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Leflunomide Plus Low Dose Corticosteroid in Immunoglobulin A (IgA) Nephropathy With Renal Insufficiency

Primary Purpose

Glomerulonephritis, IGA, Renal Insufficiency, Chronic

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Leflunomide 20 mg+prednisone 0.5mg/kg/d
Sponsored by
Shenzhen Second People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glomerulonephritis, IGA focused on measuring Leflunomide, Glucocorticoids, Conservative Treatment, Glomerulonephritis, IGA, Renal Insufficiency, Chronic

Eligibility Criteria

14 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 14 to 65 years old participants, No restrictions on gender or race
  • Diagnosis of primary IgA nephropathy
  • Renal biopsy within 6 months before screening. Renal pathology shows diffuse IgA deposition in the Mesangial area and dense deposition in the Mesangial area under electron microscope. glomeruli more than 8
  • persistent proteinuria ≥ 1 g/24 hr (or urine protein/creatinine ratio ≥ 1.0 mg/g), eGFR at 25-50 ml/min/1.73 m2 (calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)
  • signed written consent; patients under 18 years old need to have legal guardians to sign informed consent at the same time

Exclusion Criteria:

  • Secondary IgA nephropathy (such as lupus nephritis, Henoch-Schönlein purpura, hepatitis B associated glomerulonephritis, hepatitis C associated glomerulonephritis, liver cirrhosis and other autoimmune diseases)
  • eGFR < 25 ml/min/1.73m2 or eGFR > 50 ml/min/1.73m2 (calculated by CKD-EPI formula)
  • Special types of IgA nephropathy need to be excluded, such as crescent IgA glomerulonephritis (defined as the presence of crescents in over 50% of the glomeruli), or minimal lesions with IgA deposition
  • Acute kidney injury within 3 months before screening
  • Received immunosuppressive therapy within 3 months before screening
  • Patients who had acute or chronic infections that need treatment, and the researchers judged that they were not suitable for inclusion in the study
  • Pregnancy, lactation or unreliable birth control
  • Dialysis treatment before screening
  • Allergic or taboo to planned drugs (such as leflunomide, glucocorticoids, etc.)
  • Severe acute or chronic diseases that the researchers believe may bring an excessive risk to the subjects
  • A history of malignant tumors within 5 years, with the exception of carcinoma in situ and papillary thyroid carcinoma which have been adequately treated
  • Participated in other clinical trials and / or used other research drugs within 4 weeks prior to screening

Sites / Locations

  • Xu YiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

leflunomide + low dose glucocorticoids therapy group

Basic conservative treatment group

Arm Description

the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment

the basic conservative treatment group is the delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, RAS inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy

Outcomes

Primary Outcome Measures

renal survival rate
50% increase in serum creatinine compared with the baseline level or End Stage Renal Disease(ESRD)

Secondary Outcome Measures

proteinuria
changes in proteinuria compared to the baseline
eGFR
extent of eGFR decline compared with the baseline and annual decline rate
complete remission rate
Complete Remission (CR): proteinuria < 1.0g / 24hr, Scr stable (Scr increase ≤ 15% baseline level)
partial remission rate
Partial Remission (PR): proteinuria in 1.0-3.5g/24hr range and decrease more than 50%, Scr stable (Scr increased ≤ 15% baseline level)
no response rate
No Response (NR)：proteinuria > 3.5g/24hr or decrease less than 50% of baseline , with or without deterioration of renal function

