Supportive Versus Immunosuppressive Therapy for the Treatment Of Progressive IgA Nephropathy

NCT00554502 | Completed Phase 3 DMC

• 1 other identifier: STOP-IgAN
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 34

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.

Conditions

IgA Nephropathy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• -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

Study Arms (2)

A

ACTIVE COMPARATOR

Drug: supportive therapy with: ACE-inhibitor / ARB / Statin

B

ACTIVE COMPARATOR

Drug: supportive and immunosuppressive therapy

Interventions

supportive therapy with: ACE-inhibitor / ARB / Statin DRUG

* 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.

A

supportive and immunosuppressive therapy DRUG

* 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

B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (34)

Medical Clinic II, University Hospital Aachen

Aachen, Germany

Location

2. Medizinische Klinik, Nephrologie, Klinikum Augsburg

Augsburg, Germany

Location

Campus Charité Mitte, Medizinische Klinik - Schwerpunkt Nephrologie, Centrum 13

Berlin, Germany

Location

Charité Campus Virchow-Klinikum, Medizinische Klinik / Nephrologie

Berlin, Germany

Location

Helios-Klinikum Berlin-Buch, Nephrologie Charité CCB

Berlin, Germany

Location

St. Joseph Krankenhaus Medizinische Klinik II

Berlin, Germany

Location

Klinikum Bremen-Mitte, Medizinische Klinik III

Bremen, Germany

Location

Uniklinik Köln, Klinik IV für Innere Medizin, Nephrologie und Allgemeine Innere Medizin

Cologne, Germany

Location

Universitätsklinikum Dresden, Medizinische Klinik III, Bereich Nephrologie

Dresden, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Nephrologie

Düsseldorf, Germany

Location

Universitätsklinikum Erlangen, Medizinische Klinik IV

Erlangen, Germany

Location

Universitätsklinikum Essen, Klinik für Nieren- und Hochdruckkrankheiten

Essen, Germany

Location

Universitätsklinikum Freiburg, Innere Medizin IV

Freiburg im Breisgau, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH, Medizinische Klinik und Poliklinik II

Giessen, Germany

Location

Universitätsklinikum Göttingen, Zentrum Innere Medizin, Abteilung für Nephrologie und Rheumatologie

Göttingen, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, 3. Medizinische Klinik und Poliklinik

Hamburg, Germany

Location

Medizinische Hochschule Hannover, Abteilung Nephrologie

Hanover, Germany

Location

Med. Universitätsklinik Heidelberg, Nierenzentrum Heidelberg, Sektion Nephrologie

Heidelberg, Germany

Location

Universitätsklinikum Jena, Medizinische Klinik III

Jena, Germany

Location

Westpfalz-Klinikum GmbH, Abteilung für Nephrologie und Transplantationsmedizin

Kaiserslautern, Germany

Location

Universitätsklinikum Magdeburg, Klinik für Nephrologie, Zentrum für Innere Medizin

Magdeburg, Germany

Location

Dialysezentrum am Brand

Mainz, Germany

Location

Universitätsklinikum Mannheim, V. Medizinische Klinik

Mannheim, Germany

Location

Universitätsklinikum Marburg, Klinik für Innere Medizin, Schwerpunkt Nephrologie

Marburg, Germany

Location

KfH Nierenzentrum

München, Germany

Location

Klinikum der LMU, Nephrologisches Zentrum

München, Germany

Location

Klinikum rechts der Isar, Medizinische Klinik II, Abteilung für Nephrologie

München, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D

Münster, Germany

Location

Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin II

Regensburg, Germany

Location

Krankenhaus der Barmherzigen Brüder, Abteilung Innere Medizin II

Trier, Germany

Location

Universitätsklinikum Tübingen, Medizinische Klinik IV, Sektion für Nieren- und Hochdruckkrankheiten

Tübingen, Germany

Location

Dialyse-Zentrum Dres.med. PD H. Reichel, Th. Weinreich u. C.

Villingen-Schwenningen, Germany

Location

Zentrum für Nieren- und Hochdruckkrankheiten

Wiesbaden, Germany

Location

Universitätsklinik Würzburg, Medizinische Klinik und Poliklinik I

Würzburg, Germany

Location

Related Publications (5)

• Alladin A, Hahn D, Hodson EM, Ravani P, Pfister K, Quinn RR, Samuel SM. Immunosuppressive therapy for IgA nephropathy in children. Cochrane Database Syst Rev. 2024 Jun 12;6(6):CD015060. doi: 10.1002/14651858.CD015060.pub2.

  PMID: 38864363 DERIVED

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

  PMID: 38299639 DERIVED

• 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.

  PMID: 26630142 DERIVED

• 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.

  PMID: 26032537 DERIVED

• 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.

  PMID: 18587715 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Palliative Care; Immunosuppression Therapy

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Immunotherapy; Immunomodulation; Biological Therapy; Immunologic Techniques; Investigative Techniques

Study Officials

• Juergen Floege, Prof. Dr.

  Medical Clinic II, University Hospital Aachen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: November 7, 2007
• Study Start: February 1, 2008
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: September 22, 2015

Record last verified: 2015-09

Locations

DE (34)