Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

Study Overview
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Brief Summary
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Evaluation of the efficacy of an immunosuppressive therapy added to a comprehensive supportive therapy to induce a clinical remission in patients at risk for progressive IgAN Investigation of differences between the treatments regarding the number of patients loosing more than 15 ml/min of GFR.

Detailed Description
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The best treatment of glomerular diseases of the kidney is currently not well defined. This study aims to answer if in patients with IgA nephropathy, the most common type of glomerulonephritis an immunosuppressive treatment (with the use of steroids and chemotherapy) added to a supportive treatment is more effective than a supportive treatment alone (with the use of drugs lowering the blood pressure and the urinary protein loss).

Official Title
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Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: supportive therapy with: ACE-inhibitor / ARB / Statin
* Drug: supportive and immunosuppressive therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients from 18-70 years with histologically proven primary IgAN with typical mesangioproliferative features. Diagnosis has to be made by a neuropathologist. Proteinuria above 0.75 g/day within 12 weeks prior to or at the first visit in the run-in phase (month -6)and presence of at least one further risk factor for the development of end stage renal disease arterial hypertension, defined as ambulatory blood pressure >140/90 mm Hg or the use of antihypertensive medication or impaired renal function, defined as creatinine clearance or estimated GFR <90 ml/min. Exclusion Criteria: Known allergy or intolerance to study medication (except in case of ACE-inhibitor, in which case a change to an angiotensin receptor blocker is possible). Women who are pregnant or breastfeeding and women without sufficient contraception. Any prior immunosuppressive therapy. Variants of primary IgAN (e.g. rapidly progressive IgAN with crescents in >50% of glomeruli or minimal change GN with glomerular IgA deposits). Significant liver dysfunction (more than three fold increased GPT compared to norm) Contraindication for immunosuppressive therapy, like acute or chronic infectious disease incl. hepatitis and HIV positive patients any malignancy leukocytopenia, thrombocytopenia or known allergy against prednisolone, cyclophosphamide or azathioprine active intestinal bleeding, active gastric or duodenal ulcer Need of permanent immunosuppression, (e.g. transplanted patients, steroid-dependent inflammatory diseases) Secondary IgAN or diseases associated with glomerular deposits of IgA. Additional other chronic renal disease. Creatinine clearance below 30 ml/min (mean of 3 measurements). Alcohol or drug abuse Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study Participation in a parallel clinical trial or participation in another clinical trial within the last 3 months. Subjects who are in any state of dependency to the sponsor or the investigators. Employees of the sponsor or the investigators. Subjects who have been committed to an institution by legal or regulatory order.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: supportive therapy with: ACE-inhibitor / ARB / Statin<br>* Antihypertensive therapy with a target blood pressure below 125/75 mmHg (following current clinical guidelines). ACE-inhibitors (ARB when an ACE-inhibitor is not tolerated) Other antihypertensive medications depending on the clinical decision and following current guidelines. Statin therapy Dietary counseling for a low-sodium diet and, if GFR is below 60 ml/min, for a protein intake of 0.8 g/kg/day.<br>|
| Active Comparator: B<br> | Drug: supportive and immunosuppressive therapy<br>* supportive therapy as outlined above depending on GFR: methylprednisolone and prednisolone cyclophosphamide and prednisolone; after 3 months azathioprine with prednisolone Concomitant medication with the immunosuppressive treatment following current clinical practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients reaching full clinical remission of their disease |  | at the end of the 3 year study period. | 
| GFR loss of 15 ml/min or higher from baseline GFR |  | at the end of the 3 year study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| -Absolute GFR-change. |  | at the end of the 3 years study period | 
| GFR loss >=30 ml/min from baseline GFR |  | at the end of the 3 year study period | 
| -Onset of end stage renal disease. |  | at the end of the 3 years study period | 
| Mean annual change in one over serum creatinine concentration |  | at the end of the 3 years study period | 
| Proteinuria at 12 and 36 months |  | 12 and 36 months | 
| Disappearance of microhematuria |  | at the end of the 3 years study period |