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

NCT04020328 | Unknown Phase 4

• 1 other identifier: 20193357002
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Conditions

Glomerulonephritis, IGA; Renal Insufficiency, Chronic

Keywords

Leflunomide; Glucocorticoids; Conservative Treatment; Glomerulonephritis, IGA; Renal Insufficiency, Chronic

Outcome Measures

Primary Outcomes (1)

• renal survival rate

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

  at least 96 weeks

Secondary Outcomes (5)

• proteinuria

  at least 96 weeks

• eGFR

  at least 96 weeks

• complete remission rate

  at least 96 weeks

• partial remission rate

  at least 96 weeks

• no response rate

  at least 96 weeks

Study Arms (2)

leflunomide + low dose glucocorticoids therapy group

EXPERIMENTAL

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

Drug: Leflunomide 20 mg+prednisone 0.5mg/kg/d

Basic conservative treatment group

NO INTERVENTION

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

Interventions

Leflunomide 20 mg+prednisone 0.5mg/kg/d DRUG

Leflunomide plus low dose glucocorticoids to have the immunosuppressive therapy to those progressive IgA nephropathy with eGFR\<50ml/min

Also known as: Arava

leflunomide + low dose glucocorticoids therapy group

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Shenzhen Second People's Hospital: lead

Study Sites (1)

Xu Yi

Shenzhen, Guangdong, 518000, China

RECRUITING

Related Publications (1)

• Alladin A, Hahn D, Hodson EM, Ravani P, Pfister K, Quinn RR, Samuel SM. Immunosuppressive therapy for IgA nephropathy in children. Cochrane Database Syst Rev. 2024 Jun 12;6(6):CD015060. doi: 10.1002/14651858.CD015060.pub2.

  PMID: 38864363 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA; Renal Insufficiency, Chronic

Interventions

Leflunomide; Prednisone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Yi Xu

CONTACT

+8613798309505; xuyi20001234@163.com

QiJun Wan

CONTACT

+8613537857368; yiyuan2224@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: it is a open label trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 16, 2019
• Study Start: September 12, 2019
• Primary Completion: March 1, 2022
• Study Completion: May 31, 2022
• Last Updated: February 18, 2020

Record last verified: 2020-02

Locations

CN (1)