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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00430105
Other study ID # IC20-CT97-0019
Secondary ID BMH4-CT97-2328IC
Status Completed
Phase Phase 2/Phase 3
First received January 31, 2007
Last updated January 31, 2007
Start date February 1998
Est. completion date April 2004

Study information

Verified date January 2007
Source Cambridge University Hospitals NHS Foundation Trust
Contact n/a
Is FDA regulated No
Health authority United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 160
Est. completion date April 2004
Est. primary completion date
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 80 Years
Eligibility Inclusion Criteria:

1. A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.

2. 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.

3. 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).

4. Age 18-80 years.

Exclusion Criteria:

1. 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.

2. Co-existence of another multisystem autoimmune disease, e.g. SLE.

3. Hepatitis Be antigen positive or Hepatitis C antibody positive.

4. Known HIV positivity (HIV testing will not be a requirement for this trial).

5. Serum creatinine > 500umol/l (consider MEPEX trial).

6. Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).

7. Previous malignancy (usually exclude unless agreed with trial co-ordinator).

8. Pregnancy or inadequate contraception if female.

9. Anti-GBM antibody positivity.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
cyclophosphamide


Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Cambridge University Hospitals NHS Foundation Trust

Outcome

Type Measure Description Time frame Safety issue
Primary Disease free period, time from remission to relapse or study end.
Secondary Adverse events
Secondary Vasculitis Damage Index
Secondary Cumulative exposure to cyclophosphamide
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