The Effect of Some Drugs Used in Treatment of Vasculitis on the Complement System in Children

NCT03692416 | Unknown Phase 3

• 1 other identifier: ANCA
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Vasculitis denotes affection of small to medium sized vessels by polyangitis. Antineutrophil cytoplasmic antibodies (ANCA) are immunoglobulin G (IgG) autoantibodies directed against constituents of neutrophil granules leading to neutrophil degeneration which results in cell apoptosis known as "Natoptosis" (NaTosis) of the cells. These lead to vessel endothelial cell damage. So that, ANCA formation seems to be the basic reaction in vasculitis. Complement activation at C3 and C4 was thought to be involved in renal damage ANCA associated vasculitis (AAV).

Conditions

Vasculitis

Keywords

C3,C4, C5a & ANCA

Outcome Measures

Primary Outcomes (1)

• The serum levels of C3, C4 & C5a as an indicator of its therapeutic effect.

  An initial estimation as well as follow up estimation after treatment for ANCA, C3, C4 \&C5a levels done, measured By ELISA technique.

  2 years

Study Arms (3)

Ibuprofen

ACTIVE COMPARATOR

Patients in this group will receive: Ibuprofen * Oral * At a dosage of 30 to 40 mg/kg/day, divided into 3 or 4 doses/day, max 2400 mg/day, given with food, in the form of suspension or tablets. * Duration of therapy: 4 - 6 weeks.

Drug: Ibuprofen

Prednisone Oral or Methylprednisolone IV

ACTIVE COMPARATOR

Steroids: 1. Pednisone (for mild/moderate cases): * Oral * Single daily morning dosage of 0.05-2.0 mg/kg/day, or in 2 - 4 divided doses, max 80 mg/d. * Duration: 4 - 6 weeks, with gradual tapering to the lowest effective dose. 2. Methylprednisolone (for severe/acute cases): * IV * 10-30 mg/kg/dose (max 1 g), over 1 hr daily for 1-5 days, followed by oral prednisone, with gradual tapering to the lowest effective dose. * The duration is variable according to the condition of the patient.

Drug: Prednisone

Methotrexate

ACTIVE COMPARATOR

Patients in this group will receive: Methotrexate * Oral * At a dosage of 10 to 20 mg/m2/wk (0.35 to 0.65 mg/kg/wk), max dose 25 mg/wk. * Duration of therapy: 6 - 12 weeks.

Drug: Methotrexate

Interventions

Ibuprofen DRUG

Infants and children with vasculitis attending AssiutU, aged \> 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests \& Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Ibuprofen for ANCA, C3, C4 \&C5a levels done, measured By ELISA technique.

Also known as: Advil

Ibuprofen

Prednisone DRUG

Infants and children with vasculitis attending AssiutU, aged \> 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests \& Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Steroids for ANCA, C3, C4 \&C5a levels done, measured By ELISA technique.

Also known as: Deltasone Oral or Solu-Medrol IV

Prednisone Oral or Methylprednisolone IV

Methotrexate DRUG

Infants and children with vasculitis attending AssiutU, aged \> 1 mo. - 17 yr. of both genders will be included during 2 years of study. Besides full clinical history and thorough examination, all cases will have: CBC, CRP, ESR, Renal function tests \& Albumin / creatinine ratio. All cases will have an initial estimation as well as follow up estimation after treatment by Methotrexate for ANCA, C3, C4 \&C5a levels done, measured By ELISA technique.

Also known as: Rheumatrex

Methotrexate

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants \& children with vasculitis attending Assiut University Child Hospital (AUCH), aged \> 1 mo. - 17yr. of both genders will be included during 2 years of study.

You may not qualify if:

• Those cases aged less than one month will be excluded from the study.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University Pediatric Hospital

Asyut, Upper Egypt, Egypt

Location

Related Publications (8)

• Chen SF, Wang FM, Li ZY, Yu F, Chen M, Zhao MH. The functional activities of complement factor H are impaired in patients with ANCA-positive vasculitis. Clin Immunol. 2017 Feb;175:41-50. doi: 10.1016/j.clim.2016.11.013. Epub 2016 Dec 6.

  PMID: 27939215 BACKGROUND

• Gou SJ, Yuan J, Chen M, Yu F, Zhao MH. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2013 Jan;83(1):129-37. doi: 10.1038/ki.2012.313. Epub 2012 Aug 22.

  PMID: 22913983 BACKGROUND

• Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schonlein purpura). Autoimmun Rev. 2017 Dec;16(12):1246-1253. doi: 10.1016/j.autrev.2017.10.009. Epub 2017 Oct 14.

  PMID: 29037908 BACKGROUND

• Jarrot PA, Kaplanski G. Pathogenesis of ANCA-associated vasculitis: An update. Autoimmun Rev. 2016 Jul;15(7):704-13. doi: 10.1016/j.autrev.2016.03.007. Epub 2016 Mar 9.

  PMID: 26970490 BACKGROUND

• Kallenberg CG, Heeringa P. Complement is crucial in the pathogenesis of ANCA-associated vasculitis. Kidney Int. 2013 Jan;83(1):16-8. doi: 10.1038/ki.2012.371.

  PMID: 23271485 BACKGROUND

• Noone D, Hebert D, Licht C. Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement. Pediatr Nephrol. 2018 Jan;33(1):1-11. doi: 10.1007/s00467-016-3475-5. Epub 2016 Sep 5.

  PMID: 27596099 BACKGROUND

• Pipitone N, Salvarani C. The role of infectious agents in the pathogenesis of vasculitis. Best Pract Res Clin Rheumatol. 2008 Oct;22(5):897-911. doi: 10.1016/j.berh.2008.09.009.

  PMID: 19028370 BACKGROUND

• von Borstel A, Sanders JS, Rutgers A, Stegeman CA, Heeringa P, Abdulahad WH. Cellular immune regulation in the pathogenesis of ANCA-associated vasculitides. Autoimmun Rev. 2018 Apr;17(4):413-421. doi: 10.1016/j.autrev.2017.12.002. Epub 2018 Feb 9.

  PMID: 29428808 BACKGROUND

Related Links

• Nelson Textbook of Pediatrics Expert Consult, Chapter 161, 1-8.
• American College of Rheumatology (ACR) Juvenile Idiopathic Arthritis Guideline Project Plan - June 2017

MeSH Terms

Conditions

Vasculitis

Interventions

Ibuprofen; Prednisone; Methotrexate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Safiea AF El-Deeb, PROF

  Assiut University Child Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No other parties are masked in this clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: The aim of this work is to assess the effect of various forms of treatment of vasculitis on C3, C4, C5a \& ANCA levels in blood, in infants \& children.

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 2, 2018
• Study Start: November 11, 2018
• Primary Completion: November 11, 2021
• Study Completion: May 11, 2022
• Last Updated: February 15, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: starting in January 2021
• Access Criteria: through finding the research in the site of ClinicalTrials.gov

Locations

EG (1)