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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dapagliflozin 10 mg
  Participants receive 10 mg of Dapagliflozin orally once daily for 36 months.
• Препарат Matching Placebo
  Participants receive a matching placebo orally once daily for 36 months.

Первичные конечные точки

• Chronic eGFR slope [Срок оценки: week 6 up to week 156 (end of treatment)]

Вторичные конечные точки (5)

• Change in eGFR from pre-treatment to post-treatment (off-treatment values) [Срок оценки: Week -4 to Week 168]
• Time to first occurrence of a composite renal endpoint [Срок оценки: From randomization (week 0) until end of follow-up (up to week 168)]
• Incidence of serious adverse events (SAEs) [Срок оценки: From randomization (week 0) until end of follow-up (week 168)]
• Incidence of adverse events of special interest (AESIs) [Срок оценки: From randomization (week 0) until end of follow-up (week 168)]
• Change in total kidney volume (TKV) after 1 year [Срок оценки: Baseline (week -4 until week 0) to week 48 (first 150 patients)]

Критерии участия

Критерии включения

• 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

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Германия · 23 центра

• Robert Bosch Gesellschaft für Medizinische Forschung mbH — Stuttgart
• Klinikum Nürnberg — Nuremberg
• Universitaetsklinikum Aachen AöR — Aachen
• Charite Universitaetsmedizin Berlin KöR — Berlin
• Universitätsklinikum Köln — Cologne
• Klinikum Dortmund gGmbH — Dortmund
• Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden Aö — Dresden
• Universitaetsklinikum Duesseldorf AöR — Düsseldorf
• … и ещё 15 центров

Нидерланды · 3 центра

• Universitair Medisch Centrum Groningen — Groningen
• Leids Universitair Medisch Centrum — Leiden
• Erasmus Universitair Medisch Centrum Rotterdam — Rotterdam

Австрия · 2 центра

• Vorarlberger Krankenhaus-Betriebsgesellschaft — Feldkirch
• Medizinische Universitaet Innsbruck — Innsbruck

Испания · 2 центра

• Fundacio Hospital Universitari Vall D'Hebron Institut De Recerca — Barcelona
• Fundacio Puigvert — Barcelona

Публикации

• 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. PMID 40199734

Идентификаторы

NCT: NCT07280585 · Uni-Koeln-5522 · 2025-521276-59-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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