Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease

• Sponsor: Columbia University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01129557
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 46
• Location: 1
• Arms: 3
• Duration (Months): 39
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Proteinuric Kidney Disease; Diabetic Nephropathy; Hypertensive Nephrosclerosis; IgA Nephropathy; Focal Segmental Glomerulosclerosis; Glomerulopathy (Obesity-associated); Glomerulonephritis, Membranous	Drug: Aliskiren; Drug: Valsartan	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Aldosterone Breakthrough During Diovan (Valsartan), Tekturna (Aliskiren), and Combination (Valsartan+Aliskiren) Anti-hypertensive Therapy in Patients With Proteinuric Kidney Disease
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tekturna Tekturna (Aliskiren), a direct renin inhibitor (DRI) 300 mg by mouth once daily for 9 months	Drug: Aliskiren; Other Names: Tekturna
Active Comparator: Diovan Diovan (Valsartan), an angiotensin receptor blocker (ARB) 320 mg by mouth once daily for 9 months	Drug: Valsartan; Other Names: Diovan
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	Drug: Aliskiren; Other Names: Tekturna ; Drug: Valsartan; Other Names: Diovan

Outcome Measures

Primary Outcome Measures

1. Cumulative Incidence of Aldosterone Breakthrough in Subjects Who Completed the 9-month Study Protocol. [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.

Secondary Outcome Measures

1. Serum Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough. [Baseline, 3-, 6-, and 9-months]

   Mean serum aldosterone at baseline, 3-, 6-, and 9-months.

2. Urine Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough. [Baseline, 3-, 6-, and 9-months]

   Mean urine aldosterone at baseline, 3-, 6-, and 9-months.

3. Serum Potassium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough. [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.)

4. Mean 24-hour Urine Sodium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough. [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.)

5. Pre- and Post-treatment Blood Pressure in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

   Compares baseline and final (9 month) blood pressure for subjects with and without aldosterone breakthrough

6. Pre- and Post-treatment Serum Creatinine in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

   Compares baseline and final (9 month) serum creatinine for subjects with and without aldosterone breakthrough

7. Pre- and Post-treatment Serum Potassium in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

   Compares baseline and final (9 month) serum potassium for subjects with and without aldosterone breakthrough

8. Pre- and Post-treatment 24-hour Urine Protein in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

   Compares baseline and final (9 month) 24-hour urine protein for subjects with and without aldosterone breakthrough

9. Pre- and Post-treatment 24-hour Urine Sodium in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

   Compares baseline and final (9 month) 24-hour urine sodium for subjects with and without aldosterone breakthrough

10. Pre- and Post-treatment 24-urine Aldosterone in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

    Compares baseline and final (9 month) 24-hour urine aldosterone for subjects with and without aldosterone breakthrough

11. Pre- and Post-treatment Serum Aldosterone in Subjects With and Without Aldosterone Breakthrough. [Baseline and Final (9 month)]

    Compares baseline and final (9 month) serum aldosterone for subjects with and without aldosterone breakthrough

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Pietro Canetta, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pietro Canetta, MD, Instructor in Clinical Medicine, Nephrology, Columbia University
• ClinicalTrials.gov Identifier: NCT01129557
• Other Study ID Numbers: AAAE0863; #IIRP-906
• First Posted: May 24, 2010
• Last Update Posted: May 15, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Kidney Diseases; Diabetic Nephropathies; Glomerulonephritis, IGA; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Glomerulonephritis, Membranous; Nephrosclerosis; Valsartan

Study Results

Participant Flow

Arm/Group Title	Diovan	Tekturna	Tekturna + Diovan
Arm/Group Description	Diovan (Valsartan), an angiotensin receptor blocker (ARB) 320 mg by mouth once daily for 9 months	Tekturna (Aliskiren), a direct renin inhibitor (DRI) 300 mg by mouth once daily for 9 months	Tekturna (Aliskiren), a direct renin inhibitor (DRI) 150 mg by mouth once daily for 9 months & Diovan (Valsartan), an angiotensin receptor blocker (ARB) 160 mg by mouth once daily for 9 months
Period Title: Overall Study
STARTED	15	17	14
COMPLETED	11	12	10
NOT COMPLETED	4	5	4

