ACTION: Blood Pressure Lowering of Aliskiren HCTZ Compared to HCTZ in Stage 2 Systolic Hypertension in Older Population

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00760266
• Collaborator: (none)
• Enrollment: 451
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 64.8

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of initial use of a fixed dose combination of aliskiren Hydrochlorothiazide (HCTZ) compared to Hydrochlorothiazide in older population with Stage 2 systolic hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren; Drug: Hydrochlorothiazide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 451 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: An 8-week Randomized, Double-blind, Parallel-group, Multi-center, Active-controlled Dose Escalation Study to Evaluate the Efficacy and Safety of Aliskiren HCTZ (300/25 mg) Compared to HCTZ (25 mg) in Older Patients With Stage 2 Systolic Hypertension
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren/HCTZ 300/25 mg	Drug: Aliskiren; Aliskiren 150 mg for 1 week, Aliskiren 300 mg (with or without amlodipine)for 7 weeks
Active Comparator: HCTZ 25 mg	Drug: Hydrochlorothiazide; Hydrochlorothiazide (HCTZ) 12.5 mg for week 1; Hydrochlorothiazide (HCTZ) 25 mg (with or without amlodipine)for 7 weeks

Outcome Measures

Primary Outcome Measures

1. Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4 [Baseline and Week 4]

Secondary Outcome Measures

1. Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4 [Baseline and Week 4]

2. Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8 [Baseline and Week 8]

3. Percentage of Responders at Week 4 and Week 8 [At 4 weeks and 8 weeks]

   Responders defined as mean sitting Systolic Blood Pressure < 140 mmHg or reduction of ≥ 20 mmHg from baseline

4. Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8 [At Weeks 4 and 8]

   Blood pressure control defined as mean sitting Systolic Blood Pressure < 140 mm Hg and mean sitting Diastolic Blood Pressure < 90 mm Hg

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female outpatients, ≥ 55 years old

2. Patients with essential hypertension

3. Prior to randomization: Patients must have an office cuff mean sitting Systolic Blood Pressure ≥ 160 mm Hg and < 200 mm Hg

4. Patients who are eligible and able to participate in the study, and who are willing to give informed consent before any assessment is performed

Exclusion Criteria:

1. Office blood pressure measured by cuff (msSBP ≥ 200 mm Hg and/or msDBP ≥ 110 mm Hg) at Visits 1-5

2. History or evidence of a secondary hypertension of any etiology (e.g., uncorrected renal artery stenosis, pheochromocytoma).

3. History of hypertensive encephalopathy or heart failure (New York Heart Association [NYHA] Class II-IV)

4. Cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 1 year prior to Visit 1

5. Serum sodium less than the lower limit of normal, serum potassium < 3.5 mEq/L (corresponding to 3.5 mmol/L) or ≥ 5.3 mEq/L (corresponding to 5.3 mmol/L), or dehydration at Visit 1.

6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)

7. Use of other investigational drugs within 30 days of enrollment.

Other exclusions may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sites in USA	East Hanover	New Jersey	United States	07936

Sponsors and Collaborators

• Novartis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00760266
• Other Study ID Numbers: CSPP100A2411
• First Posted: Sep 26, 2008
• Last Update Posted: Apr 4, 2011
• Last Verified: Mar 1, 2011

• Keywords provided by , ,: Hypertension; older population; aliskiren; hydrochlorothiazide; systolic blood pressure; diastolic blood pressure; amlodipine, stage 2
• Additional relevant MeSH terms: Hypertension; Systolic Murmurs; Hydrochlorothiazide

Study Results

Participant Flow

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Period Title: Overall Study
STARTED	228	223
COMPLETED	204	205
NOT COMPLETED	24	18

Baseline Characteristics

Arm/Group Title	Aliskiren/HCTZ	HCTZ	Total
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks	Total of all reporting groups
Overall Participants	228	223	451
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.5 (7.57)	65.1 (6.96)	64.8 (7.27)
Sex: Female, Male (Count of Participants)
Female	127 55.7%	100 44.8%	227 50.3%
Male	101 44.3%	123 55.2%	224 49.7%

Outcome Measures

1. Primary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to Week 4
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Measure Participants	225	222
Least Squares Mean (Standard Error) [mm Hg]	-29.6 (1.0)	-22.3 (1.0)

2. Secondary Outcome

Title	Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to Week 4
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set, restricted to baseline msDBP >= 90 mmHg

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Measure Participants	130	133
Least Squares Mean (Standard Error) [mm Hg]	-11.1 (0.8)	-9.2 (0.8)

3. Secondary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic Blood Pressure (msDBP) (in Patients With msDBP ≥90 mmHg at Baseline) From Baseline to Week 8
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Full analysis set, restricted for msDBP to those with baseline msDBP at least 90 mm Hg)

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Measure Participants	225	222
msSBP	-33.2 (1.0)	-25.7 (1.0)
msDBP (N = 130 , 133)	-13.3 (0.8)	-10.1 (0.8)

4. Secondary Outcome

Title	Percentage of Responders at Week 4 and Week 8
Description	Responders defined as mean sitting Systolic Blood Pressure < 140 mmHg or reduction of ≥ 20 mmHg from baseline
Time Frame	At 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Measure Participants	225	222
Week 4	73.3 32.1%	55.9 25.1%
Week 8	83.1 36.4%	67.6 30.3%

5. Secondary Outcome

Title	Percentage of Subjects Achieving Blood Pressure Control at Weeks 4 and 8
Description	Blood pressure control defined as mean sitting Systolic Blood Pressure < 140 mm Hg and mean sitting Diastolic Blood Pressure < 90 mm Hg
Time Frame	At Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Aliskiren/HCTZ	HCTZ
Arm/Group Description	Aliskiren / Hydrochlorothiazide (HCTZ) 150/12.5 mg: 1 week, Aliskiren / HCTZ 300/25 mg (with or without amlodipine): 7 weeks	Hydrochlorothiazide (HCTZ) 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
Measure Participants	225	222
week 4	49.8 21.8%	33.3 14.9%
week 8	62.2 27.3%	39.2 17.6%

Adverse Events

Adverse Event Reporting Description	One patient was excluded from this analysis as he/she was inadvertently randomized into the study but did not receive study drug.
Arm/Group Title	Aliskiren / HCTZ		HCTZ
Arm/Group Description	Aliskiren HCTZ 150/12.5 mg: 1 week, Aliskiren HCTZ 300/25 mg (with or without amlodipine): 7 weeks		HCTZ 12.5 mg: 1 week, HCTZ 25 mg (with or without amlodipine): 7 weeks
All Cause Mortality
	Aliskiren / HCTZ		HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren / HCTZ		HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/227 (1.8%)		3/223 (1.3%)
Gastrointestinal disorders
Colitis	1/227 (0.4%)		0/223 (0%)
General disorders
Non-cardiac chest pain	0/227 (0%)		1/223 (0.4%)
Injury, poisoning and procedural complications
Subdural haematoma	0/227 (0%)		1/223 (0.4%)
Wrist fracture	0/227 (0%)		1/223 (0.4%)
Investigations
Renal function test abnormal	1/227 (0.4%)		0/223 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/227 (0.4%)		0/223 (0%)
Nervous system disorders
Cerebrovascular accident	1/227 (0.4%)		0/223 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren / HCTZ		HCTZ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/227 (7.5%)		26/223 (11.7%)
Nervous system disorders
Dizziness	13/227 (5.7%)		9/223 (4%)
Headache	4/227 (1.8%)		17/223 (7.6%)

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.