Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease

Phase 4 Study of the Renoprotective Efficacy of Aliskiren in Addition to Angiotensin II Receptor Blocker in Chronic Kidney Disease

Study objective: To investigate the potential anti-proteinuric and renoprotective efficacy of aliskiren in addition to losartan in patients at risk of developing end-stage renal disease (ESRD)

Methods: This will be a randomized, double-blind study in which proteinuric, non-diabetic patients with chronic kidney disease (CKD) will be assigned in a 1:1 ratio to one of the following treatment groups for 3 years:

• Group A: Losartan (Control arm: conventional treatment)*

• Group B: Aliskiren plus Losartan (Intervention arm)*

  • With optional addition of other anti-hypertensive agents to achieve an optimal target blood pressure of <130/80 mmHg.

Study Overview

• Status: Completed
• Conditions: Kidney Disease
• Intervention / Treatment: Drug: Aliskiren; Drug: Losartan

Detailed Description

Aliskiren is a direct renin inhibitor that has been shown to reduce proteinuria and retard renal deterioration in type 2 diabetic patients with overt nephropathy. However, it is not known if these therapeutic effects can be extended to nondiabetic chronic renal disease. The current study aims to explore this research question by randomly assigning patients with various stages of chronic renal disease to receive either aliskiren on top of losartan, or continuation of losartan.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female 18 - 80 years of age

• Presence of nondiabetic CKD stages 3 to 4 as defined by estimated glomerular filtration rate (eGFR by 4-variable MDRD equation) as follows:

  • Stage 3: Moderate decrease in GFR 30-59 mL/min/1.73 sq.m
  • Stage 4: Severe decrease in GFR 15-29 mL/min/1.73 sq.m
  • CKD is defined as either kidney damage or GFR <60 mL/min/1.73 m2 for > 3 months with variations of less than 30% in the 3 months before screening
• Early-morning urinary protein-to-creatinine ratio of >500 mg/g or 57 mg/mmol on at least 2 occasions four weeks apart
• Patients who are willing to give written, informed consent

Exclusion Criteria:

• eGFR < 15 or > 60 ml/min/1.73m2
• Early-morning urinary protein-to-creatinine ratio of >5000 mg/g or 570 mg/mmol, or urinary protein-to-creatinine ratio of <500 mg/g or 57 mg/mmol
• Serum K+ > 5.2 mmol/L
• Presence of bilateral renal artery stenosis
• Known allergy to losartan or aliskiren
• Patients who are receiving angiotensin II receptor blocker / angiotensin converting enzyme inhibitor combination within 12 weeks of randomization
• Concurrent treatment with corticosteroids, nonsteroidal antiinflammatory drugs, or immunosuppressive agent
• Patients with connective tissue disease or obstructive uropathy
• Patients with concomitant malignancy or any such conditions that will severely limit life expectancy
• Female who are pregnant or intending to conceive
• Female of child-bearing age who are unwilling to practice effective contraception
• Patients who are unable to give informed consent
• Patients simultaneously participating in another study or who have participated in another study within the last 30 days of entry into this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aliskiren	Drug: Aliskiren; For CKD treatment; Other Names: Rasilez
Active Comparator: Losartan; ARB	Drug: Losartan; Control; Other Names: Cozaar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of change in GFR	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in proteinuria	36 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: June 23, 2010
• First Posted (Estimate): June 24, 2010

Study Record Updates

• Last Update Posted (Estimate): July 3, 2015
• Last Update Submitted That Met QC Criteria: July 2, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: proteinuria; CKD; eGFR; Progression of chronic kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: Novartis-ST-02