Stratified Therapy on Pediatric AAGN - Clinical Trial for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis | NCT05969522

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Primary Purpose

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

GlucoCorticoid

About this trial

This is an interventional treatment trial for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1) Newly diagnosed AAGN patients with onset age of 5-17 years, complete renal biopsy and regular follow-up in the hospital; 2) All enrolled children met the following inclusion criteria: ANCA classification criteria: Patients who meet the 2007 European Medicines Agency (EMA) classification algorithm or the 2012 CHCC definition. Clinical classification includes: micropolyvasculitis (MPA), granulomatous polyvasculitis (GPA) and eosinophilic granulomatous polyvasculitis (EGPA); AAGN diagnostic criteria: ANCA vasculitis combined with any of the following: Hematuria: gross hematuria or microscopic hematuria: 3 times microscopic hematuria within 1 week: red blood cells &gt in urine routine; 3 / high magnification field (HP) or > 17 /ul (higher than normal value, can be adjusted according to the standard of the laboratory of each center); proteinuria: meet any of the following: ① 3 times in 1 week urine routine protein positive; 2) 24h urinary protein quantification > 150 mg or urinary protein/creatinine (mg/mg)> 0.2; 3 urinary microalbumin higher than normal for 3 times in 1 week; Renal insufficiency: increased serum creatinine > 10% base or decreased creatinine clearance > 25%. Exclusion Criteria: - 1) Patients who relied on dialysis for more than 1 month at the time of diagnosis, or the proportion of glomerular sclerosis ≥75% at the time of renal biopsy; 2) Patients with severe infection (such as diffuse peritonitis, severe pneumonia, cellulitis, active Epstein-Barr virus infection, active cytomegalovirus infection, hepatitis B virus infection, tuberculosis infection, fungal infection, etc.) and tumor. 3) Patients with other primary or secondary kidney diseases (such as IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane nephritis, polycystic kidney disease, renal dysplasia, urinary tract malformation, etc.); 4) Parents or children refused to join the group.

Sites / Locations

Children's Hospital of Chongqing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Experimental

Arm Label

Control group-Low and medium risk group

Control group-High risk group

Experimental group-Low and medium risk group

Experimental group-High risk group

Arm Description

The children with AAGN admitted to all cooperating units during 2017.01.01 to 2022.12.31 were followed up for more than 6 months, and the case data were complete. PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Newly diagnosed children with AAGN admitted to our partners during the period of 2023.01.01 to 2023.12.31. All children with AAGN were PARRG risk graded before treatment with RTX and CTX: PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Outcomes

Primary Outcome Measures

Response rate (complete and partial response rate)

The rate of complete or partial response to ANCA vasculitis-associated nephritis (AAGN) was assessed at 6 months. Complete AAGN response was defined as: 1. Estimated glomerular filtration rate (eGFR) ≥60ml/min/1.73m2, or a decrease of less than 15% from baseline eGFR; 2. Proteinuria ≤0.3g/24 hours.Partial AAGN response was defined as: 1. Estimated glomerular filtration rate (eGFR) ≥30ml/min/1.73m2, or a reduction of less than 50% from baseline eGFR; 2. Decreased proteinuria>Baseline 50% or 24-hour urinary protein quantification<50mg/Kg.d.

Secondary Outcome Measures

The time to achieve complete and partial AAGN remission

Full Information

NCT ID

NCT05969522

First Posted

July 10, 2023

Last Updated

July 23, 2023

Sponsor

Wang Mo

1. Study Identification

Unique Protocol Identification Number

NCT05969522

Brief Title

Stratified Therapy on Pediatric AAGN

Acronym

STPARS

Official Title

Stratified Therapy on Pediatric AAGN Based on Risk Assessment-A Prospective, Multicenter, Open, Tendentious Matched Control Clinical Study

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 1, 2023 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Wang Mo

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

Brief Summary

Clinical information of children with ANCA-associated nephritis admitted to Children's Hospital Affiliated to Chongqing Medical University and partner centers from January 1, 2023 to December 31, 2023 was collected: To evaluate and compare the differences in survival, renal outcomes, and adverse reactions in children with ANCA-associated nephritis given different interventions according to the revised PARRG risk stratification, and to evaluate the superiority of ANCA-associated nephritis given according to the revised PARRG risk stratification. (2) To evaluate the efficacy and safety of glucocorticoid combined with rituximab and cyclophosphamide as induction regimen in high-risk group and glucocorticoid combined with rituximab as induction regimen in children with ANCA-associated nephritis (AAGN) in low and middle risk group based on PARRG risk stratification

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, ANCA-Associated Glomerulonephritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Control group-Low and medium risk group

Arm Type

Other

Arm Description

The children with AAGN admitted to all cooperating units during 2017.01.01 to 2022.12.31 were followed up for more than 6 months, and the case data were complete. PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Arm Title

Control group-High risk group

Arm Type

Other

Arm Description

The children with AAGN admitted to all cooperating units during 2017.01.01 to 2022.12.31 were followed up for more than 6 months, and the case data were complete. PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Arm Title

Experimental group-Low and medium risk group

Arm Type

Experimental

Arm Description

Newly diagnosed children with AAGN admitted to our partners during the period of 2023.01.01 to 2023.12.31. All children with AAGN were PARRG risk graded before treatment with RTX and CTX: PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Arm Title

