Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
Primary Purpose
ANCA Associated Systemic Vasculitis, Wegener's Granulomatosis, Microscopic Polyangiitis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for ANCA Associated Systemic Vasculitis focused on measuring Vasculitis, ANCA, Wegener's granulomatosis, Renal vasculitis, Cyclophosphamide
Eligibility Criteria
Inclusion Criteria:
- A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.
Renal involvement attributable to active WG, MP or RLV with at least one of the following:
- elevated serum creatinine between 150 and 500 umol/l.
- biopsy demonstrating necrotizing glomerulonephritis.
- red cell casts.
- haematuria with >30 red blood cells/high powered field and proteinuria > 1g/24hr.
- ANCA positivity or confirmatory histology or both (appendix 5). ANCA positivity requires a typical CANCA pattern by indirect immunofluorescence (IIF), (preferably confirmed by anti-PR3 ELISA), or the presence of PR3-ANCA or MPO-ANCA determined by ELISA, PANCA requires confirmation by anti-MPO ELISA [6]. (Central review of ANCA serology and histology will be performed).
- Age 18-80 years.
Exclusion Criteria:
- More than two weeks treatment with cyclophosphamide (CYC) or other cytotoxic drug within previous year or with oral corticosteroids (OCS) for more than 4 weeks. If the patient has received >1.0g of methyl-prednisolone prior to the study start, discuss with trial co-ordinator.
- Co-existence of another multisystem autoimmune disease, e.g. SLE.
- Hepatitis Be antigen positive or Hepatitis C antibody positive.
- Known HIV positivity (HIV testing will not be a requirement for this trial).
- Serum creatinine > 500umol/l (consider MEPEX trial).
- Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).
- Previous malignancy (usually exclude unless agreed with trial co-ordinator).
- Pregnancy or inadequate contraception if female.
- Anti-GBM antibody positivity.
Sites / Locations
Outcomes
Primary Outcome Measures
Disease free period, time from remission to relapse or study end.
Secondary Outcome Measures
Adverse events
Vasculitis Damage Index
Cumulative exposure to cyclophosphamide
Full Information
NCT ID
NCT00430105
First Posted
January 31, 2007
Last Updated
January 31, 2007
Sponsor
Cambridge University Hospitals NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT00430105
Brief Title
Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
Official Title
Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides
Study Type
Interventional
2. Study Status
Record Verification Date
January 2007
Overall Recruitment Status
Completed
Study Start Date
February 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2004 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Cambridge University Hospitals NHS Foundation Trust
4. Oversight
5. Study Description
Brief Summary
A comparison of intermittent pulsed cyclophosphamide to daily oral cyclophosphamide for the treatment of ANCA-associated systemic vasculitides with kidney involvement.
Performed by the European Vasculitis Study group.
Detailed Description
The primary, ANCA-associated systemic vasculitides (AASV), including Wegener's granulomatosis and microscopic polyangiitis, are progressive, multisystem, autoimmune diseases which respond to immunosuppressive therapy. Their treatment with corticosteroids and cytotoxic drugs has been standardised in a first wave of studies (ECSYSVASTRIAL project), but limitations of such regimens include only partial efficacy and appreciable treatment-related toxicity.
The present trial, CYCLOPS, aims to reduce the cumulative exposure to immunosuppressive drugs by administering cyclophosphamide (CYC) as intermittent pulses. The potential benefit of using CYC in this way for AASV has been demonstrated in preliminary, smaller studies. Patients with previously untreated AASV and, "generalised", but not life threatening, disease with renal involvement, will be randomised to either continuous oral CYC or intermittent pulse CYC. CYC will be continued until three months after remission has been achieved, with a minimum CYC total duration of six months and maximum duration of twelve months; both limbs will then receive the same maintenance regimen of azathioprine and prednisolone.
The study will last 18 months. The primary end-point is the disease-free period, taken as the period of time from remission until relapse or study end; secondary end-points are adverse effects, cumulative damage and immunosuppressive drug exposure. 160 patients will be required.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ANCA Associated Systemic Vasculitis, Wegener's Granulomatosis, Microscopic Polyangiitis
Keywords
Vasculitis, ANCA, Wegener's granulomatosis, Renal vasculitis, Cyclophosphamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Primary Outcome Measure Information:
Title
Disease free period, time from remission to relapse or study end.
Secondary Outcome Measure Information:
Title
Adverse events
Title
Vasculitis Damage Index
Title
Cumulative exposure to cyclophosphamide
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.
Renal involvement attributable to active WG, MP or RLV with at least one of the following:
elevated serum creatinine between 150 and 500 umol/l.
biopsy demonstrating necrotizing glomerulonephritis.
red cell casts.
haematuria with >30 red blood cells/high powered field and proteinuria > 1g/24hr.
ANCA positivity or confirmatory histology or both (appendix 5). ANCA positivity requires a typical CANCA pattern by indirect immunofluorescence (IIF), (preferably confirmed by anti-PR3 ELISA), or the presence of PR3-ANCA or MPO-ANCA determined by ELISA, PANCA requires confirmation by anti-MPO ELISA [6]. (Central review of ANCA serology and histology will be performed).
Age 18-80 years.
Exclusion Criteria:
More than two weeks treatment with cyclophosphamide (CYC) or other cytotoxic drug within previous year or with oral corticosteroids (OCS) for more than 4 weeks. If the patient has received >1.0g of methyl-prednisolone prior to the study start, discuss with trial co-ordinator.
Co-existence of another multisystem autoimmune disease, e.g. SLE.
Hepatitis Be antigen positive or Hepatitis C antibody positive.
Known HIV positivity (HIV testing will not be a requirement for this trial).
Serum creatinine > 500umol/l (consider MEPEX trial).
Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).
Previous malignancy (usually exclude unless agreed with trial co-ordinator).
Pregnancy or inadequate contraception if female.
Anti-GBM antibody positivity.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirsten de Groot
Organizational Affiliation
Klinikum Offenbach GmbH, Germany
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Caroline OS Savage
Organizational Affiliation
University of Birmingham
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
PubMed Identifier
28592297
Citation
Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, Hiemstra TF, Flossmann O, Berden A, Hoglund P, Harper L; European Vasculitis Society. Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Res Ther. 2017 Jun 7;19(1):129. doi: 10.1186/s13075-017-1321-1.
Results Reference
derived
PubMed Identifier
19451574
Citation
de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80. doi: 10.7326/0003-4819-150-10-200905190-00004.
Results Reference
derived
Learn more about this trial
Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
We'll reach out to this number within 24 hrs