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

NCT02645565 | Completed Phase 4

• 1 other identifier: JIP/IEC/SC/2013/5/435
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (2)

• Proportion of patients with Renal and Non renal disease flares

  12 months

• Assessment of adverse events

  12 Months

Study Arms (2)

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.

Drug: Cyclophosphamide; Drug: Azathioprine; Drug: Methylprednisolone

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.

Drug: Cyclophosphamide; Drug: Azathioprine; Drug: Methylprednisolone

Interventions

Cyclophosphamide DRUG

Cyclophosphamide is an alkylating agent used for the treatment of lupus nephritis.

Also known as: Endoxan

High Dose Cyclophosphamide; Low dose Cyclophosphamide

Azathioprine DRUG

azathioprine will be given at 2 mg/kg.

Also known as: Imuran

High Dose Cyclophosphamide; Low dose Cyclophosphamide

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

Also known as: prednisolone,steroid

High Dose Cyclophosphamide; Low dose Cyclophosphamide

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of SLE according to the American College of Rheumatology (ACR) criteria
• Age \>16 years
• Proteinuria ≥500 mg in 24 hours/ urine routine microscopy showing active cellular casts/sediments.
• Biopsy-proven proliferative lupus glomerulonephritis of class III, IV according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.

You may not qualify if:

• Patients ever treated previously with intravenous or oral cyclophosphamide or received steroids \>15mg/day in the last 3 months.
• Patients with renal thrombotic microangiopathy, preexisting chronic renal failure, pregnancy, previous malignancy (except skin and cervical intraepithelial neoplasia), diabetes mellitus or coronary heart disease.
• Patients with previously documented severe toxicity to immunosuppressive drugs.
• Patients with acute/chronic infections.
• Pregnancy

Sponsors & Collaborators

• Jawaharlal Institute of Postgraduate Medical Education & Research: lead

Study Sites (1)

Department of Clinical Immunology , Jawaharlal Institute of Post graduate Medical Educationa and Research

Puducherry, Puducherry, 605006, India

Location

Related Publications (1)

• 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.

  PMID: 29450636 DERIVED

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Cyclophosphamide; Azathioprine; Methylprednisolone; Prednisolone; Steroids

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the department and Proffessor of Clinical Immunology

Study Record Dates

• First Submitted: December 30, 2015
• First Posted: January 1, 2016
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 6, 2017

Record last verified: 2017-03

Locations

IN (1)