C3 glomerulopathy
Conditions
Interventions
Trade Name: aliskiren generic
rasilez trade name
Pharmaceutical Form: Tablet
Trade Name: enalapril generic
Product Name: enalapril
Pharmaceutical Form: Tablet
Sponsors
Skåne University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children = 6 years and adults. 2. Initial diagnosis of Dense Deposit Disease and C3 glomerulonephritis confirmed by kidney biopsy obtained not more than 2 years before the first dose of the study drug. 3. Either absence of treatment at the study start or ongoing treatment with aliskiren, ACEi, ARBs or immune suppressive medications (such as mycophenolate mofetil/MMF or corticosteroids) 4. Written informed consent has been given by: a. the patient’s legal guardians if the patient is less than 15 years old b. the patient and his/her legal guardians if the patient is = 15 but =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Known allergy to aliskiren or enalapril or substances contained in these preparations. 2. Angioedema caused by aliskiren or enalapril 3. Weight < 25 kg. 4. Glomerular filtration rate = 50 ml/min/1.73 m2 (measured by iohexol clearance) in children and = 30 ml/min/1.73 m2 in adults. 5. Rapid deterioration of kidney function during the latest year of the disease 5. Patients with a renal transplant. 6. Immune complex-mediated membranoproliferative glomerulonephritis (such as in HIV infection, hepatitis, SLE). 7. Females who breastfeed, are pregnant or planning to become pregnant during the study. 8. Co-morbidity such as malignancy, congestive heart failure, recent myocardial infarction. 9. Mental incapacity or language barriers to understand the contents of the study design. 10. Simultaneous use of another complement-antagonist (such as eculizumab). Eculizumab must be discontinued and complement activity normalized before the start of study drug. 11. Simultaneous use of aliskiren or enalapril with cyclosporine or nonsteroidal anti-inflammatory drugs (NSAID).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this project is to assess aliskiren, a direct renin inhibitor, as a novel treatment to block complement activation in the kidneys and thereby attenuate renal disease and stabilize or improve kidney function and compare it to the currently used treatment with an angiotensin converting enzyme inhibitor (ACEi) in patients with the complement-mediated renal disease C3 glomerulopathy. The primary objective is to assess the effect and safety of aliskiren on reducing systemic and local complement activation as indicated by a reduction of serum C3 during a cross-over study and serum C3 and complement deposition in renal biopsies during an extension study in patients with C3 glomerulopathy as compared to the currently used treatment with enalapril (ACEi). ;Secondary Objective: To assess the effect of aliskiren as compared to the currently used treatment with ACEi enalapril on: complement activation (such as serum C3a, C3d, C5a and related complement assays), proteinuria, kidney function, kidney biopsy findings, blood pressure, activation of the renin angiotensin system. ;Primary end point(s): The primary end-point assays include: Blood samples related to complement activation: C3. Renal biopsies: complement deposition.;Timepoint(s) of evaluation of this end point: Start and every 3rd month for 3 years: C3 in blood samples. Kidney biopsy: within 2 years of start and within 3 years of the start of the trial or at the end. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blood samples related to complement activation: C3d, C3a, C5a, C5, TCC, C3 nephritic factor and related complement assays. Albumin level. Urine samples: urine dipstick, albumin/creatinine ratio, angiotensinogen Kidney function with iohexol clearance Kidney biopsy: within 2 years of start and within the 3 years of the trial or at the end. ;Timepoint(s) of evaluation of this end point: Blood samples: C3d, C3a, C5a, albumin, creatinine at start and every third month. Urine samples: urine dipstick, albumin/creatinine ratio, angiotensinogen at start and every third month. After 6, 12, 24 and 36 months also C5, properdin, soluble terminal complement complex, C3 nephritic factor, related complement assays. Start and every 12 months: kidney function with iohexol clearance Kidney biopsy: within 2 years of start and within the 3 years of the trial or at the end. | — |
Countries
Sweden
Contacts
Public ContactDepartment of Pediatrics
Skåne University Hospital
Outcome results
None listed