CYCLONES - CYClophosphamide LOw Dose and No Extra Steroid

• Status: Terminated
• Trial end date: 2021-07-02
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sao Paulo General Hospital
• Collaborator: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Treatments: Cyclophosphamide; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone

Criteria

Inclusion Criteria:

All the criteria below have to be completed:

1. Systemic lupus erythematosus (SLE) according to the American College of Rheumatology (ACR) classification criteria and/or SLICC: according to the thematic protocol (Petri M, et al., Arthritis Rheum, 2012);

2. Age ≥18 years;

3. Lupus Glomerulonephritis Class III, IV or V according to the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification confirmed on renal biopsy (according to the routine protocol of our outpatient clinic) performed up to 3 months to 1 year prior to selection;

4. Menopause or use contraception method;

5. Informed consent.

Exclusion Criteria:

1. Creatinine clearance < 40 ml/min calculated (Cockcroft & Gault);

2. Intolerance to medication;

3. Absolute neutrophil count < 1,000/mm3;

4. Pregnancy or breastfeeding;

5. Infection requiring hospitalization;

6. Patients who used Cyclophosphamide in the last 6 months or biological in the last year;

7. Thrombotic renal microangiopathy;

8. Chronic terminal renal disease and/or class VI biopsy;

9. Non-adhesion profile;

10. Need to use another therapeutic scheme;

11. GC dose in the last 3 months not greater than 20mg/day.

11.Central nervous system (CNS) disorders or hemolytic anemia and severe thrombocytopenia (< 50,000 platelets/mm3).