Efficacy and Safety of Aliskiren 75 mg, 150 mg, and 300 mg in Elderly Patients With Essential Hypertension When Given With a Light Meal in a 8 Week Placebo-controlled Study

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00706134
• Collaborator: (none)
• Enrollment: 756
• Locations: 8
• Arms: 4
• Duration (Months): 11
• Patients Per Site: 94.5
• Patients Per Site Per Month: 8.6

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of aliskiren 75 mg, 150 mg, and 300 mg in elderly patients with essential hypertension when given with a light meal.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Placebo; Drug: Aliskiren 75 mg; Drug: Aliskiren 150 mg; Drug: Aliskiren 300 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 756 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Eight-week Double-blind, Multi-center, Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Aliskiren 75 mg, 150 mg, and 300 mg in Elderly Patients With Essential Hypertension When Given With a Light Meal
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablet taken once daily in the morning with a light meal.
Experimental: Aliskiren 75 mg	Drug: Aliskiren 75 mg; Aliskiren 75 mg tablet taken once daily in the morning with a light meal.
Experimental: Aliskiren 150 mg	Drug: Aliskiren 150 mg; Aliskiren 150 mg tablet taken once daily in the morning with a light meal.
Experimental: Aliskiren 300 mg	Drug: Aliskiren 300 mg; Aliskiren 300 mg tablet taken once daily in the morning with a light meal.

Outcome Measures

Primary Outcome Measures

1. Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8) [Baseline to end of study (Week 8)]

Secondary Outcome Measures

1. Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) [Baseline to end of study (Week 8)]

2. Percentage of Patients Achieving Systolic Blood Pressure Response [Baseline to end of study (Week 8)]

   Patients achieving a systolic blood pressure response had to have a msSBP < 140 mmHg at the end of the study and/or a ≥ 20 mmHg reduction in msSBP from baseline to the end of the study.

3. Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study [Baseline to end of study (Week 8)]

   Two 24-hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline and one at the end of the study. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient.

4. Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) [Baseline to end of study (Week 8)]

   Smoothness index (SI) is a measure of consistency of the BP reduction over 24 hours. The SI was obtained by first calculating the mean blood pressure value at each hour of the 24-hour ambulatory blood pressure monitoring period, both before and during treatment. Similarly, the change from baseline in blood pressure was calculated at each hour. The average hourly change from baseline (δh) and standard deviation (std δh) of the hourly changes were computed, and the SI was derived: SI = δh/std δh. A negative change score indicates improvement.

5. Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8) [Baseline to end of study (week 8)]

   The morning surge was defined as the average of the hourly means in the last three hours (hours 22, 23, 24) of the 24 hour ambulatory blood pressure monitoring assessment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female outpatients 65 years of age and older.

• Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent).

• At the randomization visit patients must have an office msSBP greater than or equal to 150 mmHg and < 180 mmHg (msDBP <110 mmHg) with a less than or equal to 15 mmHg difference during the last two visits of the single blind run-in period.

Exclusion Criteria:

• Severe hypertension [Office msDBP ≥110 mmHg and/or mean sitting systolic blood pressure (msSBP) ≥ 180 mmHg].

• History or evidence of a secondary form of hypertension.

• Known Keith-Wagener grade III or IV hypertensive retinopathy.

• History of hypertensive encephalopathy or cerebrovascular accident, including a history of transient ischemic cerebral attack (TIA).

• Current diagnosis of heart failure (NYHA Class II-IV).

• History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).

• Current angina pectoris requiring pharmacological therapy other than nitrates.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Buenos Aires		Argentina
2	Investigative Site	Prague		Czech Republic
3	Investigative Site	Berlin		Germany
4	Investigative Site	Reykjavik		Iceland
5	Investigative Site	Rome		Italy
6	Investigative Site	Amsterdam		Netherlands
7	Investigative Site	Warsaw		Poland
8	Investigative Site	Bratislava		Slovakia

Sponsors and Collaborators

• Novartis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00706134
• Other Study ID Numbers: CSPP100A2405
• First Posted: Jun 27, 2008
• Last Update Posted: Jun 28, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: Hypertension; ≥ 65 years; aliskiren; placebo; light meal
• Additional relevant MeSH terms: Hypertension; Essential Hypertension

Study Results

Participant Flow

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Period Title: Overall Study
STARTED	189	192	189	186
Entered Double-blind Period	187	192	189	186
COMPLETED	169	173	183	175
NOT COMPLETED	20	19	6	11

Baseline Characteristics

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg	Total
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.	Total of all reporting groups
Overall Participants	189	192	189	186	756
Age, Customized (Number) [Number]
≥ 65 and < 75 years of age	128 67.7%	131 68.2%	129 68.3%	129 69.4%	517 68.4%
≥ 75 years of age	61 32.3%	61 31.8%	60 31.7%	57 30.6%	239 31.6%
Sex: Female, Male (Count of Participants)
Female	100 52.9%	109 56.8%	106 56.1%	102 54.8%	417 55.2%
Male	89 47.1%	83 43.2%	83 43.9%	84 45.2%	339 44.8%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP)From Baseline to End of Study (Week 8)
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	184	192	188	186
Least Squares Mean (Standard Error) [mmHg]	-7.97 (1.043)	-12.51 (1.024)	-15.28 (1.035)	-14.14 (1.042)

