Efficacy and Tolerability of an Aliskiren-based Treatment Algorithm in Patients With Mild to Moderate Hypertension

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00765947
• Collaborator: (none)
• Enrollment: 256
• Locations: 4
• Arm: 1
• Actual Duration (Months): 11
• Patients Per Site: 64
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

This study will assess the efficacy of an aliskiren based treatment regimen in reaching blood pressure (BP) target in patients with mild to moderate hypertension. (defined as mean sitting Systolic Blood Pressure [msSBP] ≥ 140 mmHg and < 180 mmHg and/or mean sitting Diastolic Blood Pressure [msDBP] ≥ 90 and <110 mmHg).

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension ( Mild to Moderate)	Drug: Aliskiren; Drug: Hydrochlorothiazide; Drug: Amlodipine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Twenty-four Week, Open-label, Non-comparative, Multi-center Study to Assess the Efficacy and Tolerability of an Aliskiren-based Treatment Algorithm in Patients With Mild to Moderate Hypertension.
• Actual Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren-based regimen All pts starting on aliskiren 150 mg (uptitrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (uptitrated to 25 mg) and amlodipine 5 mg (uptitrated to 10 mg), as necessary to achieve the Blood Pressure goal.	Drug: Aliskiren; Aliskiren 150 or 300 mg; Drug: Hydrochlorothiazide; Hydrochlorothiazide 12.5 or 25 mg; Drug: Amlodipine; Amlodipine 5 or 10 mg

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants (Defined as Estimated Cumulative Control Rate) Reaching Blood Pressure Target in a Stepped Care, Aliskiren-based Regimen [24 weeks]

   For non diabetic patients the Blood Pressure target is defined as mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg and for diabetic patients the Blood Pressure target is mean sitting Systolic Blood Pressure [msSBP] < 130 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 80 mmHg.

Secondary Outcome Measures

1. Percentage of Patients (Defined as Estimated Cumulative Control Rate) Reaching Blood Pressure Target in a Stepped-care, Aliskiren-based Regimen by Patient Subgroups of Mild and Moderate Hypertensive Patients, and Non-diabetic and Diabetic Patients. [24 weeks]

   For non diabetic patients the Blood Pressure target is defined as mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg and for diabetic patients the Blood Pressure target is mean sitting Systolic Blood Pressure [msSBP] < 130 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 80 mmHg.

2. Changes From Baseline to Week 24 in Mean Sitting Systolic Blood Pressure [msSBP] and Mean Sitting Diastolic Blood Pressure [msDBP] [Baseline and Week 24]

3. Percent of Responders for Mean Sitting Systolic Blood Pressure [msSBP] and for Mean Sitting Diastolic Blood Pressure [msDBP] [24 weeks]

   Response for mean sitting Systolic Blood Pressure [msSBP] is defined as a reduction of ≥ 20 mmHg from baseline or mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg (non diabetics) or < 130 mmHg (diabetics). Response for mean sitting Diastolic Blood Pressure [msDBP] is defined as a reduction of ≥10 mmHg from baseline or mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg (non diabetic) or < 80 mmHg (diabetics).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Outpatients ≥ 18 years of age

• Patients with a diagnosis of mild to moderate hypertension at Visit 1

• All patients must have a msSBP ≥ 140 mmHg and < 180 mmHg and/or msDBP ≥ 90 mmHg and < 110 mmHg mmHg at Visit 3

Exclusion Criteria:

• Severe hypertension defined as msSBP ≥ 180 mmHg and/or msDBP ≥ 110 mmHg

• Secondary form of hypertension

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

• Current angina pectoris requiring pharmacological therapy (other than stable doses of oral or topical nitrates)

• Second or third degree heart block without a pacemaker

• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, atrial fibrillation or atrial flutter, during the 12 months prior to Visit 1

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Paris		France
2	Investigative Site	Budapest		Hungary
3	Investigative Site	Bucharest		Romania
4	Investigative Site	Bratislava		Slovakia

Sponsors and Collaborators

• Novartis

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00765947
• Other Study ID Numbers: CSPP100A2360
• First Posted: Oct 3, 2008
• Last Update Posted: Aug 6, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Novartis: Essential Hypertension ( mild to moderate)
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Amlodipine; Hydrochlorothiazide

