Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
| Status: | Archived |
|---|---|
| Conditions: | Diabetic Neuropathy, High Blood Pressure (Hypertension), Obesity Weight Loss, Renal Impairment / Chronic Kidney Disease, Nephrology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology, Nephrology / Urology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | September 2009 |
| End Date: | December 2012 |
Aldosterone Breakthrough During Diovan (Valsartan), Tekturna (Aliskiren), and Combination (Valsartan+Aliskiren) Anti-hypertensive Therapy in Patients With Proteinuric Kidney Disease
Primary Hypothesis: Aldosterone breakthrough will occur at a far lower frequency during
renin inhibition (0-10% over 9 months), alone or in combination with an ARB, compared to
conventional ARB therapy (35-45% over 9 months). The investigators hypothesize that
aldosterone breakthrough occurs due to accumulation of active precursor substances, most
notably angiotensin II, produced in response to conventional RAAS blockade with
ACEinhibitors and ARBs. The investigators believe that direct renin inhibition (DRI) should
minimize this accumulation and therefore significantly lower or possibly eliminate the
breakthrough effect.
Interruption of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting
enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs), alone and in
combination, has become a leading therapy to slow the progression of chronic heart and
kidney disease. Both types of drugs inhibit the formation of aldosterone, a hormone, which
has been shown to have harmful effects on patients with chronic heart and kidney disorders.
This treatment is effective but not perfect since, even after an initial improvement, many
patients become worse over the long term. This may be due to an unexpected increase in
aldosterone, a phenomenon called "aldosterone breakthrough."
The purpose of this study is to find out whether the use of a direct renin inhibitor (DRI)
alone, or in combination with an angiotensin receptor blocker (ARB), will lessen the
occurrence of aldosterone breakthrough since direct renin inhibitors inhibit the formation
of aldosterone at a very early step. This study will compare the effectiveness of adding
Diovan (valsartan) or Tekturna (aliskiren) or a combination of Diovan and Tekturna to the
usual antihypertensive treatment. The investigators will follow blood pressure, aldosterone
levels, and urinary protein levels over 9 months to evaluate which of these therapies is
most effective for treating hypertension in patients with proteinuric kidney disease.
This is a randomized, open-label, three-arm study comparing Diovan (valsartan, an ARB),
Tekturna (aliskiren, a DRI), and the combination of valsartan + aliskiren (i.e. ARB + DRI).
One hundred twenty subjects (40 per arm) will be treated with Tekturna, Diovan, or a
combination of both drugs for 9 months on top of their usual antihypertensive treatment.
Changes in urinary aldosterone excretion will be monitored during therapy to measure the
incidence of aldosterone breakthrough, defined as any sustained positive change from
baseline urinary aldosterone excretion by the completion of the 9-month study period. This
frequency measure will be compared during ARB, DRI, and ARB + DRI therapy. Changes in
urinary protein excretion will also be monitored alongside the urinary aldosterone levels to
determine whether aldosterone breakthrough is associated with refractory proteinuria. This
is an innovative study that will be the first to (1) examine aldosterone breakthrough during
DRI therapy, and (2) explore whether addition of a DRI to an ARB protects against
aldosterone breakthrough. In addition, this will be the first study to examine whether DRI
therapy (alone or in combination with ARB) is effective therapy for hypertension in patients
with non-diabetic proteinuric kidney disease.
We found this trial at
1
site
Columbia Presbyterian Med Ctr On January 1, 1998, The New York Hospital publicly announced its...
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