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

Sponsor

The University of Hong Kong (Other)

Overall Status

Completed

CT.gov ID

NCT01150201

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Disease	Drug: Aliskiren Drug: Losartan	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Aliskiren

Aliskiren

Drug: Aliskiren

For CKD treatment

Other Names:

Rasilez

Active Comparator: Losartan

ARB

Drug: Losartan

Control

Other Names:

Cozaar

Outcome Measures

Primary Outcome Measures

Rate of change in GFR [36 months]

Secondary Outcome Measures

Change in proteinuria [36 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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