Baseline Characteristics

Arm/Group Title	Diovan	Tekturna	Tekturna+Diovan	Total
Arm/Group Description	Diovan (Valsartan), an angiotensin receptor blocker (ARB) 320 mg by mouth once daily for 9 months	Tekturna (Aliskiren), a direct renin inhibitor (DRI) 300 mg by mouth once daily for 9 months	Tekturna (Aliskiren), a direct renin inhibitor (DRI) 150 mg by mouth once daily for 9 months & Diovan (Valsartan), an angiotensin receptor blocker (ARB) 160 mg by mouth once daily for 9 months	Total of all reporting groups
Overall Participants	15	17	14	46
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	17 100%	12 85.7%	44 95.7%
>=65 years	0 0%	0 0%	2 14.3%	2 4.3%
Sex: Female, Male (Count of Participants)
Female	4 26.7%	6 35.3%	4 28.6%	14 30.4%
Male	11 73.3%	11 64.7%	10 71.4%	32 69.6%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 13.3%	3 17.6%	1 7.1%	6 13%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 6.7%	1 5.9%	1 7.1%	3 6.5%
White	8 53.3%	8 47.1%	9 64.3%	25 54.3%
More than one race	4 26.7%	4 23.5%	2 14.3%	10 21.7%
Unknown or Not Reported	0 0%	1 5.9%	1 7.1%	2 4.3%

Outcome Measures

1. Primary Outcome

Title	Cumulative Incidence of Aldosterone Breakthrough in Subjects Who Completed the 9-month Study Protocol.
Description	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.
Time Frame	9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Diovan	Tekturna	Tekturna + Diovan
Arm/Group Description	valsartan [angiotensin receptor blocker (ARB)] : Diovan 320 mg PO once daily for 9 months	aliskiren [direct renin inhibitor (DRI)] : Tekturna 300 mg PO once daily for 9 months	aliskiren + valsartan (DRI + ARB) : Tekturna 150 mg PO once daily + Diovan 160 mg PO once daily for 9 months
Measure Participants	11	12	10
Number [participants]	3 20%	3 17.6%	3 21.4%

2. Secondary Outcome

Title	Serum Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Description	Mean serum aldosterone at baseline, 3-, 6-, and 9-months.
Time Frame	Baseline, 3-, 6-, and 9-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	3 Months: Subjects Without Aldosterone Breakthrough	6 Months: Subjects Without Aldosterone Breakthrough	9 Months: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	3 Months: Subjects With Aldosterone Breakthrough	6 Months: Subjects With Aldosterone Breakthrough	9 Months: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	24	24	9	9	9	9
Mean (Standard Deviation) [ng/dL]	9.1 (5.2)	4.8 (3.1)	4.9 (3.6)	4.9 (3.8)	7.3 (4.5)	8.5 (4.3)	11.7 (5.6)	11.7 (7.5)

3. Secondary Outcome

Title	Urine Aldosterone Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Description	Mean urine aldosterone at baseline, 3-, 6-, and 9-months.
Time Frame	Baseline, 3-, 6-, and 9-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	3 Months: Subjects Without Aldosterone Breakthrough	6 Months: Subjects Without Aldosterone Breakthrough	9 Months: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	3 Months: Subjects With Aldosterone Breakthrough	6 Months: Subjects With Aldosterone Breakthrough	9 Months: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	24	24	9	9	9	9
Mean (Standard Deviation) [ug/day]	10.9 (9.4)	4.4 (3.3)	5.5 (4.3)	4.3 (2.3)	7.4 (4.5)	11.0 (6.2)	14.4 (8.2)	12.8 (5.2)

4. Secondary Outcome

Title	Serum Potassium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Description	Mean serum potassium at baseline, 3-, 6-, and 9-months. (given as reference to interpret contemporaneous plasma & urine aldosterone measurements.)
Time Frame	Baseline, 3-, 6-, and 9-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	3 Months: Subjects Without Aldosterone Breakthrough	6 Months: Subjects Without Aldosterone Breakthrough	9 Months: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	3 Months: Subjects With Aldosterone Breakthrough	6 Months: Subjects With Aldosterone Breakthrough	9 Months: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	24	24	9	9	9	9
Mean (Standard Deviation) [mmol/L]	4.2 (0.5)	4.4 (0.5)	4.4 (0.4)	4.4 (0.4)	4.3 (0.2)	4.2 (0.2)	4.3 (0.2)	4.4 (0.4)