Study Results

Participant Flow

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Period Title: Overall Study
STARTED	256
COMPLETED	232
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Overall Participants	256
Age, Customized (participants) [Number]
< 65 yrs	203 79.3%
≥ 65 yrs	53 20.7%
Sex: Female, Male (Count of Participants)
Female	113 44.1%
Male	143 55.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants (Defined as Estimated Cumulative Control Rate) Reaching Blood Pressure Target in a Stepped Care, Aliskiren-based Regimen
Description	For non diabetic patients the Blood Pressure target is defined as mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg and for diabetic patients the Blood Pressure target is mean sitting Systolic Blood Pressure [msSBP] < 130 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 80 mmHg.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Measure Participants	256
Number [Percentage of participants]	86.12 33.6%

2. Secondary Outcome

Title	Percentage of Patients (Defined as Estimated Cumulative Control Rate) Reaching Blood Pressure Target in a Stepped-care, Aliskiren-based Regimen by Patient Subgroups of Mild and Moderate Hypertensive Patients, and Non-diabetic and Diabetic Patients.
Description	For non diabetic patients the Blood Pressure target is defined as mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg and for diabetic patients the Blood Pressure target is mean sitting Systolic Blood Pressure [msSBP] < 130 mmHg and mean sitting Diastolic Blood Pressure [msDBP] < 80 mmHg.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Measure Participants	256
Mild Hypertensive	91.48 35.7%
Moderate Hypertensive	79.24 31%
Non-diabetic	92.74 36.2%
Diabetic	72.58 28.4%

3. Secondary Outcome

Title	Changes From Baseline to Week 24 in Mean Sitting Systolic Blood Pressure [msSBP] and Mean Sitting Diastolic Blood Pressure [msDBP]
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Measure Participants	251
msSBP	-25.33 (13.942)
msDBP	-12.40 (9.371)

4. Secondary Outcome

Title	Percent of Responders for Mean Sitting Systolic Blood Pressure [msSBP] and for Mean Sitting Diastolic Blood Pressure [msDBP]
Description	Response for mean sitting Systolic Blood Pressure [msSBP] is defined as a reduction of ≥ 20 mmHg from baseline or mean sitting Systolic Blood Pressure [msSBP] < 140 mmHg (non diabetics) or < 130 mmHg (diabetics). Response for mean sitting Diastolic Blood Pressure [msDBP] is defined as a reduction of ≥10 mmHg from baseline or mean sitting Diastolic Blood Pressure [msDBP] < 90 mmHg (non diabetic) or < 80 mmHg (diabetics).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren-based Regimen
Arm/Group Description	Patients initiated treatment with aliskiren 150 mg (up-titrated to aliskiren 300 mg), followed by the addition of HCTZ 12.5 mg (up-titrated to 25 mg) and amlodipine 5 mg (up-titrated to 10 mg), as necessary to achieve the Blood Pressure goal.
Measure Participants	256
msSBP	96.80 37.8%
msDBP	97.78 38.2%

Adverse Events

Arm/Group Title	Aliskiren		Aliskiren + HCTZ		Aliskiren + HCTZ + Amlodipine
Arm/Group Description	Aliskiren treatment step		Aliskiren and HCTZ treatment step		Aliskiren + HCTZ + Amlodipine treatment step
All Cause Mortality
	Aliskiren		Aliskiren + HCTZ		Aliskiren + HCTZ + Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Aliskiren + HCTZ		Aliskiren + HCTZ + Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/256 (1.2%)		0/197 (0%)		0/119 (0%)
Cardiac disorders
Myocardial infarction	1/256 (0.4%)		0/197 (0%)		0/119 (0%)
General disorders
Non-cardiac chest pain	1/256 (0.4%)		0/197 (0%)		0/119 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm	1/256 (0.4%)		0/197 (0%)		0/119 (0%)
Vascular disorders
Hypertension	1/256 (0.4%)		0/197 (0%)		0/119 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren		Aliskiren + HCTZ		Aliskiren + HCTZ + Amlodipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/256 (0%)		0/197 (0%)		0/119 (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.