Anti-Cytokine Therapy for Vasculitis (ACTIVE)

September 15, 2008 updated by: University Hospital Birmingham NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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.
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.
Procedure: Plasma exchange
Additional therapy for patients with severe vasculitis (creatinine > 500 mcmol/L or pulmonary haemorrhage). 7x 4L exchanges over 10 days.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Birmingham NHS Foundation Trust

Investigators

  • Principal Investigator: Lorraine Harper, PhD, University of Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

July 1, 2006

Study Completion (Actual)

July 1, 2006

Study Registration Dates

First Submitted

September 15, 2008

First Submitted That Met QC Criteria

September 15, 2008

First Posted (Estimate)

September 16, 2008

Study Record Updates

Last Update Posted (Estimate)

September 16, 2008

Last Update Submitted That Met QC Criteria

September 15, 2008

Last Verified

September 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RRK2031

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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