Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

IgA Nephropathy Clinical Trial

— STOP-IgAN  

Official title:

Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554502
• Other study ID #: STOP-IgAN
• Status: Completed
• Phase: Phase 3
• First received: October 29, 2007
• Last updated: September 21, 2015
• Start date: February 2008
• Est. completion date: February 2015

Study information

• Verified date: September 2015
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

Drug:
• supportive therapy with: ACE-inhibitor / ARB / Statin
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.
• supportive and immunosuppressive therapy
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

Locations

Country	Name	City	State
Germany	Medical Clinic II, University Hospital Aachen	Aachen
Germany	2. Medizinische Klinik, Nephrologie, Klinikum Augsburg	Augsburg
Germany	Campus Charité Mitte, Medizinische Klinik - Schwerpunkt Nephrologie, Centrum 13	Berlin
Germany	Charité Campus Virchow-Klinikum, Medizinische Klinik / Nephrologie	Berlin
Germany	Helios-Klinikum Berlin-Buch, Nephrologie Charité CCB	Berlin
Germany	St. Joseph Krankenhaus Medizinische Klinik II	Berlin
Germany	Klinikum Bremen-Mitte, Medizinische Klinik III	Bremen
Germany	Universitätsklinikum Dresden, Medizinische Klinik III, Bereich Nephrologie	Dresden
Germany	Universitätsklinikum Düsseldorf, Klinik für Nephrologie	Düsseldorf
Germany	Universitätsklinikum Erlangen, Medizinische Klinik IV	Erlangen
Germany	Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten	Essen
Germany	Universitätsklinikum Freiburg, Innere Medizin IV	Freiburg
Germany	Universitätsklinikum Gießen und Marburg GmbH, Medizinische Klinik und Poliklinik II	Gießen
Germany	Universitätsklinikum Göttingen, Zentrum Innere Medizin, Abteilung für Nephrologie und Rheumatologie	Göttingen
Germany	Universitätsklinikum Hamburg-Eppendorf, 3. Medizinische Klinik und Poliklinik	Hamburg
Germany	Medizinische Hochschule Hannover, Abteilung Nephrologie	Hannover
Germany	Med. Universitätsklinik Heidelberg, Nierenzentrum Heidelberg, Sektion Nephrologie	Heidelberg
Germany	Universitätsklinikum Jena, Medizinische Klinik III	Jena
Germany	Westpfalz-Klinikum GmbH, Abteilung für Nephrologie und Transplantationsmedizin	Kaiserslautern
Germany	Uniklinik Köln, Klinik IV für Innere Medizin, Nephrologie und Allgemeine Innere Medizin	Köln
Germany	Universitätsklinikum Magdeburg, Klinik für Nephrologie, Zentrum für Innere Medizin	Magdeburg
Germany	Dialysezentrum am Brand	Mainz
Germany	Universitätsklinikum Mannheim, V. Medizinische Klinik	Mannheim
Germany	Universitätsklinikum Marburg, Klinik für Innere Medizin, Schwerpunkt Nephrologie	Marburg
Germany	KfH Nierenzentrum	München
Germany	Klinikum der LMU, Nephrologisches Zentrum	München
Germany	Klinikum rechts der Isar, Medizinische Klinik II, Abteilung für Nephrologie	München
Germany	Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D	Münster
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II	Regensburg
Germany	Krankenhaus der Barmherzigen Brüder, Abteilung Innere Medizin II	Trier
Germany	Universitätsklinikum Tübingen, Medizinische Klinik IV, Sektion für Nieren- und Hochdruckkrankheiten	Tübingen
Germany	Dialyse-Zentrum Dres.med. PD H. Reichel, Th. Weinreich u. C.	Villingen-Schwenningen
Germany	Zentrum für Nieren- und Hochdruckkrankheiten	Wiesbaden
Germany	Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik I	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
RWTH Aachen University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients reaching full clinical remission of their disease		at the end of the 3 year study period.
Primary	GFR loss of 15 ml/min or higher from baseline GFR		at the end of the 3 year study period
Secondary	-Absolute GFR-change.		at the end of the 3 years study period
Secondary	GFR loss >=30 ml/min from baseline GFR		at the end of the 3 year study period
Secondary	-Onset of end stage renal disease.		at the end of the 3 years study period
Secondary	Mean annual change in one over serum creatinine concentration		at the end of the 3 years study period
Secondary	Proteinuria at 12 and 36 months		12 and 36 months
Secondary	Disappearance of microhematuria		at the end of the 3 years study period

External Links

•   Study Homepage