Full Information

First Posted
July 10, 2019
Last Updated
February 14, 2020
Sponsor
Shenzhen Second People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04020328
Brief Title
Leflunomide Plus Low Dose Corticosteroid in Immunoglobulin A (IgA) Nephropathy With Renal Insufficiency
Official Title
A Randomized, Controlled Trial to Evaluate Leflunomide Plus Low Dose Corticosteroid Therapy in Progressive IgA Nephropathy With Renal Insufficiency
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 12, 2019 (Actual)
Primary Completion Date
March 1, 2022 (Anticipated)
Study Completion Date
May 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shenzhen Second People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
IgA nephropathy is the most common primary glomerulonephritis in the world. Because of the poor treatment effect in advanced patients, it is still the main cause of maintenance dialysis. Current immunosuppressive therapy is still controversial, especially to those progressive IgA nephropathy with eGFR<50ml/min. Leflunomide is widely used in the treatment of rheumatic diseases, such as rheumatoid arthritis and lupus nephritis, it's serum concentration will not be affected by renal function, and it also has antiviral effect. There are two randomized controlled trials and a retrospective study suggesting that leflunomide combined with glucocorticoids can effectively control urinary protein compared with glucocorticoids or conservative treatment, but these three studies are not specifically targeted at patients with estimated Glomerular Filtration Rate(eGFR) < 50ml/min. Investigators will perform a prospective, open-label, randomized, controlled trial to evaluate the efficacy and safety of leflunomide and low dose glucocorticoids therapy in progressive IgA nephropathy with eGFR<50ml/min
Detailed Description
all the participants enrolled in the study will be randomly assigned in a 1:1 ratio, the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment only. Conservative treatment is defined as the treatment of delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, Renin Angiotensin system (RAS) inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy. The course of treatment will last one year, then the leflunomide+glucocorticoids group will continue the conservative treatment. Participants will be follow-up at least 98 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glomerulonephritis, IGA, Renal Insufficiency, Chronic
Keywords
Leflunomide, Glucocorticoids, Conservative Treatment, Glomerulonephritis, IGA, Renal Insufficiency, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
the participants who met the inclusion and exclusion criteria were randomly assigned to leflunomide + low dose glucocorticoids treatment group and conservative treatment group in a 1:1 ratio
Masking
None (Open Label)
Masking Description
it is a open label trial
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
leflunomide + low dose glucocorticoids therapy group
Arm Type
Experimental
Arm Description
the experimental group will receive leflunomide + low dose glucocorticoids therapy on the basis of conservative treatment, while the control group receive conservative treatment
Arm Title
Basic conservative treatment group
Arm Type
No Intervention
Arm Description
the basic conservative treatment group is the delaying the progress of renal function, including low-protein diet supplemented with ketoacid therapy, RAS inhibitor, blood pressure control, lipid-regulating therapy and antiplatelet aggregation therapy
Intervention Type
Drug
Intervention Name(s)
Leflunomide 20 mg+prednisone 0.5mg/kg/d
Other Intervention Name(s)
Arava
Intervention Description
Leflunomide plus low dose glucocorticoids to have the immunosuppressive therapy to those progressive IgA nephropathy with eGFR<50ml/min
Primary Outcome Measure Information:
Title
renal survival rate
Description
50% increase in serum creatinine compared with the baseline level or End Stage Renal Disease(ESRD)
Time Frame
at least 96 weeks
Secondary Outcome Measure Information:
Title
proteinuria
Description
changes in proteinuria compared to the baseline
Time Frame
at least 96 weeks
Title
eGFR
Description
extent of eGFR decline compared with the baseline and annual decline rate
Time Frame
at least 96 weeks
Title
complete remission rate
Description
Complete Remission (CR): proteinuria < 1.0g / 24hr, Scr stable (Scr increase ≤ 15% baseline level)
Time Frame
at least 96 weeks
Title
partial remission rate
Description
Partial Remission (PR): proteinuria in 1.0-3.5g/24hr range and decrease more than 50%, Scr stable (Scr increased ≤ 15% baseline level)
Time Frame
at least 96 weeks
Title
no response rate
Description
No Response (NR)：proteinuria > 3.5g/24hr or decrease less than 50% of baseline , with or without deterioration of renal function
Time Frame
at least 96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 14 to 65 years old participants, No restrictions on gender or race Diagnosis of primary IgA nephropathy Renal biopsy within 6 months before screening. Renal pathology shows diffuse IgA deposition in the Mesangial area and dense deposition in the Mesangial area under electron microscope. glomeruli more than 8 persistent proteinuria ≥ 1 g/24 hr (or urine protein/creatinine ratio ≥ 1.0 mg/g), eGFR at 25-50 ml/min/1.73 m2 (calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) signed written consent; patients under 18 years old need to have legal guardians to sign informed consent at the same time Exclusion Criteria: Secondary IgA nephropathy (such as lupus nephritis, Henoch-Schönlein purpura, hepatitis B associated glomerulonephritis, hepatitis C associated glomerulonephritis, liver cirrhosis and other autoimmune diseases) eGFR < 25 ml/min/1.73m2 or eGFR > 50 ml/min/1.73m2 (calculated by CKD-EPI formula) Special types of IgA nephropathy need to be excluded, such as crescent IgA glomerulonephritis (defined as the presence of crescents in over 50% of the glomeruli), or minimal lesions with IgA deposition Acute kidney injury within 3 months before screening Received immunosuppressive therapy within 3 months before screening Patients who had acute or chronic infections that need treatment, and the researchers judged that they were not suitable for inclusion in the study Pregnancy, lactation or unreliable birth control Dialysis treatment before screening Allergic or taboo to planned drugs (such as leflunomide, glucocorticoids, etc.) Severe acute or chronic diseases that the researchers believe may bring an excessive risk to the subjects A history of malignant tumors within 5 years, with the exception of carcinoma in situ and papillary thyroid carcinoma which have been adequately treated Participated in other clinical trials and / or used other research drugs within 4 weeks prior to screening
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yi Xu
Phone
+8613798309505
Email
xuyi20001234@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
QiJun Wan
Phone
+8613537857368
Email
yiyuan2224@sina.com
Facility Information:
Facility Name
Xu Yi
City
Shenzhen
State/Province
Guangdong
ZIP/Postal Code
518000
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

Leflunomide Plus Low Dose Corticosteroid in Immunoglobulin A (IgA) Nephropathy With Renal Insufficiency

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