Low-dose VS High-dose IV Cyclophosphamide for Proliferative LN in Children

NCT01861561 | Terminated Phase 4 DMC

• 1 other identifier: 125/2556(EC2)
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Proliferative lupus nephritis (LN)is the predominant cause of morbidity and mortality in juvenile Systemic Lupus Erythematosus (SLE). Induction therapy with high-dose intravenous cyclophosphamide can improve renal outcomes, but considerably associated with infection. Although severe infection is the significant complication related to poorer prognosis for juvenile SLE patients in Asia, cyclophosphamide is still commonly used as the drug of choice for severe lupus nephritis. Euro-Lupus Nephritis Trial demonstrated low-dose intravenous cyclophosphamide regimen followed by azathioprine achieved good clinical results comparable with obtained high-dose regimen. There was lower number of severe infection episodes, but no significant difference. Recent studies applied low dose of cyclophosphamide (500 mg/m2/dose or 500 mg/dose)in young patients and showed good renal response. Low-dose intravenous cyclophosphamide regimen might promote non-inferior renal remission whereas decrease risk of serious infection and improve overall patient outcomes.

Conditions

Renal Insufficiency; Infection

Outcome Measures

Primary Outcomes (1)

• renal response

  3 main renal parameters: renal function(eCCl),proteinuria(spot urine protein/creatinine ratio, UPCR), and urine sediment (rbc,wbc,and casts) 'renal remission' * complete- normal renal function, UPCR\<0.2, and normal urine sediment(rbc\<5,wbc\<5/HPF,and no cast) * partial- at least 50%improvement in 2 main parameters with UPCR \<= 1.0 and without worsening of remaining main parameter

  at 6 months of the treatment

Secondary Outcomes (1)

• infection

  within 6 months

Other Outcomes (2)

• Patient well being

  at 0,1,3 and 6 months of the treatment

• SLE disease activity index score

  at 0,1,3 and 6 months of the treatment

Study Arms (2)

Low-dose intravenous cyclophosphamide

EXPERIMENTAL

Low-dose intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months for 7 doses. Total duration is 6 months for the induction treatment.

Drug: Low-dose intravenous cyclophosphamide

High-dose intravenous cyclophosphamide

ACTIVE COMPARATOR

High-dose intravenous cyclophosphamide 1,000 mg/m2/dose, the first dose will be started with 500 mg/m2/dose and steped up to 750 mg/m2/dose for the second dose. Then the dosage will be increased to 1,000 mg/m2/dose for the third dose and continued the dosage through the seventh dose. Total duration is 6 months for the induction treatment.

Drug: High-dose intravenous cyclophosphamide

Interventions

Low-dose intravenous cyclophosphamide DRUG

Intravenous cyclophosphamide 500 mg/m2/dose every 4 weeks/months, total 7 doses

Also known as: Cytoxan

Low-dose intravenous cyclophosphamide

High-dose intravenous cyclophosphamide DRUG

Intravenous cyclophosphamide every 4 weeks/months, total in 7 doses: the 1st dose-500 mg/m2/dose,the 2nd dose-750 mg/m2/dose, the 3rd-7th doses- 1,000 mg/m2/dose with the maximum dose at 1,500 mg/dose

Also known as: Cytoxan

High-dose intravenous cyclophosphamide

Eligibility Criteria

• Age: Up to 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Child up to 15 years of age who fulfilled the 1997 updating the American College of Rheumatology revised criteria for the classification of SLE and his or her renal biopsy reveals lupus nephritis class III or IV regarding to International Society of Nephrology/Renal Pathology Society revision on the classification of the lupus nephritis.

You may not qualify if:

• patient who has prior renal insufficiency due to chronic kidney disease other than lupus nephritis
• patient who has the history of cyclophosphamide hypersensitivity
• patient who has prior cyclophosphamide or mycophenolate mofetil administration within 6 months
• patient who is pregnant

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Nephrology division, Department of Pediatrics, Siriraj Hospital

Bangkoknoi, Bangkok, 10700, Thailand

Location

MeSH Terms

Conditions

Renal Insufficiency; Infections

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Nuntawan Piyaphanee, MD

  Siriraj Hospital

  PRINCIPAL INVESTIGATOR

• Anirut Pattaragarn, MD

  Siriraj Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2013
• First Posted: May 23, 2013
• Study Start: May 1, 2013
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: September 4, 2020

Record last verified: 2020-09

Locations

TH (1)