Anti-Cytokine Therapy for Vasculitis (ACTIVE)

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ClinicalTrials.gov Identifier: NCT00753103

Recruitment Status : Completed

First Posted : September 16, 2008

Last Update Posted : September 16, 2008

Sponsor:

Information provided by:

University Hospital Birmingham NHS Foundation Trust

Study Description

Brief Summary:

The purpose of this study is to determine whether Infliximab (monoclonal anti-tumour necrosis factor alpha antibodies) are safe and effective in the treatment of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis.

Condition or disease	Intervention/treatment	Phase
Wegener's Granulomatosis Renal Limited Vasculitis Microscopic Polyangiitis	Biological: Infliximab Drug: Cyclophosphamide Drug: Prednisolone Drug: Azathioprine Procedure: Plasma exchange Drug: Mycophenolate mofetil Drug: Methylprednisolone	Phase 2

Detailed Description:

Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis is a life-threatening systemic inflammatory autoimmune disease. Current treatment regimes using corticosteroids and cyclophosphamide have improved patient survival but are associated with treatment associated morbidity and mortality. Tumour necrosis factor alpha (TNF) is a proinflammatory cytokine which has been implicated in the pathogenesis of ANCA vasculitis. Anti-TNF therapies have been used successfully in the management of other inflammatory autoimmune diseases. This phase II cohort study has been designed to investigate the safety and efficacy of anti-TNF monoclonal antibody (Infliximab) therapy for patients with ANCA associated vasculitis when used in addition to standard immunosuppressive therapy.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	37 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Pilot Cohort Study to Investigate the Safety and Efficacy of Infliximab as Additional Therapy in the Treatment if Anti-Neutrophil Cytoplasm Antibody Associated Vasculitis
Study Start Date :	January 2003
Actual Primary Completion Date :	July 2006
Actual Study Completion Date :	July 2006

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Granulomatosis with polyangiitis

MedlinePlus related topics: Vasculitis

Drug Information available for: Infliximab

Genetic and Rare Diseases Information Center resources: Granulomatosis With Polyangiitis Microscopic Polyangiitis ANCA-associated Vasculitis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Patients with active vasculitis who receive infliximab in addition to standard immunosuppressive therapy	Biological: Infliximab 5 mg/kg intravenous infusion at weeks 0, 2, 6 and 10 of study Other Name: Remicade Drug: Cyclophosphamide Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months). Drug: Prednisolone Daily oral 1mg/kg tapered over 12 months Drug: Azathioprine Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued. Drug: Mycophenolate mofetil Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion. Drug: Methylprednisolone 500 mg intravenous infusion daily for three days at lead physicians discretion.
Active Comparator: 2 Patients with active ANCA associated vasculitis who receive standard immunosuppression but no infliximab	Drug: Cyclophosphamide Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months). Drug: Prednisolone Daily oral 1mg/kg tapered over 12 months Drug: Azathioprine Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued. Procedure: Plasma exchange Additional therapy for patients with severe vasculitis (creatinine > 500 mcmol/L or pulmonary haemorrhage). 7x 4L exchanges over 10 days. Drug: Mycophenolate mofetil Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion. Drug: Methylprednisolone 500 mg intravenous infusion daily for three days at lead physicians discretion.

Arm

Intervention/treatment

Experimental: 1

Patients with active vasculitis who receive infliximab in addition to standard immunosuppressive therapy

Biological: Infliximab

5 mg/kg intravenous infusion at weeks 0, 2, 6 and 10 of study

Other Name: Remicade

Drug: Cyclophosphamide

Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months).

Drug: Prednisolone

Daily oral 1mg/kg tapered over 12 months

Drug: Azathioprine

Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued.

Drug: Mycophenolate mofetil

Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion.

Drug: Methylprednisolone

500 mg intravenous infusion daily for three days at lead physicians discretion.

Active Comparator: 2

Patients with active ANCA associated vasculitis who receive standard immunosuppression but no infliximab

Drug: Cyclophosphamide

Daily oral 2 mg/kg or pulsed intravenous 15mg/kg every 2-3 weeks for 3-6 months (until patient has been in remission for 3 months).

Drug: Prednisolone

Daily oral 1mg/kg tapered over 12 months

Drug: Azathioprine

Daily oral 2 mg/kg started once patient is in remission and cyclophosphamide has been discontinued.

Procedure: Plasma exchange

Additional therapy for patients with severe vasculitis (creatinine > 500 mcmol/L or pulmonary haemorrhage). 7x 4L exchanges over 10 days.

Drug: Mycophenolate mofetil

Daily oral up to 1.5 g twice daily as tolerated. Used as alternative to azathioprine at lead physicians discretion.

Drug: Methylprednisolone

500 mg intravenous infusion daily for three days at lead physicians discretion.

Outcome Measures

Primary Outcome Measures :

Time to clinical remission (Birmingham Vasculitis Activity Score 0 or 1) [ Time Frame: 0, 6, 10, 14, 26, 39 and 52 weeks ]

Secondary Outcome Measures :

Adverse events [ Time Frame: Weeks 2, 6, 10, 14, 26, 39, 52 ]
Vasculitis Damage Index Score [ Time Frame: Weeks 0, 14, 26, 39, 52 ]
Renal function [ Time Frame: Weeks 0, 2, 6, 10, 14, 26, 39, 52 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Either newly diagnosed or relapsed ANCA associated vasculitis (Wegener's granulomatosis, microscopic polyangiitis, renal limited vasculitis)

Exclusion Criteria:

Active infection
Malignancy
Pregnancy
Diagnosis of Churg-Strauss syndrome or anti-glomerular basement membrane antibody disease

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00753103

Locations

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United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, West Midlands, United Kingdom, B15 2TT

Sponsors and Collaborators

University Hospital Birmingham NHS Foundation Trust

Investigators

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Principal Investigator:	Lorraine Harper, PhD	University of Birmingham

More Information

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Responsible Party:	Dr Lorraine Harper, University Hospitals Birmingham NHS Foundation Trust/University of Birmingham
ClinicalTrials.gov Identifier:	NCT00753103 History of Changes
Other Study ID Numbers:	RRK2031
First Posted:	September 16, 2008 Key Record Dates
Last Update Posted:	September 16, 2008
Last Verified:	September 2008

Keywords provided by University Hospital Birmingham NHS Foundation Trust:


Infliximab Vasculitis antitnf monoclonal antibody

Additional relevant MeSH terms:

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Granulomatosis with Polyangiitis Microscopic Polyangiitis Vasculitis Vascular Diseases Cardiovascular Diseases Systemic Vasculitis Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Autoimmune Diseases Immune System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Brain Diseases	Central Nervous System Diseases Nervous System Diseases Mycophenolic Acid Prednisolone Methylprednisolone Cyclophosphamide Azathioprine Infliximab Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action

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