Clinical trial NCT00554502: Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy
Official title: Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: IgA Nephropathy
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2007-11-07
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Patients reaching full clinical remission of their disease
timeFrame: at the end of the 3 year study period.
measure: GFR loss of 15 ml/min or higher from baseline GFR
timeFrame: at the end of the 3 year study period
Secondary outcomes:
measure: -Absolute GFR-change.
timeFrame: at the end of the 3 years study period
measure: GFR loss >=30 ml/min from baseline GFR
timeFrame: at the end of the 3 year study period
measure: -Onset of end stage renal disease.
timeFrame: at the end of the 3 years study period
measure: Mean annual change in one over serum creatinine concentration
timeFrame: at the end of the 3 years study period
measure: Proteinuria at 12 and 36 months
timeFrame: 12 and 36 months
measure: Disappearance of microhematuria
timeFrame: at the end of the 3 years study period
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Medical Clinic II, University Hospital Aachen
city: Augsburg
country: Germany
facility: 2. Medizinische Klinik, Nephrologie, Klinikum Augsburg
city: Berlin
country: Germany
facility: Campus Charité Mitte, Medizinische Klinik - Schwerpunkt Nephrologie, Centrum 13
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum, Medizinische Klinik / Nephrologie
city: Berlin
country: Germany
facility: Helios-Klinikum Berlin-Buch, Nephrologie Charité CCB
city: Berlin
country: Germany
facility: St. Joseph Krankenhaus Medizinische Klinik II
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte, Medizinische Klinik III
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden, Medizinische Klinik III, Bereich Nephrologie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Nephrologie
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Medizinische Klinik IV
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Innere Medizin IV
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH, Medizinische Klinik und Poliklinik II
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen, Zentrum Innere Medizin, Abteilung für Nephrologie und Rheumatologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, 3. Medizinische Klinik und Poliklinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Abteilung Nephrologie
city: Heidelberg
country: Germany
facility: Med. Universitätsklinik Heidelberg, Nierenzentrum Heidelberg, Sektion Nephrologie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Medizinische Klinik III
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH, Abteilung für Nephrologie und Transplantationsmedizin
city: Köln
country: Germany
facility: Uniklinik Köln, Klinik IV für Innere Medizin, Nephrologie und Allgemeine Innere Medizin
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg, Klinik für Nephrologie, Zentrum für Innere Medizin
city: Mainz
country: Germany
facility: Dialysezentrum am Brand
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, V. Medizinische Klinik
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg, Klinik für Innere Medizin, Schwerpunkt Nephrologie
city: München
country: Germany
facility: KfH Nierenzentrum
city: München
country: Germany
facility: Klinikum der LMU, Nephrologisches Zentrum
city: München
country: Germany
facility: Klinikum rechts der Isar, Medizinische Klinik II, Abteilung für Nephrologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder, Abteilung Innere Medizin II
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Medizinische Klinik IV, Sektion für Nieren- und Hochdruckkrankheiten
city: Villingen-Schwenningen
country: Germany
facility: Dialyse-Zentrum Dres.med. PD H. Reichel, Th. Weinreich u. C.
city: Wiesbaden
country: Germany
facility: Zentrum für Nieren- und Hochdruckkrankheiten
city: Würzburg
country: Germany
facility: Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik I
Study officials:
affiliation: Medical Clinic II, University Hospital Aachen
name: Juergen Floege, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J; STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36. doi: 10.1056/NEJMoa1415463.
citation: Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
citation: Eitner F, Ackermann D, Hilgers RD, Floege J. Supportive Versus Immunosuppressive Therapy of Progressive IgA nephropathy (STOP) IgAN trial: rationale and study protocol. J Nephrol. 2008 May-Jun;21(3):284-9.