5. Secondary Outcome

Title	Mean 24-hour Urine Sodium Over Time During 9-month Treatment Course in Subjects With and Without Aldosterone Breakthrough.
Description	Mean 24-hour urine sodium (mmol/day) at baseline, 3-, 6-, and 9-months. (given as reference to interpret contemporaneous plasma & urine aldosterone measurements.)
Time Frame	Baseline, 3-, 6-, and 9-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	3 Months: Subjects Without Aldosterone Breakthrough	6 Months: Subjects Without Aldosterone Breakthrough	9 Months: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	3 Months: Subjects With Aldosterone Breakthrough	6 Months: Subjects With Aldosterone Breakthrough	9 Months: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	24	24	9	9	9	9
Mean (Standard Deviation) [mmol/day]	158 (67)	180 (81)	188 (66)	169 (70)	258 (98)	220 (65)	250 (102)	200 (54)

6. Secondary Outcome

Title	Pre- and Post-treatment Blood Pressure in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) blood pressure for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Office systolic Blood Pressure	134.0 (10.9)	122.0 (12.0)	136.3 (9.8)	127.9 (10.8)
Office diastolic Blood Pressure	83.7 (8.9)	74.0 (9.3)	87.7 (6.6)	81.6 (10.2)

7. Secondary Outcome

Title	Pre- and Post-treatment Serum Creatinine in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) serum creatinine for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [mg/dL]	1.2 (0.3)	1.3 (0.4)	1.2 (0.5)	1.4 (1.1)

8. Secondary Outcome

Title	Pre- and Post-treatment Serum Potassium in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) serum potassium for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [(mmol/L)]	4.2 (0.5)	4.4 (0.4)	4.3 (0.2)	4.4 (0.4)

9. Secondary Outcome

Title	Pre- and Post-treatment 24-hour Urine Protein in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) 24-hour urine protein for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [(mg/day)]	2827 (2736)	1911 (2958)	3844 (3502)	2681 (2967)

10. Secondary Outcome

Title	Pre- and Post-treatment 24-hour Urine Sodium in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) 24-hour urine sodium for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [(mmol/day)]	158 (67)	169 (70)	258 (98)	200 (54)

11. Secondary Outcome

Title	Pre- and Post-treatment 24-urine Aldosterone in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) 24-hour urine aldosterone for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [(ug/day)]	10.9 (9.4)	4.3 (2.3)	7.4 (4.5)	12.8 (5.2)

12. Secondary Outcome

Title	Pre- and Post-treatment Serum Aldosterone in Subjects With and Without Aldosterone Breakthrough.
Description	Compares baseline and final (9 month) serum aldosterone for subjects with and without aldosterone breakthrough
Time Frame	Baseline and Final (9 month)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baseline: Subjects Without Aldosterone Breakthrough	Final: Subjects Without Aldosterone Breakthrough	Baseline: Subjects With Aldosterone Breakthrough	Final: Subjects With Aldosterone Breakthrough
Arm/Group Description
Measure Participants	24	24	9	9
Mean (Standard Deviation) [(ng/dL)]	9.1 (5.2)	4.9 (3.8)	7.3 (4.6)	11.7 (7.5)

Adverse Events

Arm/Group Title	Tekturna		Diovan		Tekturna + Diovan
Arm/Group Description	Tekturna (Aliskiren), a direct renin inhibitor (DRI) 300 mg by mouth once daily for 9 months		Diovan (Valsartan), an angiotensin receptor blocker (ARB) 320 mg by mouth once daily for 9 months		Tekturna (Aliskiren), a direct renin inhibitor (DRI) 150 mg by mouth once daily for 9 months & Diovan (Valsartan), an angiotensin receptor blocker (ARB) 160 mg by mouth once daily for 9 months
All Cause Mortality
	Tekturna		Diovan		Tekturna + Diovan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tekturna		Diovan		Tekturna + Diovan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/15 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Tekturna		Diovan		Tekturna + Diovan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/17 (11.8%)		1/15 (6.7%)		2/14 (14.3%)
General disorders
Hypotension	1/17 (5.9%)	1	0/15 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Headache	1/17 (5.9%)	1	0/15 (0%)	0	0/14 (0%)	0
Renal and urinary disorders
>25% increase in creatinine	0/17 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/17 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.