CYCLONES - CYClophosphamide LOw Dose and No Extra Steroid

Summary

Glucocorticoids (GC) use has increased survival of patients with systemic lupus erythematosus (SLE), particularly in cases of nephritis and a more significant improvement to 80% with the introduction of therapy combined with immunosuppressants. This therapeutic scheme, however, results in a very high incidence of irreversible damage that is associated in more than 70% of the cases to GC use and in a smaller proportion to the use of high dose cyclophosphamide.

CYCLONES is a Controlled Randomized Clinical Trial with the aim of evaluating the efficacy of a regimen for lupus nephritis treatment using only intravenous corticosteroid administration. This intravenous corticosteroid regimen has already been tested (with Rituximab instead of Cyclophosphamide) with high response rates for lupus nephritis and significant reduction of side effects.

After selection, patients will be randomized in two arms: 116 patients will receive Euro-Lupus nephritis regimen and other 116 will undergo treatment with CYCLONES regimen.

The primary endpoint is the partial response (protein/creatinine ratio \< 3 with decrease at least of 50% of the initial value and increase of creatinine not higher than 15% of the initial value) or complete response (protein/creatinine ratio \< 500 with decrease at least of 50% of the initial value and increase of creatinine not higher than 15% of the initial value in 6 months. Secondary outcome measures will be evaluated such as osteoporosis and bone metabolism parameters, ophthalmologic evaluation of the collateral effects related to glucocorticoids, lipid profile and therapy adherence.

Conditions

• Systemic Lupus Erythematosus (SLE)

Interventions

DRUG

Cyclophosphamide

Patients in both EUROLUPUS group and CYCLONES Group will receive for 3 months Cyclophosphamide (6 doses of 500mg/biweekly)

DRUG

Methylprednisolone

Patients in EUROLUPUS group will receive Methylprednisolone \[750 mg for three consecutive days). Patients in CYCLONES Group will receive Methylprednisolone \[500 mg (day 0 and day 15), 250 mg (day 30 and day 45) and 125 mg (day 60 and day 75).

DRUG

Prednisone

Patients in EUROLUPUS group will receive oral prednisone ≤ 30 mg/day with a reduction of 5mg/month until complete withdrawal.

DRUG

Mycophenolate Mofetil

From the third month of protocol, patients in both EUROLUPUS group and CYCLONES Group will receive mycophenolate mofetil (2-3 g/day) until the sixth month of study.

Sponsors & Collaborators

• Fundação de Amparo à Pesquisa do Estado de São Paulo

  collaborator OTHER_GOV

• University of Sao Paulo General Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-04-12

Primary Completion

2021-07-02

Completion

2021-07-02

Countries

• Brazil

Study Locations