Steroids and Azathioprine Versus Steroids Alone in IgAN

Study Overview
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Brief Summary
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In a previous trial the investigators found that the effect of steroids in IgA nephropathy diminish over time. The difference in renal survival is striking up till the third year, but then remains constant. A six-month course of steroid therapy may be not enough to ensure a stable remission. The investigators hypothesized that a more aggressive treatment may obtain long-term better results. The investigators conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

Detailed Description
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In 1999, we published a multicenter, randomized, controlled trial, which compared a 6-month steroid course with supportive therapy in 86 patients with IgAN. After 5 years of follow-up, the risk of a 50% increase in plasma creatinine from baseline was significantly lower in the treated patients; proteinuria also decreased. However, the effect of steroids seemed to diminish over time. The difference in renal survival was particularly striking up till the third year, but then remained constant. We hypothesised that a six-month course of steroid therapy is not enough to ensure a stable remission, and a more aggressive treatment may be required to obtain long-term better results. At this regard, some studies of combined treatment with corticosteroids and azathioprine found that treatment was effective in preserving renal function and in reducing proteinuria. However, these studies did not clarify whether azathioprine added further benefit to steroids in the long term. We conducted a randomised controlled trial to assess the utility of low-dose azathioprine added to steroids in adult IgAN patients.

Official Title
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Corticosteroids and Azathioprine Versus Corticosteroids Alone in IgA Nephropathy: a Randomized Controlled Trial.

Conditions
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IGA Nephropathy

Intervention / Treatment
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* Drug: steroids plus azathioprine
* Drug: steroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: biopsy proven IgA nephropathy creatinine ≤ 2.0 mg/dl for at least three months proteinuria ≥ 1.0 g/day for at least three months Exclusion Criteria: treatment with steroids or cytotoxic drugs during the previous three years contraindications to steroids or azathioprine Henoch-Schöenlein purpura diabetes mellitus severe hypertension (diastolic blood pressure > 120 mmHg) lupus erythematosus systemicus malignancies active peptic-ulcer disease pregnancy viral hepatitis or other infections

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Experimental: 1<br>Six month steroid course plus azathioprine | Drug: steroids plus azathioprine<br>* methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for six months<br>* Other names: azatioprina;|
| Active Comparator: 2<br>six month steroid course | Drug: steroids<br>* methylprednisolone 1 g i.v. for three consecutive days at the beginning of months 1, 3 and 5, followed by oral prednisone 0.5 mg/kg every other day for six months<br>* Other names: deltacortene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression of renal disease, estimated by the time to 50% increase in plasma creatinine from baseline. |  | Every month for the first six months, then six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evolution of proteinuria over time |  | every months for the first six months and then every six months | 
| safety |  | every months for the first six months and then every six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA nephropathy, steroids, azathioprine, chronic kidney disease progression, proteinuria