Aliskiren for Immunoglobulin A (IgA) Nephropathy

The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study

Immunoglobulin A (IgA) nephropathy is the most common type of primary glomerulonephritis in the world. Current treatment with angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) is not entirely effective. Aliskiren, a direct renin inhibitor, acts on the rate limiting step of the renin-angiotensin axis. In addition to lowering the blood pressure, recent study in diabetic nephropathy suggests an independent anti-proteinuric effect. The investigators plan to conduct a randomized placebo-control cross-over study to evaluate the safety and efficacy of aliskiren in the treatment of IgA nephropathy. The investigators plan to recruit 57 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite conventional therapy. They will be randomized to aliskiren for 16 weeks or no treatment, followed by cross over to the other arm after a washout period. Proteinuria, albuminuria, renal function, serum and urinary markers will be quantified. This study will explore the potential anti-proteinuric effect of aliskiren in the treatment of IgA nephropathy, which has no specific treatment at present.

Study Overview

• Status: Completed
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: Aliskiren; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 18-65 years
• requires anti-hypertensive therapy
• renal biopsy within the past 3 years and confirmed the diagnosis of IgA nephropathy
• proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 3 consecutive samples within 12 weeks despite ACE inhibitor or ARB treatment for at least 3 months
• estimated glomerular filtration rate > 30 ml/min/1.73m2
• willingness to give written consent and comply with the study protocol

Exclusion Criteria:

• Patients who are diabetic, and patients with systemic diseases that may cause IgA nephropathy or another nephropathy.
• Pregnancy, lactating or childbearing potential without effective method of birth control
• Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication
• History of malignancy, including leukemia and lymphoma within the past 2 years
• Systemic infection requiring therapy at study entry
• Any other severe coexisting disease such as, but not limited to, chronic liver disease, myocardial infarction, cerebrovascular accident, malignant hypertension
• History of drug or alcohol abuse within past 2 years
• Participation in any previous trial on aliskiren or other renin inhibitor
• Previous treatment with fish oil, steroid, cytotoxic agents, or aldosterone antagonist
• History of treatment with other drugs that may affect proteinuria within past 2 years
• Patients receiving treatment of corticosteroid
• On other investigational drugs within last 30 days
• History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study
• History of non-compliance
• Known history of sensitivity or allergy to aliskiren or other renin inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I; each subject will receive oral aliskiren 300 mg/day for 16 weeks, followed by a washout period of 4 weeks, then crossed over to placebo for another 16 weeks	Drug: Aliskiren; Aliskiren 300 mg daily oral; Drug: Placebo; starch tablet, 300 mg/day
Active Comparator: II; each subject will receive placebo for 16 weeks, followed by a washout period of 4 weeks, then crossed over to oral aliskiren 300 mg/day for another 16 weeks	Drug: Aliskiren; Aliskiren 300 mg daily oral; Drug: Placebo; starch tablet, 300 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change in the degree of proteinuria	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
rate of decline of estimated GFR	16 weeks
change in serum and urinary inflammatory markers	16 weeks

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Publications and helpful links

General Publications

• Szeto CC, Kwan BC, Chow KM, Leung CB, Li PK. The safety and short-term efficacy of aliskiren in the treatment of immunoglobulin a nephropathy--a randomized cross-over study. PLoS One. 2013 May 10;8(5):e62736. doi: 10.1371/journal.pone.0062736. Print 2013.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 26, 2009
• First Posted (Estimate): March 27, 2009

Study Record Updates

• Last Update Posted (Estimate): December 4, 2012
• Last Update Submitted That Met QC Criteria: December 3, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: proteinuria; renal failure; glomerulonephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: AIgA