Comparison of Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Lupus Nephritis

Lupus Nephritis Clinical Trial

Official title:

Comparison of Intravenous Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Proliferative Lupus Nephritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02645565
• Other study ID #: JIP/IEC/SC/2013/5/435
• Status: Completed
• Phase: Phase 4
• First received: December 30, 2015
• Last updated: March 2, 2017
• Start date: December 2015
• Est. completion date: December 2016

Study information

• Verified date: March 2017
• Source: Jawaharlal Institute of Postgraduate Medical Education & Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Cyclophosphamide
Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis.
• Azathioprine
azathioprine will be given at 2 mg/kg.
• Methylprednisolone
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

Locations

Country	Name	City	State
India	Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research	Pondicherry

Sponsors (1)

Lead Sponsor	Collaborator
Jawaharlal Institute of Postgraduate Medical Education & Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.; 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.; 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.; 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.	12 months
Secondary	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.	12 months
Secondary	Assessment of adverse events		12 Months