Anti-Cytokine Therapy for Vasculitis (ACTIVE)

This study has been completed.
Sponsor:
Information provided by:
University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00753103
First received: September 15, 2008
Last updated: NA
Last verified: September 2008
History: No changes posted
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital Birmingham NHS Foundation Trust:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events [ Time Frame: Weeks 2, 6, 10, 14, 26, 39, 52 ] [ Designated as safety issue: Yes ]
  • Vasculitis Damage Index Score [ Time Frame: Weeks 0, 14, 26, 39, 52 ] [ Designated as safety issue: No ]
  • Renal function [ Time Frame: Weeks 0, 2, 6, 10, 14, 26, 39, 52 ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: January 2003
Study Completion Date: July 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753103

Locations
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
Principal Investigator: Lorraine Harper, PhD University of Birmingham
  More Information

No publications provided

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
Study First Received: September 15, 2008
Last Updated: September 15, 2008
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University Hospital Birmingham NHS Foundation Trust:
Infliximab
Vasculitis
antitnf monoclonal antibody

Additional relevant MeSH terms:
Microscopic Polyangiitis
Systemic Vasculitis
Vasculitis
Wegener Granulomatosis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Immune System Diseases
Lung Diseases
Lung Diseases, Interstitial
Nervous System Diseases
Respiratory Tract Diseases
Vascular Diseases
Azathioprine
Cyclophosphamide
Infliximab
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Mycophenolate mofetil
Mycophenolic Acid
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Alkylating Agents

ClinicalTrials.gov processed this record on October 23, 2014