Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2025-521276-59-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| German Research Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
Autosomal dominant polycystic kidney disease is the most common genetic cause of kidney failure. The only approved treatment for ADPKD - tolvaptan - is limited in its use by massive therapy-associated polyuria. This trial tests if the SGLT2-inhibitor dapagliflozin slows down the loss of kidney function in ADPKD.
ADPKD is a genetic disease characterized by the growth of fluid-filled renal cysts, leading to progressive loss of kidney function. SGLT2- inhibitors have recently become available for the treatment of chronic kidney disease (CKD). The landmark trials, which proved the positive effect of SGLT2-inhibitors in CKD, excluded patients with ADPKD. Accordingly, current ADPKD-guidelines do not recommend the use of SGLT2-inhibitors in ADPKD.
This investigator-driven, randomized, placebo-controlled, multi-center, double-blind trial will assess the effect of daily dapagliflozin (10mg) intake on the chronic eGFR-slope in 420 patients with ADPKD. As a secondary endpoint the study will assess a composite endpoint triggered by reaching either 40%-eGFR loss, kidney failure or renal death. Safety aspects will additionally be addressed by an interim safety analysis considering total kidney volume, eGFR and copeptin-levels.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dapagliflozin 10 mg | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin 10 mg | Drug | Participants receive 10 mg of Dapagliflozin orally once daily for 36 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Chronic eGFR slope | The annual chronic eGFR slope will be calculated using all available serum creatinine values from week 6 to week 156 (end of treatment), using linear mixed models. | week 6 up to week 156 (end of treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in eGFR from pre-treatment to post-treatment (off-treatment values) | Change in kidney function will be assessed by comparing the mean eGFR values before treatment (calculated as the average of serum creatinine measurements at week -4 and week 0) with the mean eGFR values after treatment (calculated as the average of measurements at week 162 and week 168). The difference between these two timepoints represents the off-treatment change in kidney function. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in kidney function based on cystatin-C measurements | Annual slopes of eGFR decline (in mL/min/1,73m2 per year), as calculated with linear mixed models using all available cystatin-c values:
| week -4 until EOS (week 168) |
Inclusion Criteria:
Male and female patients with ADPKD (modified Ravine criteria) ≥ 18 and ≤ 60 years
Patients 18 - 39 years: eGFR ≥25 ml/min; patients 40 - 60 years: eGFR ≥25 and <90 ml/min/1.73 m2
Indicators of rapid progression, either of the following:
Mayo class 1D-E
Mayo class 1C AND EITHER
IF patient is on ACE-I /ARBs: stable dose for 4 weeks before screening
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Roman-Ulrich Müller, Prof. | Contact | +49221478191005 | STOP-PKD@uk-koeln.de | |
| Philipp Scherrer, MD | Contact | +49221478191005 | STOP-PKD@uk-koeln.de |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vorarlberger Krankenhaus-Betriebsgesellschaft | Not yet recruiting | Feldkirch | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40199734 | Background | Muller RU, Guerrot D, Chonchol M, Schmitt R, Uchiyama K, Gansevoort RT, Cornec-Le Gall E. SGLT2 inhibition for patients with ADPKD - closing the evidence gap. Nephrol Dial Transplant. 2025 Nov 26;40(12):2231-2238. doi: 10.1093/ndt/gfaf061. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Phase III, investigator-driven, multi-center, randomized, placebo-controlled, double-blind
Not provided
Not provided
Not provided
| Matching Placebo | Drug | Participants receive a matching placebo orally once daily for 36 months. |
|
| Week -4 to Week 168 |
| Time to first occurrence of a composite renal endpoint | Time from randomization to the first occurrence of any of the following events:
