Efficacy and Safety of Aliskiren/Amlodipine/Hydrochlorothiazide in Patients With Moderate-severe Hypertension

Phase 3

Completed

Conditions: Hypertension

Interventions: Drug: Aliskiren
Drug: Hydrochlorothiazide (HCTZ)
Drug: Amlodipine
Drug: Placebo

Registration Number: NCT00765674

Lead Sponsor: Novartis

Brief Summary: This study evaluated the efficacy (blood pressure lowering effect) and safety of aliskiren/amlodipine/hydrochlorothiazide in patients with moderate to severe hypertension.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1191

Inclusion Criteria

Male or female
18 years of age or older
msDBP and msSBP requirements:
- 3A:
  - Diagnosis of moderate to severe hypertension (msSBP ≥ 160 mmHg and < 200 mmHg, and/or msDBP ≥ 100 mmHg and < 120 mmHg) at Visits 4, 5 or 6 (Qualifying BP visit)
  - In addition, at the visit immediately prior to the above qualifying visit, patients were also to have msSBP ≥ 145 mmHg and < 200 mmHg and msDBP ≥ 95 mmHg and < 120 mmHg) at Visits 3, 5 or 5.
  - Patients had to meet the above two sets of requirements at subsequent adjacent visits, i.e. either Visits 3 and 4, Visits 4 and 5, or Visits 5 and 6.
- OR
- 3B:
  - msSBP ≥ 180 mmHg and < 200 mmHg with msDBP ≥ 95 mmHg and < 120 mmHg, or msDBP ≥ 110 mmHg and < 120 mmHg with msSBP ≥ 150 mmHg and < 200 mmHg after at least one week of treatment with placebo (Visit 3 and on).

Exclusion Criteria

Continued use of anti-hypertensive medicines or use of 4 or more hypertensive medicines at study start
Patients with an msSBP ≥ 200 mmHg or msDBP ≥ 120 mmHg at any time during the placebo run-in period were to be discontinued from the study.
Extremely elevated (defined) blood pressure at any point during the study
Pregnant or lactating women
Pre-menopausal women not taking accepted form of birth control
History or evidence of secondary form of hypertension
History of cardiovascular conditions

Other protocol-defined inclusion/exclusion criteria applied to the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aliskiren / hydrochlorothiazide	Hydrochlorothiazide (HCTZ)	Patients received an aliskiren 150 mg tablet plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo capsule and a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / hydrochlorothiazide	Placebo	Patients received an aliskiren 150 mg tablet plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo capsule and a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine	Placebo	Patients received an aliskiren 150 mg tablet plus an amlodipine 5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus amlodipine 10 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet and a placebo capsule. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Amlodipine / hydrochlorothiazide	Hydrochlorothiazide (HCTZ)	Patients received an amlodipine 5 mg capsule plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to amlodipine 10 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received 2 placebo tablets. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Amlodipine / hydrochlorothiazide	Placebo	Patients received an amlodipine 5 mg capsule plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to amlodipine 10 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received 2 placebo tablets. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine / hydrochlorothiazide	Hydrochlorothiazide (HCTZ)	Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine / hydrochlorothiazide	Placebo	Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine	Aliskiren	Patients received an aliskiren 150 mg tablet plus an amlodipine 5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus amlodipine 10 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet and a placebo capsule. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine	Amlodipine	Patients received an aliskiren 150 mg tablet plus an amlodipine 5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus amlodipine 10 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet and a placebo capsule. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / hydrochlorothiazide	Aliskiren	Patients received an aliskiren 150 mg tablet plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to aliskiren 300 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo capsule and a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Amlodipine / hydrochlorothiazide	Amlodipine	Patients received an amlodipine 5 mg capsule plus a hydrochlorothiazide 12.5 mg capsule for 4 weeks and then were force titrated up to amlodipine 10 mg plus hydrochlorothiazide 25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received 2 placebo tablets. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine / hydrochlorothiazide	Aliskiren	Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.
Aliskiren / amlodipine / hydrochlorothiazide	Amlodipine	Patients received an aliskiren 150 mg tablet, a HCTZ 12.5 mg capsule and a placebo capsule for the first 3 days of treatment. Amlodipine 5 mg was then added for the remainder of the first 4 weeks of treatment. At the end of 4 weeks, patients were force titrated up to aliskiren / amlodipine / hydrochlorothiazide 300/10/25 mg for the remaining 4 weeks of the study. During the 8 weeks, patients also received a placebo tablet. Patients took a total of 4 pills each day orally with water in the morning at approximately 8:00 am, except on the morning of a study visit when they took their study medications after all visit procedures and assessments had been completed.

Primary Outcome Measures

Name	Time	Method
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)	Baseline to end of study (Week 8)	Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0.5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.

Secondary Outcome Measures

Name	Time	Method
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)	Baseline to end of study (Week 8)	Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. If there was \< 0.5 mmHg difference in BP between the 2 arms, the non-dominant arm was used. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated. A negative change indicates lowered BP.
Percentage of Patients Achieving Blood Pressure Control at the End of the Study (Week 8)	End of study (Week 8)	Blood pressure control was defined as a msSBP/msDBP \< 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured at trough (24±3 hours post-dose). The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position with the back supported and both feet placed on the floor for 5 minutes, systolic and diastolic BP were measured 3 times with an automated BP monitor and appropriate size cuff. Means of the 3 measurements were calculated.
Change in Mean 24-hour Ambulatory Systolic and Diastolic Blood Pressure From Baseline to End of Study (Week 8)	Baseline to end of study (Week 8)	Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed in a subset of patients twice during the study, once at baseline and again at Week 8. The ABPM device was placed on the non-dominant arm between 7:00 and 10:00 am and verification readings obtained. If they were successful, the investigator initiated the 24 hour reading and instructed the patient regarding ABPM procedures. On the next day, the ABPM device was removed if it had been worn for a minimum of 24 hours. The ABPM data were downloaded and evaluated on site.