HYPERTENSION AND ADDITIONAL CARDIOVASCULAR RISK FACTORS. MedDRA version: 8.1 Level: LLT Classification code 10020772 Term: Hypertension
Conditions
Interventions
Trade Name: Caduet®
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Amlodipine besylate & Atorvastatin calcium
Other descriptive name: LI-900003-01
Concentration unit: mg/g milligram(s)/g
Sponsors
Pfizer Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial at screening and baseline: 1. Male or female. 2. Age 35-79 years. 3. Hypertension: Untreated SBP >160 mmHg and/or DBP >100 mmHg or treated SBP >140 mmHg and/or DBP >90 mmHg (or SBP >130 mmHg and/or DBP >80 mmHg in the presence of diabetes). 4. Total cholesterol = 6.5 mmol/L (250 mg/dl). 5. No history of coronary heart disease (CHD). 6. Three or more cardiovascular risk factors from the following list: Smoking - Type 2 diabetes - Left Ventricular Hypertrophy (LVH) by echocardiography or electrocardiography - Peripheral vascular disease - ECG abnormalities such as left ventricular strain pattern, Left Bundle Branch Block, ST-T changes compatible with myocardial ischemic heart disease. (ECG evidence of MI would exclude the subject) - Family history of early CHD before age 55 in first degree relative - History of stroke/ transient ischemic attack (TIA) more than 3 months before screening - Age over 55 (men) or 65 (women) - Plasma TC/HDL ratio = 6 or HDL below 1mmol/l (below 40mg/dl) 7. Subject who has signed the informed consent form. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following will not be included in the trial: 1. Subjects currently receiving statin therapy or stopped statin treatment within 6 months prior to enrollment. 2. Subjects with untreated SBP = 160 mmHg and DBP = 100 mmHg or treated SBP = 140 mmHg and DBP = 90 mmHg (or SBP = 130 mmHg and DBP = 80 mmHg in the presence of diabetes). 3. Pregnant or lactating women. Women of childbearing potential who are not using an acceptable method of contraception. 4. Subjects with a history of myocardial infarction and subjects with a history of coronary artery bypass or intra-coronary interventions. 5. Subjects with history of atherosclerotic brain infarction, stroke, or transient ischemic attack (TIA) within 3 months. 6. Subjects with chronic, sustained cardiac arrhythmias (including second or third degree atrioventricular (AV) block, sick sinus syndrome, atrial flutter or any arrhythmias requiring medications), or an accessory bypass track (e.g., Wolff Parkinson White or Lown Ganong Levine syndromes). However, Subjects with chronic, stable atrial fibrillation may be included. 7. Subjects with congestive heart failure of NYHA Class II, III or IV. 8. Subjects with secondary dyslipidemia of any etiology, such as nephrotic syndrome or Cushing’s syndrome. Subjects with hypothyroidism may be enrolled if they are on stable doses of thyroid replacement therapy and exhibit normal thyroid stimulating hormone (TSH) levels at baseline. 9. Subjects with secondary hypertension of any cause, including, but not limited to renal artery stenosis, pheochromocytoma or Cushing’s syndrome. 10. Diabetic subjects with an elevated glyco-hemoglobin level defined as HbA1c > 9.0% whether treated or not. 11. Subjects whose arm circumference (for the extremity to be used for the BP measurement) is 47 cm ( 19 inches). 12. A previous history of intolerance or hypersensitivity to the HMG-CoA reductase inhibitors and/or dihydropyridine CCBs, or to drugs with similar chemical structure. 13. Impaired hepatic function, as shown by but not limited to clinically significant or unexplained elevations of alanine aminotransferase (ALT, SGPT) or aspartate aminotransferase (AST, SGOT) > 2 times the upper limit of normal (ULN) for subjects who are statin-naïve. 14. An unexplained elevation in CPK (creatine phosphokinase) > 5 times upper limits of normal. 15. Fasting serum triglyceride concentration of =600 mg/dL (8.5 mmol/L). 16. Abnormal baseline findings considered by the Investigator to be indicative of conditions that might affect study results. 17. Any other condition, which in the Investigator’s judgment, might result in increased risk to the subject, would interfere with the conduct of the study or interpretation of the data or decrease the chance of obtaining satisfactory data to achieve the objectives of the study. 18. Participation in any other studies involving investigational or marketed products within 1 month prior to entry in the study. 19. Any condition rendering the subject unable to understand the nature or scope of the study and/or rendering the subject to be unable or unlikely to follow the protocol. 20. Significant alcohol and/or any other drug abuse within the last year. 21. Research site personnel. 22. Subjects on medication that are listed as prohibited medications in section 5.5. 23. Blood donors who will be giving blood during the study period and for 30 days after the last study visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether a Caduet®-based multi-factorial risk factor management strategy might result in greater reduction in total cardiovascular risk as compared with a usual care strategy after one year of treatment in subjects with hypertension and =3 additional risk factors, but no CHD and baseline total cholesterol (TC) =6.5 mmol/l (250 mg/dl).;Secondary Objective: The trial will evaluate a number of secondary endpoints as defined by the protocol.;Primary end point(s): The primary endpoint is the Month 12 Framingham 10-year risk. This endpoint will be analyzed using a mixed-effects analysis of variance (ANOVA) model. The model will include the baseline Framingham 10-year risk, age, country, gender, and treatment as the fixed effects and site as the random effect. The natural logarithm of the primary endpoint will be the dependent variable and a compound-symmetry (CS) covariance structure will be the covariance matrix for the subjects from the same site. Subjects from different sites will be assumed to be independent. This primary efficacy analysis will produce the following results: • The Type III 2-sided p-value of the treatment effect • The LS mean (LSM) • The 95% confidence interval • The estimated ICC A statistical superiority of the Caduet® arm over the Usual Care arm will be declared when the 2-sided p-value is less than 0.05. | — |
Countries
Czech Republic
Outcome results
None listed