Protocol and rationale for a randomized controlled SGLT2 inhibitor trial in paediatric and young adult populations with chronic kidney disease: DOUBLE PRO-TECT Alport.

Abstract

Background: Clinical trials have demonstrated positive cardiovascular and kidney outcomes of sodium-glucose co-transporter 2 (SGLT2) inhibitors in adult patients with diabetic and other chronic kidney diseases (CKDs). 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) will study the progression of albuminuria in young patients with Alport syndrome (AS), the most common hereditary CKD, to assess the safety and efficacy of the SGLT2 inhibitor dapagliflozin. Patients living with AS and chronically elevated albuminuria have a high risk of kidney failure before the age of 50 years.

Methods: DOUBLE PRO-TECT Alport is a multicentre, randomized, double-blind, placebo-controlled trial. Participants (ages 10-39 years) must have a diagnosis of AS by genetic testing or kidney biopsy, be on a stable (>3 months) maximum tolerated dose of a renin-angiotensin system inhibitor and have a urinary albumin:creatinine ratio (UACR) of >300 mg/g (paediatric) or >500 mg/g (adult).Eligible participants will be randomly assigned at a 2:1 ratio to 48 weeks of treatment with dapaglifozin 10 mg/day or matched placebo. Most participants are expected to be children with a normal estimated glomerular filtration rate (eGFR). 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 analysed 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: DOUBLE PRO-TECT Alport will assess whether SGLT2 inhibitors can safely reduce the UACR change from baseline as a marker for progression of CKD in young patients living with AS.