A Multi-Risk Factor Strategy vs a Guideline-Based Approach in Achieving Blood Pressure and Lipid Goals in Hypertensives at Extra Risk

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether an aggressive multi-risk factor management strategy (Caduet plus therapeutic lifestyle changes (TLC) regimen) will result in greater percentage of patients achieving blood pressure and low density lipoprotein cholesterol (LDL-C) goals compared with a Joint National Committee 7/ National Cholesterol Education Program Adult Treatment Panel III (JNC 7/NCEP ATP III) guideline-based approach (Norvasc plus TLC regimen) after 6 weeks of treatment in primary prevention subjects with hypertension and additional risk factors, including dyslipidemia.

Official Title
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A 6-Week, Prospective, Randomized, Double-Blind, Double-Dummy Phase IV Clinical Trial Designed to Evaluate the Efficacy of an Aggressive Multi-Risk Factor Management Strategy With Caduet (A3841045) Versus a Guideline-Based Approach in Achieving Blood Pressure and Lipid Goals in Hypertensive Subjects With Additional Risk Factors.

Conditions
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Dyslipidemia, Hypertension

Intervention / Treatment
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* Drug: Amlodipine besylate
* Drug: Amlodipine besylate/atorvastatin calcium single pill combination
* Drug: Amlodipine besylate
* Drug: Amlodipine besylate/atorvastatin calcium single pill combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with diagnosed hypertension receiving treatment with Norvasc 5 or 10 mg and who also have 3 additional cardiovascular risk factors, including dyslipidemia. Exclusion Criteria: Subjects who are taking the following prohibited medications within 14 days of screening: lipid-lowering therapy, calcium channel blocker other then Norvasc, >3 antihypertensive agents (including Norvasc) Subjects that have not been on a stable dose of Norvasc for at least 4 weeks Subjects with a history of coronary heart disease, stroke, or Pulmonary Vascular Disease (PVD)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Norvasc 5 mg<br>Blinded amlodipine 5 mg and amlodipine/atorvastatin single pill combination 5/20 mg placebo dosed once daily for 6 weeks. | Drug: Amlodipine besylate<br>* Amlodipine besylate 5 mg<br>|
| Experimental: Caduet 10/20mg<br>Blinded amlodipine/atorvastatin single pill combination 10/20 mg dosed once daily for 6 weeks and amlodipine besylate 10 mg placebo. | Drug: Amlodipine besylate/atorvastatin calcium single pill combination<br>* Amlodipine/atorvastatin single pill combination 10/20 mg<br>|
| Active Comparator: Norvasc 10 mg<br>Blinded amlodipine 19 mg and amlodipine/atorvastatin single pill combination 10/20 mg placebo dosed once daily for 6 weeks. | Drug: Amlodipine besylate<br>* Amlodipine besylate 10 mg<br>|
| Experimental: Caduet 5/20mg<br>Blinded amlodipine/atorvastatin single pill combination 5/20 mg and amlodipine besylate 5 mg placebo dosed once daily for 6 weeks . | Drug: Amlodipine besylate/atorvastatin calcium single pill combination<br>* Amlodipine/atorvastatin single pill combination 5/20 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Blood Pressure (BP) <140/90 Millimeters of Mercury (mmHg) and Low Density Lipoprotein Cholesterol (LDL-C) <100 Milligrams Per Deciliter(mg/dL) at Week 6 | Number of subjects reaching dual goal of systolic blood pressure <140 millimeters of mercury (mmHg) and diastolic blood pressue of <90 mmHg and low density lipoprotein-cholesterol(LDL-C) <100 milligrams per deciliter(mg/dL) | Week 6 | 
| Change From Baseline to Week 6 in Framingham Predicted Absolute 10-year Risk | Framingham prediction of absolute 10-year risk of Coronary Heart Disease (CHD) outcomes (myocardial infarction [MI] or CHD death) are calculations based on total point score (range less than negative 3 [best] to greater than or equal to 14 [worst] for men; less than or equal to negative 2 [best] and greater than or equal to 17 [worst] for women) of subject age, sex, current blood pressure treatment status, current smoking status, total cholesterol, high-density lipoprotein cholesterol, and systolic blood pressure calculated at Week 6. Mean at observation minus mean at baseline. | Week 6, baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Blood Pressure of <140/90 mmHg and LDL-C <100 mg/dL at Week 4 | Subjects achieving both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)-7 blood pressure goal of <140/90 mmHg and the National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP) III Update low density lipoprotein-cholesterol (LDL-C) goal <100 mg/dL at Week 4. | Week 4 | 
| Subjects With BP <140/90 mmHg and LDL-C <130 mg/dL at Week 4. | Subjects achieving both JNC-7 blood pressure goal of <140/90 mmHg and NCEP/ATP III LDL-C goal <130 mg/dL at Week 4. | Week 4 | 
| Subjects With BP <140/90 mmHg and LDL-C <130 mg/dL at Week 6. | Subjects achieving both JNC-7 blood pressure goal of <140/90 mmHg and NCEP/ATP III LDL-C goal <130 mg/dL at Week 6. | Week 6 | 
| Subjects With LDL-C < 100 mg/dL at Week 4 | Subjects Who achieve a goal of LDL-C < 100 mg/dL at Week 4. | Week 4 | 
| Subjects With LDL-C < 100 mg/dL at Week 6 | Subjects Who achieve a goal of LDL-C < 100 mg/dL at Week 6. | Week 6 | 
| Subjects With BP < 140/90 mmHg at Week 4 | Subjects achieving BP goal of <140/90 mmHg at week 4 | Week 4 | 
| Subjects With BP < 140/90 mmHg at Week 6 | Subjects achieving BP goal of <140/90 mmHg at week 6 | Week 6 | 
| Change From Baseline to Week 4 in Systolic Blood Pressure (SBP). | Mean at observation minus mean at baseline | Week 4, baseline | 
| Change From Baseline to Week 4 in Diastolic Blood Pressure (DBP) | Mean at observation minus mean at baseline | Week 4, baseline | 
| Change From Baseline to Week 4 in Pulse Rate | Mean at observation minus mean at baseline measured in beats per minute (bpm). | Week 4, baseline | 
| Change From Baseline to Week 6 in Systolic Blood Pressure (SBP) | Mean change at observation minus mean baseline. | Week 6, baseline | 
| Change From Baseline to Week 6 in Diastolic Blood Pressue (DBP) | Change from mean at observation minus mean at baseline | Week 6, baseline | 
| Change From Baseline to Week 6 in Pulse Rate | Mean at observation minus mean at baseline | Week 6, baseline | 
| Change From Baseline in LDL at Week 4. | Change: mean of observation minus mean at baseline. | Week 4, baseline | 
| Change From Baseline in High Density Lipoprotein (HDL) at Week 4. | Mean change at observation minus baseline. | Week 4, baseline | 
| Change in Total Cholesterol (TC) From Baseline to Week 4. | Mean change at observation minus baseline. | Week 4, baseline | 
| Change From Baseline in Triglycerides (TG) to Week 4. | Mean change at observation minus baseline | Week 4, baseline | 
| Change From Baseline in LDL at Week 6. | Mean change at observation minus baseline. | Week 6, baseline | 
| Change From Baseline in HDL at Week 6. | Mean change at observation minus baseline. | Week 6, baseline | 
| Change From Baseline in Total Cholesterol (TC) to Week 6. | Mean change at observation minus baseline. | Week 6, baseline | 
| Change From Baseline in Triglycerides (TG) at Week 6. | Mean change at observation minus mean baseline. | Week 6 , baseline | 
| Change From Baseline to Week 4 in Framingham Predicted Absolute 10-year Risk. | Framingham prediction of absolute 10-year risk of CHD outcomes (MI or CHD death) are calculations based on total point score (range less than negative 3 [best] to greater than or equal to 14 [worst] for men; less than or equal to negative 2 [best] and greater than or equal to 17 [worst] for women) of subject age, sex, current blood pressure treatment status, current smoking status, total cholesterol, high-density lipoprotein cholesterol and systolic blood pressure calculated at Week 4. Mean at observation minus mean at baseline. | Week 4, baseline |