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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
75
Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis.
azathioprine will be given at 2 mg/kg.
Each treatment arm shall receive 1 gm methylprednisolone pulse for 3 days followed by prednisolone 1 mg/kg for 4 weeks and tapered 5 mg every 2 weekly ,to maintain 7.5 mg dose daily
Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research
Puducherry, Puducherry, India
Assessment of Primary Renal Response
Renal response as by the EULAR guidelines will be evaluated at 12 months for low dose group and high dose cyclophosphamide group. Inactive urinary sediments defined by ≤5 red blood cells (RBC)/hpf, ≤5 white blood cells (WBC)/hpf and no cellular casts as per the American college of rheumatology (ACR) definition. 1. Complete Response (CR) with urine protein creatinine ratio(UPCR) \<0.5 gm and Normal (GFR \> 90 ml/min) or stable (\<10% deterioration from baseline if GFR was previously abnormal) renal function and inactive urinary sediments. 2. Partial Response(PR) , defined as ≥50% reduction in proteinuria to subnephrotic levels , normal (GFR \> 90 ml/min) or stable (\<10% deterioration from baseline if GFR was previously abnormal) renal function and inactive urinary sediments. 3. No Response : Patients will be classified as non responders if criteria for CR or PR are not met and or if they experience severe flare.
Time frame: 12 months
Proportion of patients with Renal and Non renal disease flares
Nephritic flares consist of a reproducible increase in serum creatinine (SCr) concentration of 30% or more (or a reduction in glomerular filtration rate \[GFR\] by 10% or more) and active urine sediment with an increase in glomerular hematuria by 10 or more red blood cells per high power field, irrespective of changes in UPCR. Proteinuric flares consist of a reproducible doubling of urine protein to creatinine ratio (UPCR) to more than 1.0 after complete renal response or a reproducible doubling of UPCR to more than 2.0 after partial response.
Time frame: 12 months
Assessment of adverse events
Time frame: 12 Months
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