Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients with Alport Syndrome (COMBINE-ALPORT)

Launched by STEFAN LUJINSCHI · Jul 7, 2024

Keywords

ClinConnect Summary

The COMBINE-ALPORT trial is studying how effective two medications, Dapagliflozin and Spironolactone, are at lowering protein levels in the urine (albuminuria) of adults with Alport syndrome, a genetic kidney disorder that can lead to severe kidney damage. The goal is to see if taking these medications alone or together can help protect kidney function and delay the progression of the disease. This study is particularly important because there is limited information about treating a specific type of Alport syndrome that affects adults.

To participate in this trial, individuals must be between 18 and 70 years old and have a genetic diagnosis of Alport syndrome. They should have stable kidney function and specific levels of protein in their urine. Participants will be randomly assigned to receive one of the medications or a combination of both for four weeks at a time, with regular check-ins every month to monitor their health. This trial hopes to find new ways to better manage Alport syndrome and improve the quality of life for those affected.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• * Genetically proven Alport syndrome (AS) - defined as following:
• • gt;Men having hemizygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving men
• • gt;Women having heterozygous pathogenic/likely pathogenic variants involving COL4A5 gene - classified as X-linked AS involving women
• • gt;Both men and women with heterozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal dominant AS
• • gt;Both men and women with homozygous pathogenic/likely pathogenic variants involving COL4A3 or COL4A4 genes - classified as autosomal recessive AS
• • gt;Patients having variants of uncertain significance will be included if the fulfill at least 2 of the following criteria: (1) clinical features suggestive of AS, (2) positive family history suggestive of AS (i.e., at least one grade I relative having the same variant and presenting clinical features suggestive of AS) and (3) kidney biopsy showing the characteristic lesion of AS (i.e., structural defect of the glomerular basement membrane, "basket-wave" appearance of the basement membrane, lamination of the basement membrane) or for thin basement membrane disease (i.e., diffusely thin basement membrane)
• • Age between 18 and 70 years-old at the time of enrolment
• • Baseline estimated glomerular filtration rate (eGFR) over 10ml/min/1.73m2 at the time of enrolment
• • Stable kidney function: variation of eGFR under 25% from baseline in the last 6 weeks before randomization
• • 24-hours urine albumin-to-creatinine ratio greater than 30 mg/g after adjusting the dose of renin-angiotensin-system inhibitor
• • Stable renin-angiotensin-system inhibitor dose for at least 2 weeks before randomization
• Exclusion Criteria:
• • The need for kidney replacement therapy (i.e., hemodialysis, peritoneal dialysis, and kidney transplant) for more than 4 weeks in the last 12 months before enrollment
• • Treatment with Spironolactone or Dapagliflozin for more than 14 days in the last 28 days prior to enrollment
• • History of prior serious adverse event due to Spironolactone or Dapagliflozin
• • Active neoplasia
• • Autosomal dominant or recessive polycystic kidney disease
• • Type I diabetes
• • Patients with type II diabetes and diabetic nephropathy
• • Diagnosis of another concomitant distinct glomerulopathy (with the exception of concomitant IgA nephropathy on kidney biopsy)
• • Pregnancy and breastfeeding
• • History of solid organ transplant
• • Immunosuppressive treatment in the last 12 weeks prior to enrollment