Safety and Efficacy of Aliskiren 300 mg, 150 mg and 75 mg in Patients With Essential Hypertension Compared to Ramipril 5 mg

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00529451
• Collaborator: (none)
• Enrollment: 1,613
• Locations: 3
• Arms: 4
• Duration (Months): 10
• Patients Per Site: 537.7
• Patients Per Site Per Month: 53.8

Study Details

Study Description

Brief Summary

This study is designed to investigate the efficacy, safety and tolerability of aliskiren 300 mg, 150 mg and 75 mg when compared to ramipril 5 mg in patients with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren; Drug: Ramipril	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1613 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: An Eight Week, Double-blind, Randomized, Multicenter, Parallel Group, Active-controlled Study Comparing the Safety and Efficacy of Aliskiren 300 mg, 150 mg and 75 mg to Ramipril 5 mg in Patients With Essential Hypertension
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aliskiren 300 mg Aliskiren 300 mg once daily	Drug: Aliskiren; Aliskiren
Experimental: Aliskiren 150 mg Aliskiren 150 mg once daily	Drug: Aliskiren; Aliskiren
Experimental: Aliskiren 75 mg Aliskiren 75 mg once daily	Drug: Aliskiren; Aliskiren
Active Comparator: Ramipril 5 mg Ramipril 5 mg once daily	Drug: Ramipril; comparator

Outcome Measures

Primary Outcome Measures

1. Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) [Baseline and Week 8]

   To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint

2. Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) [Baseline and Week 8]

   To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint

3. Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP) [Baseline and Week 8]

   To evaluate the non-inferiority of aliskiren 75 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint

Secondary Outcome Measures

1. Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint [Baseline and Week 8]

   To evaluate the change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic blood Pressure (msDBP) from baseline to 8 week endpoint on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg in patients with essential hypertension.

2. Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg [Week 8]

   To evaluate the percentage of patients controlled to a target blood pressure of < 140/90 mmHg on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg.

3. Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP [Week 8]

   To evaluate the percentage of responders on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg, defined as msDBP < 90 mmHg or ≥ 10mmHg decrease from baseline in msDBP.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have msDBP ≥ 90 mmHg and < 110 mmHg at the visit immediately prior to Visit 3

• Patients must have msDBP >OR= 95 mmHg and < 110 mmHg at Visit 3

• Patients must have an absolute difference of < or =10 mmHg in their mean sitting diastolic blood pressure (msDBP) from Visit 2 to Visit 3

Exclusion Criteria:

• Severe hypertension (grade 3 WHO classification; msDBP >or= 110 mmHg and/or msSBP >or = 180 mmHg).

• History or evidence of a secondary form of hypertension.

• History of transient ischemic cerebral attack within 12 months of visit 1.

• Current angina pectoris requiring pharmacological therapy (other than those patients on a stable dose of oral or topical nitrates)

• Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) > 8% at Visit

• Known or suspected contraindications to the study medications, including history of allergy to ramipril or other ACE Inhibitors.

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Sites	China		China
2	Novartis Investigative Sites	India		India
3	Novartis Investigative Sites	Thailand		Thailand

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00529451
• Other Study ID Numbers: CSPP100A2339
• First Posted: Sep 14, 2007
• Last Update Posted: Mar 25, 2011
• Last Verified: Feb 1, 2011

• Keywords provided by , ,: Hypertension, Aliskiren, Ramipril
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Ramipril

Study Results

Participant Flow

Arm/Group Title	Aliskiren 300 mg	Aliskiren 150 mg	Aliskiren 75 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily	Aliskiren 150 mg once daily	Aliskiren 75 mg once daily	Ramipril 5 mg once daily
Period Title: Overall Study
STARTED	331	323	332	330
COMPLETED	294	275	292	299
NOT COMPLETED	37	48	40	31

Baseline Characteristics

Arm/Group Title	Aliskiren 300 mg	Aliskiren 150 mg	Aliskiren 75 mg	Ramipril 5 mg	Total
Arm/Group Description	Aliskiren 300 mg once daily	Aliskiren 150 mg once daily	Aliskiren 75 mg once daily	Ramipril 5 mg once daily	Total of all reporting groups
Overall Participants	331	323	332	330	1316
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (9.45)	53.3 (10.53)	52.7 (10.22)	52.9 (9.60)	53.2 (9.95)
Age, Customized (Number) [Number]
< 65 years	288 87%	273 84.5%	285 85.8%	296 89.7%	1142 86.8%
≥ 65 years	43 13%	50 15.5%	47 14.2%	34 10.3%	174 13.2%
Sex: Female, Male (Count of Participants)
Female	150 45.3%	140 43.3%	144 43.4%	151 45.8%	585 44.5%
Male	181 54.7%	183 56.7%	188 56.6%	179 54.2%	731 55.5%

Outcome Measures

1. Secondary Outcome

Title	Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint
Description	To evaluate the change in Mean Sitting Systolic Blood Pressure (msSBP) and Mean Sitting Diastolic blood Pressure (msDBP) from baseline to 8 week endpoint on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg in patients with essential hypertension.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 300 mg	Aliskiren 150 mg	Aliskiren 75 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily	Aliskiren 150 mg once daily	Aliskiren 75 mg once daily	Ramipril 5 mg once daily
Measure Participants	327	318	324	323
msSBP	-14.39 (0.66)	-12.16 (0.67)	-12.24 (0.66)	-11.46 (0.66)
msDBP	-11.63 (0.44)	-10.04 (0.44)	-10.66 (0.44)	-9.19 (0.44)

2. Secondary Outcome

Title	Evaluation of the Percentage of Patients Controlled to a Target Blood Pressure of < 140/90 mmHg on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg
Description	To evaluate the percentage of patients controlled to a target blood pressure of < 140/90 mmHg on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 300 mg	Aliskiren 150 mg	Aliskiren 75 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily	Aliskiren 150 mg once daily	Aliskiren 75 mg once daily	Ramipril 5 mg once daily
Measure Participants	327	318	324	323
Number [Percentage of participants]	52.29 15.8%	48.11 14.9%	45.68 13.8%	43.65 13.2%

3. Secondary Outcome

Title	Evaluation of the Percentage of Responders on Aliskiren 300 mg, 150 mg and 75 mg vs. Ramipril 5 mg, Define as msDBP < 90 mmHg or ≥ 10mmHg Decrease From Baseline in msDBP
Description	To evaluate the percentage of responders on aliskiren 300 mg, 150 mg and 75 mg vs. ramipril 5 mg, defined as msDBP < 90 mmHg or ≥ 10mmHg decrease from baseline in msDBP.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 300 mg	Aliskiren 150 mg	Aliskiren 75 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily	Aliskiren 150 mg once daily	Aliskiren 75 mg once daily	Ramipril 5 mg once daily
Measure Participants	327	318	324	323
Number [Percentage of participants]	67.89 20.5%	59.75 18.5%	59.57 17.9%	53.87 16.3%

4. Primary Outcome

Title	Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
Description	To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 300 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily	Ramipril 5 mg once daily
Measure Participants	327	323
Least Squares Mean (Standard Error) [mm Hg]	-11.63 (0.44)	-9.19 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aliskiren 300 mg, Aliskiren 150 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 2.25 mm Hg
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.44
	Confidence Interval	(2-Sided) 95%; -3.63 to -1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
Description	To evaluate the non-inferiority of aliskiren 300 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 150 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 150 mg once daily	Ramipril 5 mg once daily
Measure Participants	318	323
Least Squares Mean (Standard Error) [mm Hg]	-10.04 (0.44)	-9.19 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aliskiren 300 mg, Aliskiren 150 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 2.25 mm Hg
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 95%; -2.06 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)
Description	To evaluate the non-inferiority of aliskiren 75 mg to ramipril 5 mg in the change in Mean Sitting Diastolic Blood Pressure (msDBP) from baseline to 8 week endpoint
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat. Analyzed patients received at least one dose of study drug and had a post baseline measurement.

Arm/Group Title	Aliskiren 75 mg	Ramipril 5 mg
Arm/Group Description	Aliskiren 75 mg once daily	Ramipril 5 mg once daily
Measure Participants	324	323
Least Squares Mean (Standard Error) [mm Hg]	-10.66 (0.44)	-9.19 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aliskiren 300 mg, Aliskiren 150 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority margin of 2.25 mm Hg
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -2.67 to -0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	8 weeks
Adverse Event Reporting Description	One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Arm/Group Title	Aliskiren 300 mg		Aliskiren 150 mg		Aliskiren 75 mg		Ramipril 5 mg
Arm/Group Description	Aliskiren 300 mg once daily		Aliskiren 150 mg once daily		Aliskiren 75 mg once daily		Ramipril 5 mg once daily
All Cause Mortality
	Aliskiren 300 mg		Aliskiren 150 mg		Aliskiren 75 mg		Ramipril 5 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
	Aliskiren 300 mg		Aliskiren 150 mg		Aliskiren 75 mg		Ramipril 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/331 (0.3%)		2/323 (0.6%)		3/332 (0.9%)		1/329 (0.3%)
General disorders
Chest pain	0/331 (0%)		0/323 (0%)		1/332 (0.3%)		0/329 (0%)
Injury, poisoning and procedural complications
Head injury	0/331 (0%)		1/323 (0.3%)		0/332 (0%)		0/329 (0%)
Medical device complication	0/331 (0%)		0/323 (0%)		1/332 (0.3%)		0/329 (0%)
Nervous system disorders
Cerebral haemorrhage	0/331 (0%)		0/323 (0%)		1/332 (0.3%)		0/329 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	0/331 (0%)		1/323 (0.3%)		0/332 (0%)		0/329 (0%)
Vascular disorders
Hypertension	0/331 (0%)		0/323 (0%)		0/332 (0%)		1/329 (0.3%)
Varicose vein	1/331 (0.3%)		0/323 (0%)		0/332 (0%)		0/329 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren 300 mg		Aliskiren 150 mg		Aliskiren 75 mg		Ramipril 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/331 (1.2%)		3/323 (0.9%)		2/332 (0.6%)		17/329 (5.2%)
Respiratory, thoracic and mediastinal disorders
Cough	4/331 (1.2%)		3/323 (0.9%)		2/332 (0.6%)		17/329 (5.2%)

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.