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Trial record 34 of 146 for:    lupus AND Lupus Nephritis

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

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ClinicalTrials.gov Identifier: NCT02645565
Recruitment Status : Completed
First Posted : January 1, 2016
Last Update Posted : March 6, 2017
Sponsor:
Information provided by (Responsible Party):
Dr. Vir Singh Negi, Jawaharlal Institute of Postgraduate Medical Education & Research

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.

Condition or disease Intervention/treatment Phase
Lupus Nephritis Drug: Cyclophosphamide Drug: Azathioprine Drug: Methylprednisolone Phase 4

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Intravenous Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Proliferative Lupus Nephritis
Study Start Date : December 2015
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


Arm Intervention/treatment
Active Comparator: Low dose Cyclophosphamide
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.
Drug: Cyclophosphamide
Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis.
Other Name: Endoxan

Drug: Azathioprine
azathioprine will be given at 2 mg/kg.
Other Name: Imuran

Drug: 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
Other Name: prednisolone,steroid

Active Comparator: High Dose Cyclophosphamide
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.
Drug: Cyclophosphamide
Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis.
Other Name: Endoxan

Drug: Azathioprine
azathioprine will be given at 2 mg/kg.
Other Name: Imuran

Drug: 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
Other Name: prednisolone,steroid




Primary Outcome Measures :
  1. Assessment of Primary Renal Response [ Time Frame: 12 months ]

    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.


Secondary Outcome Measures :
  1. Proportion of patients with Renal and Non renal disease flares [ Time Frame: 12 months ]
    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.

  2. Assessment of adverse events [ Time Frame: 12 Months ]


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02645565


Locations
India
Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research
Pondicherry, India, 605006
Sponsors and Collaborators
Jawaharlal Institute of Postgraduate Medical Education & Research
Investigators
Principal Investigator: Dr. Vir Singh Negi, DM Jawaharlal Institute of Postgraduate Medical Education & Research
Study Chair: Dr. Sonal Mehra, MD Jawaharlal Institute of Postgraduate Medical Education & Research

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Vir Singh Negi, Head of the department and Proffessor of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research
ClinicalTrials.gov Identifier: NCT02645565     History of Changes
Other Study ID Numbers: JIP/IEC/SC/2013/5/435
First Posted: January 1, 2016    Key Record Dates
Last Update Posted: March 6, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Nephritis
Lupus Nephritis
Lupus Erythematosus, Systemic
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Azathioprine
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones