Chronic Kidney Failure in Children and Young Adults
Conditions
Keywords
chronic kidney disease in children, pediatric population, nephroprotective therapy in children, Alport syndrome, type IV collagen disease
Brief summary
Recent trials have demonstrated positive renal outcomes of sodium-glucose co-transporter-2 inhibitors (SGLT2i) additive to angiotensin-converting-enzyme inhibitors (ACEis) in adult patients with diabetic and non-diabetic chronic kidney disease (CKD). These trials included no children. The hypothesis of DOUBLE PRO-TECT Alport is to demonstrate superiority of the SGLT2i dapagliflozin in preventing progression of the chronic kidney disease Alport syndrome in children and young adults at early stages of disease. Preventing the rise of albuminuria by dapagliflozin would result in a very significant delay of end-stage kidney failure (ESKF) and improved quality of life. If successful, DOUBLE PRO-TECT Alport will change the treatment recommendations for children with CKD, who have a very high unmet medical need.
Interventions
DRUGDapagliflozin
Dapagliflozin (standard dose 10 mg p.o. once daily)
DRUGPlacebo
Placebo (standard dose p.o. once daily)
Sponsors
German Research Foundation
University Hospital Goettingen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-blinded study using capsules.
Intervention model description
Experimental intervention: Dapagliflozin (standard dose 10 mg p.o. once daily). Control intervention: Placebo therapy.
Eligibility
Sex/Gender
ALL
Age
10 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: Early stages of CKD with established diagnosis of Alport syndrome at visit 1 (screening) * adolescents ≥ 10 to \< 18 years with albuminuria (UACR ≥ 300mg/g creatinine) AND * eGFR ≥ 30 ml/min/1.73 m2 OR * adults ≥ 18 to \< 40 years with albuminuria (UACR ≥ 500mg/g creatinine) AND * eGFR ≥ 60 ml/min/1.73 m2 1. Molecular-genetic diagnosis or diagnosis established by kidney biopsy 2. Stable RAS blockade as background therapy. 3. Signed and dated written informed consent. Key
Exclusion criteria
1. Medical history that might limit the individual's ability to take trial treatments. 2. Treatment with any SGLT2 inhibitor or within 4 weeks prior to Visit 1. 3. eGFR\<60 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis or after kidney-transplantation 4. Uncontrolled arterial hypertension (blood pressure above 145/95 mmHg). 5. Known hypersensitivity or allergy to the investigational products. 6. Any previous or current alcohol or drug abuse. 7. Participation in another trial with an investigational drug ongoing. 8. Women, who are nursing or pregnant, or who are not practicing an acceptable method of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary endpoint | 48 weeks | Change from baseline urine albumin to creatinine ratio (UACR) after 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key secondary efficacy endpoint | 52 weeks | Change from baseline estimated glomerular filtration rate (eGFR) after 52 weeks (4 weeks off treatment) |
| Key secondary safety endpoint | 52 weeks | Adverse events (including serious adverse events) |
| Adverse events (AE) of special interest | 52 weeks | (a) Ketoacidosis or symptomatic hypoglycemic event. |
Countries
Germany
Contacts
Primary ContactOliver Gross, MD
Outcome results
None listed