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

March 2, 2017 updated by: Dr. Vir Singh Negi, Jawaharlal Institute of Postgraduate Medical Education & Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

75

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • Pondicherry, India, 605006
        • Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Endoxan
Drug: Azathioprine
azathioprine will be given at 2 mg/kg.
Other Names:
  • 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 Names:
  • 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 Names:
  • Endoxan
Drug: Azathioprine
azathioprine will be given at 2 mg/kg.
Other Names:
  • 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 Names:
  • prednisolone,steroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months
Assessment of adverse events
Time Frame: 12 Months
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

December 30, 2015

First Submitted That Met QC Criteria

December 31, 2015

First Posted (Estimate)

January 1, 2016

Study Record Updates

Last Update Posted (Actual)

March 6, 2017

Last Update Submitted That Met QC Criteria

March 2, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JIP/IEC/SC/2013/5/435

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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