Experimental group-High risk group

Arm Type

Experimental

Arm Description

Newly diagnosed children with AAGN admitted to our partners during the period of 2023.01.01 to 2023.12.31. All children with AAGN were PARRG risk graded before treatment with RTX and CTX: PARRG Classification (pediatric AAGN renal risk grade, pediatric AAV renal risk grade, PARRG) According to the PARRG grading method provided by the Affiliated Children's Hospital of Chongqing Medical University, the enrolled children with AAGN were classified into high risk group, medium risk group, low risk group, medium risk group, low risk combination and low risk group according to the two indexes of eGFR and percentage of glomerular sclerosis during renal biopsy. PARRG risk grading criteria: There are two risk factors for ESRD: (1) eGFR≤20ml/min/1.73m2 at renal biopsy; ② The proportion of glomerular sclerosis ≥30%; High risk resistance: meet 2 risk factors; Moderate risk group: only 1 risk factor; Low risk group: no above risk factors;

Intervention Type

Drug

Intervention Name(s)

GlucoCorticoid

Other Intervention Name(s)

Rituximab, Cyclophosphamide

Intervention Description

The high-risk group: methylprednisolone intravenous 15-30mg/kg/d (Max.500mg/d)*3 days , with 2 courses, interval 5-7 days;Oral prednisone acetate 1.5-2mg/kg/d (Max. 60mg/d) during methylprednisolone impact interval and later stage, with the first reduction after 2-4 weeks. The dose was reduced once every 3 weeks in the first 3 months, and once every 4 weeks in the next 3 months, with a reduction of 5-10mg/ day each time; Rituximab：375 mg/m2/ time, once a week for 4 times;Intravenous cyclophosphamide 7.5-10mg/kg.d*2 days(Max.500mg/d), once every 4 weeks, twice in total, at the 8th and 12th week.The medium-low risk group: methylprednisolone was the same dose as before, but only with 1 course, then followed by oral prednisone acetate 1.5-2mg/kg/d (Max. 60mg/d), divided into three times for 3 weeks, and then changed to morning daily; The dose was reduced as the high-risk group ;Rituximab was the same dose as before.

Primary Outcome Measure Information:

Title

Response rate (complete and partial response rate)

Description

The rate of complete or partial response to ANCA vasculitis-associated nephritis (AAGN) was assessed at 6 months. Complete AAGN response was defined as: 1. Estimated glomerular filtration rate (eGFR) ≥60ml/min/1.73m2, or a decrease of less than 15% from baseline eGFR; 2. Proteinuria ≤0.3g/24 hours.Partial AAGN response was defined as: 1. Estimated glomerular filtration rate (eGFR) ≥30ml/min/1.73m2, or a reduction of less than 50% from baseline eGFR; 2. Decreased proteinuria>Baseline 50% or 24-hour urinary protein quantification<50mg/Kg.d.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

The time to achieve complete and partial AAGN remission

Description

The time to achieve complete and partial AAGN remission

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 1) Newly diagnosed AAGN patients with onset age of 5-17 years, complete renal biopsy and regular follow-up in the hospital; 2) All enrolled children met the following inclusion criteria: ANCA classification criteria: Patients who meet the 2007 European Medicines Agency (EMA) classification algorithm or the 2012 CHCC definition. Clinical classification includes: micropolyvasculitis (MPA), granulomatous polyvasculitis (GPA) and eosinophilic granulomatous polyvasculitis (EGPA); AAGN diagnostic criteria: ANCA vasculitis combined with any of the following: Hematuria: gross hematuria or microscopic hematuria: 3 times microscopic hematuria within 1 week: red blood cells &gt in urine routine; 3 / high magnification field (HP) or > 17 /ul (higher than normal value, can be adjusted according to the standard of the laboratory of each center); proteinuria: meet any of the following: ① 3 times in 1 week urine routine protein positive; 2) 24h urinary protein quantification > 150 mg or urinary protein/creatinine (mg/mg)> 0.2; 3 urinary microalbumin higher than normal for 3 times in 1 week; Renal insufficiency: increased serum creatinine > 10% base or decreased creatinine clearance > 25%. Exclusion Criteria: - 1) Patients who relied on dialysis for more than 1 month at the time of diagnosis, or the proportion of glomerular sclerosis ≥75% at the time of renal biopsy; 2) Patients with severe infection (such as diffuse peritonitis, severe pneumonia, cellulitis, active Epstein-Barr virus infection, active cytomegalovirus infection, hepatitis B virus infection, tuberculosis infection, fungal infection, etc.) and tumor. 3) Patients with other primary or secondary kidney diseases (such as IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane nephritis, polycystic kidney disease, renal dysplasia, urinary tract malformation, etc.); 4) Parents or children refused to join the group.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

cheng Zhong

Phone

15823857537

Email

zhongcheng_cy2018@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

fu g Zhang

Phone

13883058878

Email

zhanggaofu19992004@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

mo Wang

Organizational Affiliation

Children's Hospital of Chongqing Medical University

Official's Role

Study Director

Facility Information:

Facility Name

Children's Hospital of Chongqing Medical University

City

Chongqing

State/Province

Chongqing

ZIP/Postal Code

400015

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

cheng Zhong

Phone

15823857537

Email

zhongcheng_cy2018@163.com

Stratified Therapy on Pediatric AAGN (STPARS)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, ANCA-Associated Glomerulonephritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial