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Kidney Week

Abstract: INFO11-TH

DOUBLE PRO-TECT Alport: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Effect of Dapagliflozin on the Progression of Kidney Disease in Young Patients with Alport Syndrome

Session Information

  • Informational Posters - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • No subcategory defined

Authors

  • Gross, Oliver, Georg-August-Universitat Gottingen Medizinische Fakultat, Goettingen, Niedersachsen, Germany
  • Boeckhaus, Jan, Georg-August-Universitat Gottingen Medizinische Fakultat, Goettingen, Niedersachsen, Germany

Group or Team Name

  • for the DOUBLE PRO-TECT Alport steering committee
Description

Alport syndrome (AS) is a common genetic cause of end-stage kidney failure (ESKF) and is responsible for about 3% cases of chronic kidney disease (CKD) in adults. Most untreated children with AS reach ESKF before 25 years of age, resulting in an impaired quality of life and reduced life-expectancy. Angiotensin-converting enzyme inhibitors (ACEi) slow CKD-progression in AS. However, despite ACEi, all patients still progress early in life. Recent trials have demonstrated positive renal outcomes of sodium–glucose co-transporter-2 inhibitors (SGLT2i) additive to ACEis in adult patients with diabetic and non-diabetic CKD. These trials included less than 10 adult AS patients and no children.
Here we report the trial outline about the worldwide first pediatric CKD randomized controlled trial with SGLT2i. Our hypothesis is to demonstrate superiority of the SGLT2i dapagliflozin in preventing progression of AS in children and young adults at early stages of disease. Key inclusion criteria are (1) Early stages of CKD with established diagnosis of AS at screening visit; (2) adolescents ≥ 10 to < 18 years with albuminuria (UACR ≥ 300mg/g creatinine) OR adults ≥ 18 to < 40 years with albuminuria (UACR ≥ 500mg/g creatinine) AND eGFR ≥ 60 ml/min/1.73 m2; (3) Stable RAS blockade as background therapy. After 2:1 randomization Dapagliflozin:Placebo, 102 patients will be treated with 10 mg p.o. once daily for 48 weeks plus 4 weeks of safety follow-up. Primary endpoint will be change from baseline UACR after 48 weeks; key secondary endpoint will be change from baseline eGFR after 52 weeks. Safety will be assessed including adverse events of special interest: (a) Ketoacidosis or hypoglycemic event; (b) Hyperkalemia; (c) Decline in eGFR of ≥ 30% relative from baseline eGFR. First patient in is expected 12/2023. The trial is sponsored by a research grant of the German Research Foundation to O.G. (DFG GR 1852/7-1) and is not supported by industry.

Funding

  • Funded by a research grant of the German Research Foundation to O. Gross (DFG GR 1852/7-1).