Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

Phase 3

Completed

• Conditions: IgA Nephropathy
• Interventions: Drug: supportive and immunosuppressive therapy

• Registration Number: NCT00554502
• Lead Sponsor: RWTH Aachen University

Brief Summary

* 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

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).

Study Timeline

• Study First Submitted: 2007-10-29
• Study First Submitted QC: 2007-11-05
• Study First Posted: 2007-11-07
• Study Start: 2008-02
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-21
• Last Update Posted: 2015-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 148

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

  1. arterial hypertension, defined as ambulatory blood pressure >140/90 mm Hg or the use of antihypertensive medication or
  2. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	supportive and immunosuppressive therapy	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
-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
GFR loss >=30 ml/min from baseline GFR	at the end of the 3 year study period
-Absolute GFR-change.	at the end of the 3 years study period

Trial Locations

Locations (34)

St. Joseph Krankenhaus Medizinische Klinik II; 🇩🇪 Berlin, Germany

2. Medizinische Klinik, Nephrologie, Klinikum Augsburg; 🇩🇪 Augsburg, Germany

Universitätsklinikum Göttingen, Zentrum Innere Medizin, Abteilung für Nephrologie und Rheumatologie; 🇩🇪 Göttingen, Germany

Universitätsklinikum Jena, Medizinische Klinik III; 🇩🇪 Jena, Germany

Universitätsklinikum Erlangen, Medizinische Klinik IV; 🇩🇪 Erlangen, Germany

KfH Nierenzentrum; 🇩🇪 München, Germany

Medical Clinic II, University Hospital Aachen; 🇩🇪 Aachen, Germany

Universitätsklinikum Düsseldorf, Klinik für Nephrologie; 🇩🇪 Düsseldorf, Germany

Helios-Klinikum Berlin-Buch, Nephrologie Charité CCB; 🇩🇪 Berlin, Germany

Med. Universitätsklinik Heidelberg, Nierenzentrum Heidelberg, Sektion Nephrologie; 🇩🇪 Heidelberg, Germany

Klinikum Bremen-Mitte, Medizinische Klinik III; 🇩🇪 Bremen, Germany

Westpfalz-Klinikum GmbH, Abteilung für Nephrologie und Transplantationsmedizin; 🇩🇪 Kaiserslautern, Germany

Universitätsklinikum Mannheim, V. Medizinische Klinik; 🇩🇪 Mannheim, Germany

Dialysezentrum am Brand; 🇩🇪 Mainz, Germany

Campus Charité Mitte, Medizinische Klinik - Schwerpunkt Nephrologie, Centrum 13; 🇩🇪 Berlin, Germany

Charité Campus Virchow-Klinikum, Medizinische Klinik / Nephrologie; 🇩🇪 Berlin, Germany

Universitätsklinikum Hamburg-Eppendorf, 3. Medizinische Klinik und Poliklinik; 🇩🇪 Hamburg, Germany

Universitätsklinikum Gießen und Marburg GmbH, Medizinische Klinik und Poliklinik II; 🇩🇪 Gießen, Germany

Medizinische Hochschule Hannover, Abteilung Nephrologie; 🇩🇪 Hannover, Germany

Universitätsklinikum Magdeburg, Klinik für Nephrologie, Zentrum für Innere Medizin; 🇩🇪 Magdeburg, Germany

Universitätsklinikum Freiburg, Innere Medizin IV; 🇩🇪 Freiburg, Germany

Universitätsklinikum Marburg, Klinik für Innere Medizin, Schwerpunkt Nephrologie; 🇩🇪 Marburg, Germany

Klinikum der LMU, Nephrologisches Zentrum; 🇩🇪 München, Germany

Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D; 🇩🇪 Münster, Germany

Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II; 🇩🇪 Regensburg, Germany

Dialyse-Zentrum Dres.med. PD H. Reichel, Th. Weinreich u. C.; 🇩🇪 Villingen-Schwenningen, Germany

Krankenhaus der Barmherzigen Brüder, Abteilung Innere Medizin II; 🇩🇪 Trier, Germany

Universitätsklinikum Tübingen, Medizinische Klinik IV, Sektion für Nieren- und Hochdruckkrankheiten; 🇩🇪 Tübingen, Germany

Zentrum für Nieren- und Hochdruckkrankheiten; 🇩🇪 Wiesbaden, Germany

Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik I; 🇩🇪 Würzburg, Germany

Klinikum rechts der Isar, Medizinische Klinik II, Abteilung für Nephrologie; 🇩🇪 München, Germany

Uniklinik Köln, Klinik IV für Innere Medizin, Nephrologie und Allgemeine Innere Medizin; 🇩🇪 Köln, Germany

Universitätsklinikum Dresden, Medizinische Klinik III, Bereich Nephrologie; 🇩🇪 Dresden, Germany

Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten; 🇩🇪 Essen, Germany