Trial Outcomes & Findings for Blood Pressure Lowering of Aliskiren Hydrochlorothiazide (HCTZ) Versus Amlodipine in Stage 2 Hypertension in African Americans (NCT NCT00739596)

NCT ID: NCT00739596

Last Updated: 2016-10-27

Results Overview

To assess the change from baseline in MSSBP after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 332 participants
• Primary outcome timeframe: Baseline and 8 weeks
• Results posted on: 2016-10-27

Participant Flow

Participant milestones

Measure	Aliskiren Hydrochlorothiazide (HCTZ) Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Overall Study STARTED	166	166
Overall Study COMPLETED	141	149
Overall Study NOT COMPLETED	25	17

Reasons for withdrawal

Measure	Aliskiren Hydrochlorothiazide (HCTZ) Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Overall Study Adverse Event	12	6
Overall Study Unsatisfactory Therapeutic Effect	4	0
Overall Study Patient Withdrew Consent	8	8
Overall Study Lost to Follow-up	0	2
Overall Study Protocol Deviation	1	1

Baseline Characteristics

Blood Pressure Lowering of Aliskiren Hydrochlorothiazide (HCTZ) Versus Amlodipine in Stage 2 Hypertension in African Americans

Baseline characteristics by cohort

Measure	Aliskiren HCTZ n=166 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=166 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks	Total n=332 Participants Total of all reporting groups
Age, Customized < 65 years	141 participants n=5 Participants	143 participants n=7 Participants	284 participants n=5 Participants
Age, Customized ≥ 65 years	25 participants n=5 Participants	23 participants n=7 Participants	48 participants n=5 Participants
Age, Continuous	52.0 years STANDARD_DEVIATION 11.27 • n=5 Participants	53.1 years STANDARD_DEVIATION 11.56 • n=7 Participants	52.6 years STANDARD_DEVIATION 11.41 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	91 Participants n=7 Participants	176 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	75 Participants n=7 Participants	156 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 8 weeks

Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.

To assess the change from baseline in MSSBP after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.

Outcome measures

Measure	Aliskiren HCTZ n=162 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=162 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment Baseline	168.2 mm Hg Standard Deviation 8.49	168.1 mm Hg Standard Deviation 7.99
Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment Week 8	138.8 mm Hg Standard Deviation 18.21	139.1 mm Hg Standard Deviation 14.45
Change in Mean Sitting Systolic Blood Pressure (MSSBP) After 8 Weeks of Treatment Change from baseline to Week 8	-29.4 mm Hg Standard Deviation 17.95	-29.0 mm Hg Standard Deviation 13.17

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.

To assess the change from baseline in mean sitting diastolic blood pressure (MSDBP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.

Outcome measures

Measure	Aliskiren HCTZ n=162 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=162 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment Baseline	96.0 mm Hg Standard Deviation 9.76	95.0 mm Hg Standard Deviation 8.86
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment Week 8	86.0 mm Hg Standard Deviation 12.02	84.0 mm Hg Standard Deviation 9.72
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) After 8 Weeks of Treatment Change from Baseline to Week 8	-10.0 mm Hg Standard Deviation 11.08	-11.0 mm Hg Standard Deviation 9.81

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable. Last observation carried forward (LOCF) method was used for replacing missing values with post-baseline assessments.

To compare the change from baseline in mean sitting pulse pressure (MSPP) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.

Outcome measures

Measure	Aliskiren HCTZ n=162 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=162 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment Baseline	72.2 mm Hg Standard Deviation 12.10	73.1 mm Hg Standard Deviation 11.59
Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment Week 8	52.7 mm Hg Standard Deviation 14.91	55.1 mm Hg Standard Deviation 12.13
Change in Mean Sitting Pulse Pressure (MSPP) After 8 Weeks of Treatment Change from Baseline to Week 8	-19.4 mm Hg Standard Deviation 13.73	-18.0 mm Hg Standard Deviation 11.20

SECONDARY outcome

Timeframe: 8 weeks

Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable.

To compare the percentage of responders after 8 weeks of treatment with an aliskiren HCTZ based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension: [ Responders were defined as patients with MSSBP < 140 mm Hg or a decrease from baseline ≥ 20 mm Hg at 1st response. A response was counted when a patient first achieved MSSBP < 140 mm Hg or a decrease from baseline ≥ 20 mm Hg.]

Outcome measures

Measure	Aliskiren HCTZ n=162 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=162 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Percentage of Responders After 8 Weeks of Treatment.	84.6 Cumulative percentage of responders Interval -13.92 to 1.58	90.7 Cumulative percentage of responders Interval 13.92 to 1.58

SECONDARY outcome

Timeframe: 8 weeks

Population: The intent-to-treat (ITT) population consisted of all randomized patients who received at least one dose of study medication and had at least one valid post-baseline assessment of the primary efficacy variable.

To compare the percentage of patients achieving BP control (<140/90 mm Hg) after 8 weeks of treatment with an aliskiren HCTZ-based treatment regimen (aliskiren HCTZ 150/12.5 mg, 300/25 mg) versus an amlodipine-based treatment regimen (amlodipine 5 mg, 10 mg) in African American patients with stage 2 hypertension.

Outcome measures

Measure	Aliskiren HCTZ n=162 Participants Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks	Amlodipine n=162 Participants Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks
Percentage of Participants Achieving BP Control After 8 Weeks of Treatment	63.6 Cumulative percentage of participants Interval -9.9 to 12.37	62.3 Cumulative percentage of participants Interval -9.9 to 12.37

Adverse Events

Aliskiren HCTZ

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Amlodipine

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aliskiren HCTZ n=166 participants at risk Aliskiren HCTZ (150/12.5 mg) for 1 week followed by forced titration to Aliskiren HCTZ (300/25 mg) for remaining 7 weeks.	Amlodipine n=166 participants at risk Amlodipine 5 mg for 1 week followed by forced titration to Amlodipine 10 mg for remaining 7 weeks.
Cardiac disorders Acute myocardial infarction	0.60% 1/166 • 8 Weeks	0.60% 1/166 • 8 Weeks
Cardiac disorders Myocardial infarction	0.00% 0/166 • 8 Weeks	0.60% 1/166 • 8 Weeks
Infections and infestations Appendicitis	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks
Infections and infestations Cellulitis	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks
Infections and infestations Encephalitis herpes	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks
Metabolism and nutrition disorders Hypokalaemia	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.60% 1/166 • 8 Weeks	0.60% 1/166 • 8 Weeks
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks
Nervous system disorders Cerebral haemorrhage	0.60% 1/166 • 8 Weeks	0.00% 0/166 • 8 Weeks

Other adverse events

Adverse event data not reported

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