Trial Outcomes & Findings for Safety and Efficacy of Aliskiren 300 mg, 150 mg and 75 mg in Patients With Essential Hypertension Compared to Ramipril 5 mg (NCT NCT00529451)

NCT ID: NCT00529451

Last Updated: 2011-03-25

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1613 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2011-03-25

Participant Flow

Participant milestones

Measure	Aliskiren 300 mg Aliskiren 300 mg once daily	Aliskiren 150 mg Aliskiren 150 mg once daily	Aliskiren 75 mg Aliskiren 75 mg once daily	Ramipril 5 mg Ramipril 5 mg once daily
Overall Study STARTED	331	323	332	330
Overall Study COMPLETED	294	275	292	299
Overall Study NOT COMPLETED	37	48	40	31

Reasons for withdrawal

Measure	Aliskiren 300 mg Aliskiren 300 mg once daily	Aliskiren 150 mg Aliskiren 150 mg once daily	Aliskiren 75 mg Aliskiren 75 mg once daily	Ramipril 5 mg Ramipril 5 mg once daily
Overall Study Subject withdrew consent	16	21	13	12
Overall Study Adverse Event	9	16	14	8
Overall Study Unsatisfactory therapeutic response	6	2	5	4
Overall Study Lost to Follow-up	4	7	4	4
Overall Study Protocol deviation	1	1	4	1
Overall Study Administrative problems	1	1	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Aliskiren 300 mg n=331 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg n=332 Participants Aliskiren 75 mg once daily	Ramipril 5 mg n=330 Participants Ramipril 5 mg once daily	Total n=1316 Participants Total of all reporting groups
Age Continuous	53.8 years STANDARD_DEVIATION 9.45 • n=93 Participants	53.3 years STANDARD_DEVIATION 10.53 • n=4 Participants	52.7 years STANDARD_DEVIATION 10.22 • n=27 Participants	52.9 years STANDARD_DEVIATION 9.60 • n=483 Participants	53.2 years STANDARD_DEVIATION 9.95 • n=36 Participants
Age, Customized < 65 years	288 Participants n=93 Participants	273 Participants n=4 Participants	285 Participants n=27 Participants	296 Participants n=483 Participants	1142 Participants n=36 Participants
Age, Customized ≥ 65 years	43 Participants n=93 Participants	50 Participants n=4 Participants	47 Participants n=27 Participants	34 Participants n=483 Participants	174 Participants n=36 Participants
Sex: Female, Male Female	150 Participants n=93 Participants	140 Participants n=4 Participants	144 Participants n=27 Participants	151 Participants n=483 Participants	585 Participants n=36 Participants
Sex: Female, Male Male	181 Participants n=93 Participants	183 Participants n=4 Participants	188 Participants n=27 Participants	179 Participants n=483 Participants	731 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

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

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

Outcome measures

Measure	Aliskiren 300 mg n=327 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg Aliskiren 75 mg once daily	Ramipril 5 mg Ramipril 5 mg once daily
Non-inferiority of Aliskiren 300 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)	-11.63 mm Hg Standard Error 0.44	-9.19 mm Hg Standard Error 0.44	—	—

PRIMARY outcome

Timeframe: Baseline and Week 8

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

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

Outcome measures

Measure	Aliskiren 300 mg n=318 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg Aliskiren 75 mg once daily	Ramipril 5 mg Ramipril 5 mg once daily
Non-inferiority of Aliskiren 150 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)	-10.04 mm Hg Standard Error 0.44	-9.19 mm Hg Standard Error 0.44	—	—

PRIMARY outcome

Timeframe: Baseline and Week 8

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

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

Outcome measures

Measure	Aliskiren 300 mg n=324 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg Aliskiren 75 mg once daily	Ramipril 5 mg Ramipril 5 mg once daily
Non-inferiority of Aliskiren 75 mg to Ramipril 5 mg in Change in Mean Sitting Diastolic Blood Pressure (msDBP)	-10.66 mm Hg Standard Error 0.44	-9.19 mm Hg Standard Error 0.44	—	—

SECONDARY outcome

Timeframe: Baseline and Week 8

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

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.

Outcome measures

Measure	Aliskiren 300 mg n=327 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=318 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg n=324 Participants Aliskiren 75 mg once daily	Ramipril 5 mg n=323 Participants Ramipril 5 mg once daily
Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint msDBP	-11.63 mm Hg Standard Error 0.44	-10.04 mm Hg Standard Error 0.44	-10.66 mm Hg Standard Error 0.44	-9.19 mm Hg Standard Error 0.44
Change in Mean Sitting Systolic Blood Pressure (msSBP)and Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to 8 Week Endpoint msSBP	-14.39 mm Hg Standard Error 0.66	-12.16 mm Hg Standard Error 0.67	-12.24 mm Hg Standard Error 0.66	-11.46 mm Hg Standard Error 0.66

SECONDARY outcome

Timeframe: Week 8

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

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.

Outcome measures

Measure	Aliskiren 300 mg n=327 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=318 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg n=324 Participants Aliskiren 75 mg once daily	Ramipril 5 mg n=323 Participants Ramipril 5 mg once daily
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	52.29 Percentage of participants	48.11 Percentage of participants	45.68 Percentage of participants	43.65 Percentage of participants

SECONDARY outcome

Timeframe: Week 8

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

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.

Outcome measures

Measure	Aliskiren 300 mg n=327 Participants Aliskiren 300 mg once daily	Aliskiren 150 mg n=318 Participants Aliskiren 150 mg once daily	Aliskiren 75 mg n=324 Participants Aliskiren 75 mg once daily	Ramipril 5 mg n=323 Participants Ramipril 5 mg once daily
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	67.89 Percentage of participants	59.75 Percentage of participants	59.57 Percentage of participants	53.87 Percentage of participants

Adverse Events

Aliskiren 300 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Aliskiren 150 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Aliskiren 75 mg

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Ramipril 5 mg

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aliskiren 300 mg n=331 participants at risk Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 participants at risk Aliskiren 150 mg once daily	Aliskiren 75 mg n=332 participants at risk Aliskiren 75 mg once daily	Ramipril 5 mg n=329 participants at risk Ramipril 5 mg once daily
General disorders Chest pain	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.30% 1/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Injury, poisoning and procedural complications Head injury	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.31% 1/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Injury, poisoning and procedural complications Medical device complication	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.30% 1/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Nervous system disorders Cerebral haemorrhage	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.30% 1/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.31% 1/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Vascular disorders Hypertension	0.00% 0/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.30% 1/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.
Vascular disorders Varicose vein	0.30% 1/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.00% 0/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.

Other adverse events

Measure	Aliskiren 300 mg n=331 participants at risk Aliskiren 300 mg once daily	Aliskiren 150 mg n=323 participants at risk Aliskiren 150 mg once daily	Aliskiren 75 mg n=332 participants at risk Aliskiren 75 mg once daily	Ramipril 5 mg n=329 participants at risk Ramipril 5 mg once daily
Respiratory, thoracic and mediastinal disorders Cough	1.2% 4/331 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.93% 3/323 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	0.60% 2/332 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.	5.2% 17/329 • 8 weeks One randomized patient in the Ramipril group never received blinded study medication. The subject is therefore not included in the "at risk" population.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER