Stratified Therapy on Pediatric AAGN

NCT ID: NCT05969522

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-31

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control group-Low and medium risk group

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;

Group Type: OTHER

GlucoCorticoid

Intervention Type: DRUG

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.

Control group-High risk group

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;

Group Type: OTHER

GlucoCorticoid

Intervention Type: DRUG

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.

Experimental group-Low and medium risk group

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;

Group Type: EXPERIMENTAL

GlucoCorticoid

Intervention Type: DRUG

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.

Experimental group-High risk group

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;

Group Type: EXPERIMENTAL

GlucoCorticoid

Intervention Type: DRUG

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.

Interventions

GlucoCorticoid

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.

Intervention Type: DRUG

Other Intervention Names

Rituximab; Cyclophosphamide

Eligibility Criteria

Inclusion Criteria

AAGN diagnostic criteria: ANCA vasculitis combined with any of the following:

1. 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);

2. 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;

3. 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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wang Mo

OTHER

Sponsor Role: lead

Responsible Party

Wang Mo

Professor/Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

mo Wang

Role: STUDY_DIRECTOR

Children's Hospital of Chongqing Medical University

Locations

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

cheng Zhong

Role: CONTACT

zhongcheng_cy2018@163.com

15823857537

fu g Zhang

Role: CONTACT

zhanggaofu19992004@163.com

13883058878

Facility Contacts

cheng Zhong

Role: primary

zhongcheng_cy2018@163.com

15823857537

Other Identifiers

ANCA20230706

Identifier Type: -

Identifier Source: org_study_id