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

• ClinicalTrials.gov Identifier: NCT04020328
• Recruitment Status: Unknown
• First Posted: July 16, 2019
• Last Update Posted: February 18, 2020
• Sponsor: Shenzhen Second People's Hospital
• Information provided by (Responsible Party): XUYI, Shenzhen Second People's Hospital

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

Condition or disease	Intervention/treatment	Phase
Glomerulonephritis, IGA; Renal Insufficiency, Chronic	Drug: Leflunomide 20 mg+prednisone 0.5mg/kg/d	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Trial to Evaluate Leflunomide Plus Low Dose Corticosteroid Therapy in Progressive IgA Nephropathy With Renal Insufficiency
• Actual Study Start Date: September 12, 2019
• Estimated Primary Completion Date: March 1, 2022
• Estimated Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: leflunomide + low dose glucocorticoids therapy group; 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; Leflunomide plus low dose glucocorticoids to have the immunosuppressive therapy to those progressive IgA nephropathy with eGFR<50ml/min; Other Name: Arava
No Intervention: Basic conservative treatment group; 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

Outcome Measures

Primary Outcome Measures :

1. renal survival rate [ Time Frame: at least 96 weeks ]
   50% increase in serum creatinine compared with the baseline level or End Stage Renal Disease(ESRD)

Secondary Outcome Measures :

1. proteinuria [ Time Frame: at least 96 weeks ]
   changes in proteinuria compared to the baseline
2. eGFR [ Time Frame: at least 96 weeks ]
   extent of eGFR decline compared with the baseline and annual decline rate
3. complete remission rate [ Time Frame: at least 96 weeks ]
   Complete Remission (CR): proteinuria < 1.0g / 24hr, Scr stable (Scr increase ≤ 15% baseline level)
4. partial remission rate [ Time Frame: at least 96 weeks ]
   Partial Remission (PR): proteinuria in 1.0-3.5g/24hr range and decrease more than 50%, Scr stable (Scr increased ≤ 15% baseline level)
5. no response rate [ Time Frame: at least 96 weeks ]
   No Response (NR)：proteinuria > 3.5g/24hr or decrease less than 50% of baseline , with or without deterioration of renal function

Eligibility Criteria

• Ages Eligible for Study: 14 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Yi Xu; +8613798309505; xuyi20001234@163.com

Contact: QiJun Wan; +8613537857368; yiyuan2224@sina.com

Locations

China, Guangdong

Xu Yi; Recruiting

Shenzhen, Guangdong, China, 518000

Sponsors and Collaborators

Shenzhen Second People's Hospital

More Information

• Responsible Party: XUYI, Principal Investigator, Shenzhen Second People's Hospital
• ClinicalTrials.gov Identifier: NCT04020328
• Other Study ID Numbers: 20193357002
• First Posted: July 16, 2019
• Last Update Posted: February 18, 2020
• Last Verified: February 2020

• 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

Keywords provided by XUYI, Shenzhen Second People's Hospital:

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

Additional relevant MeSH terms:

Renal Insufficiency; Glomerulonephritis; Renal Insufficiency, Chronic; Glomerulonephritis, IGA; Kidney Diseases; Urologic Diseases; Nephritis; Autoimmune Diseases; Immune System Diseases; Prednisone; Leflunomide; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors