Autosomal Dominant Polycystic Kidney
Conditions
Brief summary
The EMPA-PKD trial is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use by monitoring kidney growth and the rate of loss of kidney function.
Detailed description
In autosomal dominant polycystic kidney disease (ADPKD) formation of cysts in the kidneys causes destruction of functional parenchyma and loss of kidney function, which may progress to end-stage kidney disease. Tolvaptan is the only drug specifically approved for slowing down the progression of ADPKD. Sodium glucose cotransporter 2 inhibitors (SGLT2i) might provide additional benefits but there is currently no information on safety and outcome effects of SGLT2i in patients with ADPKD, as these patients were excluded in the landmark SGLT2i trials. In an investigator-initiated, double-blind, mono-center, placebo-controlled, randomized clinical trial the EMPA-PKD study is assessing the safety of empagliflozin in patients with rapid progressive ADPKD with and without concomitant tolvaptan use by monitoring kidney growth and the rate of loss of kidney function. 44 participants will be randomly allocated (1:1) to receive a daily dose of either empagliflozin (10 mg/day) or placebo for 18 months. Patients will be stratified according to concomitant tolvaptan use. The primary endpoint is progression of cystic kidney growth by monitoring MRI-based changes in total kidney volume and the secondary endpoint is exploring changes in glomerular filtration rate. Additional endpoints include adverse events and changes in copeptin levels, albuminuria and blood pressure.
Interventions
DRUGEmpagliflozin 10 MG
Oral
DRUGPlacebo
Oral
Sponsors
Boehringer Ingelheim
Hannover Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female\* patients ≥ 18 of age 2. Screening eGFR ≥ 25 and ≤ 90 mL/min/1.73 m2 if age ≥ 18 and ≤50 years or Screening eGFR ≥ 25 and ≤ 65 mL/min/1.73 m2 if age \> 50 years 3. ADPKD diagnosed by unified criteria (combination of family history, ultrasound, MRI/CT, genotyping as needed) 4. Mayo Class I C, D, E 5. Patients with and without tolvaptan use will be included. Patients with tolvaptan use will be included if tolvaptan has been taken for ≥ 3 months at study entry. 6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures 7. Evidence of signed written informed consent.
Exclusion criteria
1. Kidney or any other solid organ transplant recipient 2. Currently receiving SGLT2-inhibitor 3. Concomitant treatment with steroids or any other immunosuppressive agent 4. Hypersensitivity to the active principle (Empagliflozin) or any of the excipients (e.g. lactose) 5. Ketoacidosis (laboratory based) in the past 5 years 6. Type 1 diabetes mellitus 7. Ongoing urinary tract- or genital infections 8. Inability to fully understand the possible risks and benefits related to study participation 9. Inability to undergo MRI exam (e.g. implanted medical devices) 10. Women who are pregnant or breastfeeding 11. Unwilling to practice acceptable methods of birth control during study participation 12. Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total kidney volume (TKV) | 18 months | Relative change from baseline TKV (percent/year) to month 18 of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated glomerular filtration rate (eGFR) | 18 months | Change in the eGFR from baseline to month 18 of treatment |
Countries
Germany
Outcome results
None listed