Clinical trial NCT02645565: Comparison of Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Lupus Nephritis
Official title: Comparison of Intravenous Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Proliferative Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lupus Nephritis
Lead sponsor: Jawaharlal Institute of Postgraduate Medical Education & Research
Sponsor class: OTHER_GOV
First posted: 2016-01-01
Enrollment: 75
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be conducted to find out whether low dose or high dose cyclophosphamide therapy is effective in the treatment of proliferative lupus nephritis.It will also compare the side effects and risks of infection in low dose and high dose cyclophosphamide group. Half of the participants will receive a low dose cyclophosphamide for 3 months and half will receive high dose cyclophosphamide therapy monthly for 6 months followed by azathioprine 2 mg/kg.

Detailed description: The study will be conducted at the Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education \& Research (JIPMER). Once the patients are diagnosed to have systemic lupus erythematosus (SLE) lupus nephritis and they satisfy the inclusion criteria , they will be informed about the nature and severity of the disease and about the expected treatment options and the duration of treatment. After providing written informed consent, eligible patients will be stratified into two groups. Block randomization will be done to generate random allocation sequence.They will receive either a low dose or high dose Cyclophosphamide as per the protocol mentioned below:

Group I : Low dose arm : Intravenous cyclophosphamide fixed pulse 500 mg each 2 weekly total 6 doses followed by azathioprine 2 mg/kg.

Group II : High Dose arm : Intravenous cyclophosphamide therapy 750 mg/m2 will be given every 4 weekly for total 6 doses followed by azathioprine 2 mg/kg.

Intravenous methylprednisolone pulses 1 gm each will be given for 3 days in both the treatment arms followed by prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks.

Additional drugs as per indication like hydroxychloroquine, antihypertensives and cotrimoxazole prophylaxis shall also be given unless contraindicated.

There will be monitoring of treatment efficacy and side effects in each treatment arm

Eligibility criteria: Inclusion Criteria:

1. A diagnosis of SLE according to the American College of Rheumatology (ACR) criteria
2. Age \>16 years
3. Proteinuria ≥500 mg in 24 hours/ urine routine microscopy showing active cellular casts/sediments.
4. Biopsy-proven proliferative lupus glomerulonephritis of class III, IV according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.

Exclusion Criteria:

1. Patients ever treated previously with intravenous or oral cyclophosphamide or received steroids \>15mg/day in the last 3 months.
2. Patients with renal thrombotic microangiopathy, preexisting chronic renal failure, pregnancy, previous malignancy (except skin and cervical intraepithelial neoplasia), diabetes mellitus or coronary heart disease.
3. Patients with previously documented severe toxicity to immunosuppressive drugs.
4. Patients with acute/chronic infections.
5. Pregnancy

Primary outcomes:
measure: Assessment of Primary Renal Response
timeFrame: 12 months
Secondary outcomes:
measure: Proportion of patients with Renal and Non renal disease flares
timeFrame: 12 months
measure: Assessment of adverse events
timeFrame: 12 Months
Other outcomes:
Locations:
city: Pondicherry
country: India
facility: Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research
Study officials:
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Dr. Vir Singh Negi, DM
role: PRINCIPAL_INVESTIGATOR
affiliation: Jawaharlal Institute of Postgraduate Medical Education & Research
name: Dr. Sonal Mehra, MD
role: STUDY_CHAIR
References:
citation: Mehra S, Usdadiya JB, Jain VK, Misra DP, Negi VS. Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis: a single center study. Rheumatol Int. 2018 Apr;38(4):557-568. doi: 10.1007/s00296-018-3995-3. Epub 2018 Feb 15.