| From randomization (week 0) until end of follow-up (up to week 168) |
| Incidence of serious adverse events (SAEs) | All serious adverse events (SAEs) will be collected. | From randomization (week 0) until end of follow-up (week 168) |
| Incidence of adverse events of special interest (AESIs) | All adverse events of special interest (AESIs) will be collected. | From randomization (week 0) until end of follow-up (week 168) |
| Change in total kidney volume (TKV) after 1 year | In the first 150 enrolled participants, total kidney volume (TKV) will be measured at baseline and at week 48 using standardized MRI protocols. The change in TKV over 48 weeks will be used to assess potential effects of dapagliflozin on kidney size. | Baseline (week -4 until week 0) to week 48 (first 150 patients) |
| Changes in albuminuria | Worsening (increase >50% in comparison to baseline) or new onset of albuminuria (defined as >30mg albumin/g creatinine) | from randomization (week 0) until EOT (week 156) |
| Incidence of kidney stones | Number of symptomatic kidney stones (number of symptomatic episodes) | from randomization (week 0) until EOS (week 168) |
| Total eGFR slope | Total slope: annual slope of eGFR decline (in mL/min/1,73m2 per year), as calculated with linear mixed models, using all available creatinine values from baseline until end of treatment (week 0-156) | from randomization (week 0) until week 156 |
| Medizinische Universitaet Innsbruck | Recruiting | Innsbruck | Austria |
|
| Robert Bosch Gesellschaft für Medizinische Forschung mbH | Not yet recruiting | Stuttgart | Baden-Wurttemberg | 70376 | Germany |
|
| Klinikum Nürnberg | Not yet recruiting | Nuremberg | Bavaria | 90471 | Germany |
|
| Universitaetsklinikum Aachen AöR | Recruiting | Aachen | Germany |
|
| Charite Universitaetsmedizin Berlin KöR | Recruiting | Berlin | Germany |
|
| Universitätsklinikum Köln | Recruiting | Cologne | Germany |
|
| Klinikum Dortmund gGmbH | Recruiting | Dortmund | Germany |
|
| Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR | Recruiting | Dresden | Germany |
|
| Universitaetsklinikum Duesseldorf AöR | Not yet recruiting | Düsseldorf | Germany |
|
| Goethe University Frankfurt | Recruiting | Frankfurt | Germany |
|
| Medical Center - University of Freiburg | Not yet recruiting | Freiburg im Breisgau | 79106 | Germany |
|
| Universitaetsmedizin Goettingen | Not yet recruiting | Göttingen | Germany |
|
| University Medical Center Hamburg-Eppendorf | Not yet recruiting | Hamburg | Germany |
|
| Medizinische Hochschule Hannover | Recruiting | Hanover | Germany |
|
| Zentrum Fuer Nieren Hochdruck Und Stoffwechselerkrankungen | Not yet recruiting | Hanover | Germany |
|
| Universitaetsklinikum Heidelberg AöR | Not yet recruiting | Heidelberg | Germany |
|
| Universitaetsklinikum Jena KöR | Recruiting | Jena | Germany |
|
| Universitaetsklinikum Schleswig-Holstein AöR | Not yet recruiting | Kiel | Germany |
|
| Universitaet Leipzig | Recruiting | Leipzig | Germany |
|
| Universitaetsklinikum Schleswig-Holstein AöR | Recruiting | Lübeck | Germany |
|
| Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR | Recruiting | Mainz | Germany |
|
| Klinikum der Technischen Universitaet Muenchen | Not yet recruiting | München | Germany |
|
| LMU Klinikum Muenchen AöR | Recruiting | München | Germany |
|
| Klinikum Der Landeshauptstadt Stuttgart gKAöR | Recruiting | Stuttgart | Germany |
|
| Universitair Medisch Centrum Groningen | Recruiting | Groningen | Netherlands |
|
| Leids Universitair Medisch Centrum | Not yet recruiting | Leiden | Netherlands |
|
| Erasmus Universitair Medisch Centrum Rotterdam | Not yet recruiting | Rotterdam | Netherlands |
|
| Fundacio Hospital Universitari Vall D'Hebron Institut De Recerca | Not yet recruiting | Barcelona | Spain |
|
| Fundacio Puigvert | Not yet recruiting | Barcelona | Spain |
|
| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| D007690 | Polycystic Kidney Diseases |
| ID | Term |
|---|---|
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |
Not provided
Not provided
| ID | Term |
|---|---|
| C529054 | dapagliflozin |
Not provided
Not provided
Not provided