- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01129557
Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Proteinuria > 300 mg/day
- Normal to mildly reduced kidney function (eGFR > 45 ml/min/1.73m2)
- Systolic blood pressure >130 mm Hg
- Diastolic blood pressure >70 mm Hg
- Diagnoses of diabetic nephropathy, hypertensive nephrosclerosis, IgA nephropathy, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, membranous nephropathy, fibrillary glomerulonephritis, or obesity-associated glomerulopathy
Exclusion Criteria:
- Concomitant use of cyclosporine (which can interact with aliskiren)
- Inability to undergo 6 week washout period if already on RAAS-blocking drug(s) (includes renin inhibitor, ACE-inhibitor, ARB, and mineralocorticoid receptor blocker)
- eGFR < 45 ml/min/1.73m2
- Urine protein excretion < 300 mg/day
- Serum K > 5.0 mEq/l
- Systolic blood pressure > 170 mm Hg or < 130 mm Hg after washout period
- Diastolic blood pressure > 110 mm Hg or < 70 mm Hg after washout period
- Congestive heart failure NYHA class III and IV
- History of any cardiovascular events (stroke, TIA, MI, unstable angina, CABG, PCI, CHF hospitalization) in 3 months prior to study visit 1
- 2nd or 3rd degree heart block without a pacemaker or other uncontrolled arrhythmia
- Clinically significant valvular disease
- Known renal artery stenosis
- Any surgical or medical condition that might significantly alter the pharmacokinetics of the study drugs (n.b. bariatric surgery > 6 months prior to visit 1 is not an exclusion)
- History or evidence of drug or alcohol abuse within the last 12 months
- Any concurrent life threatening condition with a life expectancy less than 2 years
- Pregnant or nursing (lactating) women
- Women of child-bearing potential unless postmenopausal for at least 1 year, surgically sterile, or using effective methods of contraception as defined by local health authorities
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Tekturna
Tekturna (Aliskiren), a direct renin inhibitor (DRI) 300 mg by mouth once daily for 9 months
|
Other Names:
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Active Comparator: Diovan
Diovan (Valsartan), an angiotensin receptor blocker (ARB) 320 mg by mouth once daily for 9 months
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Other Names:
|
Active Comparator: Tekturna & Diovan
Tekturna (Aliskiren), a direct renin inhibitor (DRI) 150 mg by mouth once daily & Diovan (Valsartan), an angiotensin receptor (ARB) 160 mg by mouth once daily for 9 months
|
Other Names:
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative Incidence of Aldosterone Breakthrough in Subjects Who Completed the 9-month Study Protocol.
Time Frame: 9 months
|
The primary outcome of this study is the 9-month cumulative incidence of aldosterone breakthrough, defined as a sustained increase in 24-hour urine aldosterone above baseline, in each treatment arm.
|
9 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline, 3-, 6-, and 9-months
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Mean serum aldosterone at baseline, 3-, 6-, and 9-months.
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Baseline, 3-, 6-, and 9-months
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Urine Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline, 3-, 6-, and 9-months
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Mean urine aldosterone at baseline, 3-, 6-, and 9-months.
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Baseline, 3-, 6-, and 9-months
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Serum Potassium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline, 3-, 6-, and 9-months
|
Mean serum potassium at baseline, 3-, 6-, and 9-months.
(given as reference to interpret contemporaneous plasma & urine aldosterone measurements.)
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Baseline, 3-, 6-, and 9-months
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Mean 24-hour Urine Sodium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline, 3-, 6-, and 9-months
|
Mean 24-hour urine sodium (mmol/day) at baseline, 3-, 6-, and 9-months.
(given as reference to interpret contemporaneous plasma & urine aldosterone measurements.)
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Baseline, 3-, 6-, and 9-months
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Pre- and Post-treatment Blood Pressure in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
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Compares baseline and final (9 month) blood pressure for subjects with and without aldosterone breakthrough
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Baseline and Final (9 month)
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Pre- and Post-treatment Serum Creatinine in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
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Compares baseline and final (9 month) serum creatinine for subjects with and without aldosterone breakthrough
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Baseline and Final (9 month)
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Pre- and Post-treatment Serum Potassium in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
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Compares baseline and final (9 month) serum potassium for subjects with and without aldosterone breakthrough
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Baseline and Final (9 month)
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Pre- and Post-treatment 24-hour Urine Protein in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
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Compares baseline and final (9 month) 24-hour urine protein for subjects with and without aldosterone breakthrough
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Baseline and Final (9 month)
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Pre- and Post-treatment 24-hour Urine Sodium in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
|
Compares baseline and final (9 month) 24-hour urine sodium for subjects with and without aldosterone breakthrough
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Baseline and Final (9 month)
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Pre- and Post-treatment 24-urine Aldosterone in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
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Compares baseline and final (9 month) 24-hour urine aldosterone for subjects with and without aldosterone breakthrough
|
Baseline and Final (9 month)
|
Pre- and Post-treatment Serum Aldosterone in Subjects With and Without Aldosterone Breakthrough.
Time Frame: Baseline and Final (9 month)
|
Compares baseline and final (9 month) serum aldosterone for subjects with and without aldosterone breakthrough
|
Baseline and Final (9 month)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Pietro Canetta, MD, Columbia University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Urologic Diseases
- Endocrine System Diseases
- Diabetes Complications
- Diabetes Mellitus
- Nephritis
- Kidney Diseases
- Diabetic Nephropathies
- Glomerulonephritis
- Glomerulosclerosis, Focal Segmental
- Glomerulonephritis, IGA
- Nephrosclerosis
- Glomerulonephritis, Membranous
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Valsartan
Other Study ID Numbers
- AAAE0863
- #IIRP-906 (Other Identifier: Novartis)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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