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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low dose Cyclophosphamide | Active Comparator | Intravenous Cyclophosphamide therapy 500 mg intravenous 2 weekly for 3 months followed by azathioprine 2 mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day. |
|
| High Dose Cyclophosphamide | Active Comparator | Intravenous Cyclophosphamide therapy 750mg/m2 intravenous 4 weekly for 6 months followed by azathioprine 2mg/kg. Injectable methylprednisolone 1 gm pulse will be given for 3 days before starting the first pulse of cyclophosphamide followed by oral prednisolone 1 mg/kg for 4 weeks and then tapering 5 mg every 2 weeks till 7.5 mg/day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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.
| 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dr. Vir Singh Negi, DM | Jawaharlal Institute of Postgraduate Medical Education & Research | Principal Investigator |
| Dr. Sonal Mehra, MD | Jawaharlal Institute of Postgraduate Medical Education & Research | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research | Puducherry | Puducherry | 605006 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29450636 | Derived | 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. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Feb 12, 2021 | |
| Reset | Mar 5, 2021 |
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| Azathioprine | Drug | azathioprine will be given at 2 mg/kg. |
|
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| Methylprednisolone | Drug | 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 |
|
|
| 12 months |
| Assessment of adverse events | 12 Months |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Feb 12, 2021 | Mar 5, 2021 |
| ID | Term |
|---|---|
| D008181 | Lupus Nephritis |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D008180 | Lupus Erythematosus, Systemic |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D001379 | Azathioprine |
| D008775 | Methylprednisolone |
| D011239 | Prednisolone |
| D013256 | Steroids |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D013872 | Thionucleosides |
| D013457 | Sulfur Compounds |
| D015122 | Mercaptopurine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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