2. Secondary Outcome

Title	Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	184	192	188	186
Least Squares Mean (Standard Error) [mmHg]	-3.50 (0.579)	-5.33 (0.568)	-6.42 (0.575)	-6.66 (0.579)

3. Secondary Outcome

Title	Percentage of Patients Achieving Systolic Blood Pressure Response
Description	Patients achieving a systolic blood pressure response had to have a msSBP < 140 mmHg at the end of the study and/or a ≥ 20 mmHg reduction in msSBP from baseline to the end of the study.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) - All randomized patients. Two randomized patients who did not meet study criteria were excluded from the FAS.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	184	192	188	186
Number [Percentage of participants]	28.8 15.2%	42.4 22.1%	44.1 23.3%	47.3 25.4%

4. Secondary Outcome

Title	Change in Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study
Description	Two 24-hour ambulatory blood pressure monitoring (ABPM) evaluations were performed, one at baseline and one at the end of the study. For each evaluation, the ABPM device was attached to the non-dominant arm of the patient.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	50	64	70	58
Ambulatory Systolic Blood Pressure	-1.15 (1.280)	-3.33 (1.155)	-5.76 (1.128)	-5.83 (1.520)
Ambulatory Diastolic Blood Pressure	0.31 (0.990)	-1.78 (0.877)	-3.26 (0.693)	-2.45 (0.823)

5. Secondary Outcome

Title	Change in the Smoothness Index (SI) of the Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8)
Description	Smoothness index (SI) is a measure of consistency of the BP reduction over 24 hours. The SI was obtained by first calculating the mean blood pressure value at each hour of the 24-hour ambulatory blood pressure monitoring period, both before and during treatment. Similarly, the change from baseline in blood pressure was calculated at each hour. The average hourly change from baseline (δh) and standard deviation (std δh) of the hourly changes were computed, and the SI was derived: SI = δh/std δh. A negative change score indicates improvement.
Time Frame	Baseline to end of study (Week 8)

Outcome Measure Data

Analysis Population Description

Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	50	64	70	58
Least Squares Mean (Standard Error) [Ratio]	-0.11 (0.102)	-0.38 (0.092)	-0.50 (0.089)	-0.51 (0.096)

6. Secondary Outcome

Title	Change in Morning Surge of Ambulatory Systolic Blood Pressure From Baseline to End of Study (Week 8)
Description	The morning surge was defined as the average of the hourly means in the last three hours (hours 22, 23, 24) of the 24 hour ambulatory blood pressure monitoring assessment period.
Time Frame	Baseline to end of study (week 8)

Outcome Measure Data

Analysis Population Description

Ambulatory blood pressure monitoring completers population: All patients that completed both ambulatory blood pressure monitoring assessments successfully.

Arm/Group Title	Placebo	Aliskiren 75 mg	Aliskiren 150 mg	Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.	Aliskiren 75 mg tablet taken once daily in the morning with a light meal.	Aliskiren 150 mg tablet taken once daily in the morning with a light meal.	Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
Measure Participants	50	64	70	58
Least Squares Mean (Standard Error) [mmHg]	0.46 (1.782)	-3.04 (1.596)	-7.03 (1.539)	-3.96 (1.660)

Adverse Events

Time Frame	End of study (week 8)
Adverse Event Reporting Description	Population description of safety set.
Arm/Group Title	Placebo		Aliskiren 75 mg		Aliskiren 150 mg		Aliskiren 300 mg
Arm/Group Description	Placebo tablet taken once daily in the morning with a light meal.		Aliskiren 75 mg tablet taken once daily in the morning with a light meal.		Aliskiren 150 mg tablet taken once daily in the morning with a light meal.		Aliskiren 300 mg tablet taken once daily in the morning with a light meal.
All Cause Mortality
	Placebo		Aliskiren 75 mg		Aliskiren 150 mg		Aliskiren 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Aliskiren 75 mg		Aliskiren 150 mg		Aliskiren 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/186 (0.5%)		2/191 (1%)		3/189 (1.6%)		0/188 (0%)
Ear and labyrinth disorders
Vertigo	1/186 (0.5%)		0/191 (0%)		0/189 (0%)		0/188 (0%)
Eye disorders
Glaucoma	0/186 (0%)		0/191 (0%)		1/189 (0.5%)		0/188 (0%)
Gastrointestinal disorders
Haemorrhoidal haemorrhage	0/186 (0%)		0/191 (0%)		1/189 (0.5%)		0/188 (0%)
Infections and infestations
Erysipelas	0/186 (0%)		1/191 (0.5%)		0/189 (0%)		0/188 (0%)
Injury, poisoning and procedural complications
Concussion	1/186 (0.5%)		0/191 (0%)		0/189 (0%)		0/188 (0%)
Contusion	1/186 (0.5%)		0/191 (0%)		0/189 (0%)		0/188 (0%)
Wrist fracture	1/186 (0.5%)		0/191 (0%)		0/189 (0%)		0/188 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/186 (0%)		1/191 (0.5%)		0/189 (0%)		0/188 (0%)
Nervous system disorders
Haemorrhagic stroke	0/186 (0%)		0/191 (0%)		1/189 (0.5%)		0/188 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Aliskiren 75 mg		Aliskiren 150 mg		Aliskiren 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/186 (0%)		0/191 (0%)		0/189 (0%)		0/188 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.