ANCA Associated Systemic VasculitisPhase 2/3NCT00430105
Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
A Phase 2/3 study testing cyclophosphamide in people with ANCA Associated Systemic Vasculitis and Wegener's Granulomatosis, run by Cambridge University Hospitals NHS Foundation Trust.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- ANCA Associated Systemic Vasculitis, Wegener's Granulomatosis, Microscopic Polyangiitis
- What is being tested?
- cyclophosphamide
- How many people
- 160 participants
- Where
- No sites listed yet
- Study dates
- Feb 1998to Apr 2004
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- Previous malignancy (usually exclude unless agreed with trial co-ordinator).
- Pregnancy or inadequate contraception if female.
- Anti-GBM antibody positivity.
About this study
Official title: Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides
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.
Read the 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.
- Being tested
- cyclophosphamide
- Keywords
- Vasculitis, ANCA, Wegener's granulomatosis, Renal vasculitis, Cyclophosphamide
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free period, time from remission to relapse or study end.
Secondary outcomes (3)
Adverse events
Vasculitis Damage Index
Cumulative exposure to cyclophosphamide
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2007 (estimated)
- Study startFeb 1998
- Study completionApr 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ANCA Associated Systemic VasculitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Investigators
- Kirsten de Groot, Study chair, Klinikum Offenbach GmbH, GermanyCaroline OS Savage, Study chair, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00430105
- Sponsor's protocol ID
- IC20-CT97-0019
- Other IDs
- BMH4-CT97-2328, IC20-CT97-0019
- Status last verified
- Jan 2007
- First submitted
- 31 Jan 2007
- Last updated
- 1 Feb 2007
- Results posted
- No
Publications
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.
PubMed 28592297de 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.
PubMed 19451574
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides
- ClinicalTrials.gov ID
- NCT00430105
- Acronym / sponsor ID
- IC20-CT97-0019
- Keywords
- Vasculitis, ANCA, Wegener's granulomatosis, Renal vasculitis, Cyclophosphamide
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- Feb 1998
- Study completion
- Apr 2004
- First posted
- 1 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- 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.
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamide | Drug | – |
Primary outcome
Disease free period, time from remission to relapse or study end.
3 secondary outcomes
Adverse events
Vasculitis Damage Index
Cumulative exposure to cyclophosphamide
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2007.
- Derived from this study: PubMed 28592297Morgan 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.
- Derived from this study: PubMed 19451574de 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kirsten de Groot study chair
Klinikum Offenbach GmbH, Germany
Caroline OS Savage study chair
University of Birmingham
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing cyclophosphamide in people with ANCA Associated Systemic Vasculitis and Wegener's Granulomatosis, run by Cambridge University Hospitals NHS Foundation Trust.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2007. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free period, time from remission to relapse or study end.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00430105, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2007.