84 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in the magnitude of radial artery flow-mediated dilatation in response to hand skin heating after 12-week treatment with dapagliflozin or placebo - Change in the plasma release of nitric oxide and epoxyeicosatrienoic acids induced by hand skin heating after 12-week treatment with dapagliflozin or placebo - Change in the plasma levels of pro-oxidant and pro-inflammatory lipid mediators 12-week treatment with dapagliflozin or placebo - Change in carotid artery elastic modulus, carotid-to-femoral pulse wave velocity and aortic augmentation index after 12-week treatment with dapagliflozin or placebo - Change in cardiac output, stroke volume, ejection fraction and left ventricular end-systolic elastance after 12-week treatment with dapagliflozin or placebo ;Timepoint(s) of evaluation of this end point: 84 days | — |
Countries
France
Contacts
Public ContactBlot Julien
CHU de Rouen
Outcome results
None listed