Evaluation of a Renin Inhibitor, Aliskiren, Compared to Enalapril, in C3 Glomerulopathy
C3 Glomerulopathy, Membranoproliferative Glomerulonephritis, Complement Abnormality
About this trial
This is an interventional treatment trial for C3 Glomerulopathy
Eligibility Criteria
Inclusion Criteria:
- Children ≥ 6 years and adults.
- 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.
- Either absence of treatment at the study start or ongoing treatment with aliskiren, angiotensin converting enzyme inhibitors, angiotensin receptor blockers or immune suppressive medications (such as mycophenolate mofetil/MMF or corticosteroids)
Written informed consent has been given by:
- the patient's legal guardians if the patient is less than 15 years old
- the patient and his/her legal guardians if the patient is ≥ 15 but < 18 years old
- the patient, if the patient is ≥ 18 years old
Female subjects of childbearing potential must:
- Understand that the study medication is expected to have a teratogenic risk
Agree to use a highly effective contraceptive during study drug therapy. This applies unless the subject is less than 18 years of age, has not had sexual debut and commits to sexual abstinence confirmed by a pregnancy test on every study visit. Either of the following methods of contraception may be used:
- Combined (estrogen and progesterone) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence
- Male or female condom with or without spermicide
- Cap, diaphragm or sponge with spermicide
- Agree to have a pregnancy test before the start of study medication. This requirement also applies to women of childbearing age who practice complete and continued abstinence and adolescent girls after menarche.
- Agree to have a pregnancy test every 3rd month including at the end of study treatment, except in the case of confirmed tubal sterilization. This requirement also applies to women of childbearing age who practice complete and continued abstinence and adolescent girls after menarche.
Exclusion Criteria:
- Known allergy to aliskiren, ACEi or substances contained in these preparations.
- Angioedema caused by aliskiren or enalapril
- Weight < 25 kg
- Glomerular filtration rate ≤ 50 ml/min/1.73 m2 (measured by iohexol clearance) in children and ≤ 30 ml/min/1.73 m2 in adults.
- Rapid deterioration of kidney function during the latest year of the disease
- Patients with a renal transplant
- Immune complex-mediated membranoproliferative glomerulonephritis (such as in HIV infection, hepatitis, SLE)
- Females who breastfeed, are pregnant or planning to become pregnant during the study.
- Co-morbidity such as malignancy, congestive heart failure, recent myocardial infarction.
- Mental incapacity or language barriers to understand the contents of the study design.
- Simultaneous use of another complement-antagonist (such as eculizumab). Eculizumab must be discontinued and complement activity normalized before the start of study drug.
- Simultaneous use of aliskiren or enalapril with cyclosporine or nonsteroidal anti-inflammatory drugs (NSAID).
Sites / Locations
- Sahlgrenska Hospital
- Region Skåne Skåne UniversitetssjukhusRecruiting
- Karolinska Hospital
- Akademiska sjukhuset
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Aliskiren treatment
Enalapril treatment
Patients will be randomized to tablet treatment with aliskiren (target daily dose) 150-300 mg once daily or every other day (depending on weight) for 6 months. After 6 months the patients will be switched to tablet treatment with enalapril (target daily dose 7.5-20 mg once or twice a day) for the coming 2,5 years.
Patients will be randomized to tablet treatment with enalapril (target daily dose 7.5-20 mg once or twice a day) for 6 months. After 6 months the patients will be switched to tablet treatment with aliskiren (target daily dose) 150-300 mg once daily or every other day (depending on weight) for the coming 2,5 years.