STOP-PKD: SGLT2-inhibition to Improve Prognosis in Polycystic Kidney Disease

University of Cologne

Status and phase

Enrolling

Phase 3

Conditions

Polycystic Kidney, Autosomal Dominant

Treatments

Drug: Dapagliflozin 10 mg

Drug: Matching Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT07280585

2025-521276-59-00 (EU Trial (CTIS) Number)

Uni-Koeln-5522

Details and patient eligibility

About

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.

Full description

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.

Enrollment

420 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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
1. Truncating PKD1 mutation OR
2. eGFR loss > 3ml/min/year (determined by ≥ 4 creatinine values within 4 years, ≥ 6 months measurement intervals) OR
3. PROPKD score > 6 (patient history)
IF patient is on ACE-I /ARBs: stable dose for 4 weeks before screening

Exclusion criteria

Treatment with tolvaptan, somatostatin analogue, lithium or SGLT2i within the last 3 months before screening
Medical history of diabetic ketoacidosis, necrotizing fasciitis or organ transplantation
Diabetes mellitus type 1 or any type of diabetes mellitus due to insulin deficiency
Uncontrolled ongoing urinary tract or genital infections
Known intolerance of the study medication ingredients
Uncontrolled grade 2 hypertension (>160/100 mmHg)
Symptomatic hypotension, or systolic blood pressure <90 mmHg
Primary renal disease other than ADPKD
Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT]>3x the up-per limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
Pregnancy, breastfeeding or women of child-bearing potential not using effective contraception method
Not able to comply with the study protocol, in the investigator's judgement
Not able to provide informed consent
Participation in any other interventional clinical trial in the last 2 months