Chronic Kidney Diseases
Conditions
Keywords
Chronic Kidney Disease, Nephrology, eGFR
Brief summary
The proximal tubule remains the main site for sodium reabsorption in patients with advanced renal failure. The investigators therefore hypothesize that SGLT2i should still exert a significant natriuretic effect in patients with eGFR below 20 ml/min/1.73m2, and therefore should still decrease proteinuria with a potential renal protective effect.
Interventions
DRUGEmpagliflozin 10 MG then Placebo
Taking Empagliflozin first
DRUGPlacebo then Empagliflozin 10 MG
Taking the Empagliflozin in second
Sponsors
Centre Hospitalier Universitaire de Nice
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomized, double blind, placebo-controlled, cross over
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* type 2 diabetics, * age between 18 and 80 years, * RAS blockade at maximal tolerated dosage for 1 month, * eGFR (CKD-EPI) between 10 and 20 ml/min/1.73m2, * UACR \> 300mg/g creatinine and UPCR \> 500mg/g creatinine, * office systolic blood pressure \> 110 mmHg, * stable dosage of antihypertensive drugs and diuretics for 1 month. * for women of child-bearing age, an effective contraception (estroprogestative pill, contraceptive implant, IUD, condoms or tubal ligation) should be used for more than one month before the inclusion in the study. A urine pregnancy test (βHCG in urines) will be performed.
Exclusion criteria
* any medical condition that, in the opinion of the investigator makes the participant not suitable for inclusion, * history of ketoacidosis in the past while on empagliflozin or any other SGLT2i class drugs, * participation in another clinical study with an investigational medicinal product (IMP) administered during the month before screening, * known hypersensitivity or intolerance to empagliflozin or any of the excipients of the product, * judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements, * no social insurance, * unwilling to give informed consent, * vulnerable persons (minors, adults under guardianship or trusteeship, pregnant women, persons deprived of their liberty, persons unable to speak French).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-proteinuric effect | 20 months | Changes in mean UACR on spot morning urine samples between 2 days running at baseline and 2 days running at the end of each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, SGLT2i exerts a clinically significant anti-proteinuric effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body weight effect | 20 months | Changes in body weight between baseline and at the end of each 6-week treatment period (empagliflozin 10 mg/d and matching placebo. To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin acutely decreases body weight. |
| Urinary sodium effect | 20 months | To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin: increases urinary sodium excretion. Changes in mean UPCR on spot morning urine samples between 2 days running at baseline and 2 days running at the end of each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| Urinary volume effect | 20 months | To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin: increases urinary volume. Changes in mean 24-hour urinary. |
| Blood pressure effect | 20 months | To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin: decreases ambulatory blood pressure. Changes in mean ambulatory systolic blood pressure between 3 days running baseline and 3 days running at the end of each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| eGFR effect by good profile | 20 months | To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin has a good safety profile (no acute kidney injury or hyperkalaemia \> 5.5 mmol/L or acidosis (serum bicarbonate \<23 mmol/L)), |
| eGFR effect by levels | 20 months | Changes in eGFR levels between baseline and every week during each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| eGFR effect by serum potassium | 20 months | Changes in serum potassium levels between baseline and every week during each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| eGFR effect by serum bicarbonate | 20 months | Changes in serum bicarbonate levels between baseline and every week during each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| eGFR effect by albuminuria | 20 months | Changes in mean 24-hour albuminuria between 3 days running urinary collections at baseline and after starting each treatment period (empagliflozin 10 mg/d and matching placebo). |
| Effect on HbA1c | 20 months | To show that in type 2 diabetic patients with eGFR between 10 and 20 ml/min/1.73m2, empagliflozin has no significant effect on HbA1c. Changes in HbA1C between baseline and at the end of each 6-week treatment period (empagliflozin 10 mg/d and matching placebo). |
| Magnitude of eGFR by TEAEs | 20 months | Describe the magnitude of eGFR decrease following empagliflozin or placebo treatments with the description of treatment emergent adverse events (TEAEs). |
| Magnitude of eGFR by SAEs | 20 months | Describe the magnitude of eGFR decrease following empagliflozin or placebo treatments with the description of serious adverse events (SAEs). |
Countries
France
Contacts
CONTACTGuillaume FAVRE, MD-PHD
PRINCIPAL_INVESTIGATORGuillaume FAVRE, MD-PHD
Centre Hospitalier Universitaire de Nice
Outcome results
None listed