Abstract: INFO13-FR
Pediatric and Young Adult Populations with CKD: Protocol and Rationale for the Randomized Controlled SGLT2 Inhibitor Trial DOUBLE PRO-TECT Alport
Session Information
- Informational Posters - 2
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- No subcategory defined
Authors
- Gross, Oliver, Universitatsmedizin Gottingen, Gottingen, Niedersachsen, Germany
- Boeckhaus, Jan, Universitatsmedizin Gottingen, Gottingen, Niedersachsen, Germany
Group or Team Name
- For the DOUBLE PRO-TECT Alport Investigators and the Study Group of the German Society of Pediatric Nephrology.
Description
Background and hypothesis. Clinical trials have demonstrated positive cardiovascular and kidney outcomes of sodium-glucose-co-transporter-2 (SGLT2) inhibitors in elderly adult patients with diabetic and other chronic kidney diseases (CKD). Whether benefits extend to children, teenagers, and young adults with early-stage CKD is unknown. For this reason, the DOUBLE PRO-TECT Alport trial (NCT05944016, EU TrialNo. 2023-508502-18-00) will study the progression of albuminuria in young patients with Alport syndrome to assess the safety and efficacy of the SGLT2-inhibitor dapagliflozin.
Methods and Rationale. DOUBLE PRO-TECT Alport is a multicenter, randomized, double-blind, placebo-controlled trial (RCT), funded by the German Research Foundation. Participants (aged 10 to 39 years) must have a diagnosis of AS and must have a Urinary Albumin to Creatinine Ratio (UACR) of >300 mg/g and estimated glomerular filtration rate (eGFR) >30 ml/min (pediatric) or UACR >500 mg/g and eGFR >60 ml/min (adult).
The trial protocol has been approved by the European authorities, trial sites have been initiated and started recruiting. The first participants have been randomized at a 2:1 ratio to 48 weeks of treatment with dapaglifozin 10 mg/day -to- matched placebo. In addition to safety, the primary (change in UACR from baseline to Week 48) and key secondary (eGFR change from baseline to Week 52) efficacy outcomes will be analyzed with a mixed model repeated measures approach. Efficacy analyses will be performed primarily in the full analysis set according to the intention-to-treat principle. A sensitivity analysis will be performed using reference-based multiple imputation.
Conclusion. The population of children with CKD has been excluded so far from clinical development of SGLT2-inhibitors. This trial will close this knowledge gap. DOUBLE PRO-TECT Alport will assess whether SGLT2-inhibitors can safely reduce change from baseline in UACR as a marker for progression of CKD in young patients.
Funding
- German Research Foundation (DFG).