E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PATIENTS affected by METABOLIC SYNDROME WITH ESSENTIAL HYPERTENSION NOT CONTROLLED BY PREVIOUS MONOTHERAPY |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052066 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary study objective is to determine whether the combination zofenopril + hydrochlorothiazide is at least as effective as the irbesartan + hydrochlorothiazide combination in reducing office diastolic blood pressure in metabolic syndrome patients with essential hypertension not controlled by a previous monotherapy. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are the assessment of efficacy on office blood pressure and and on metabolic parameters (fasting blood glucose, HBA1C, triglycerides, HDL cholesterol, plasma insulin, insulin resistance -HOMA-IR-), waist circumference, and renal function (creatinine clearance assessed by Cockroft-Gault formula and albumin-creatinine ratio, microalbuminuria). In a subgroup of about 20% of study population/total randomised patients, in selected centres, the efficacy of the two drug on ambulatory blood pressure will be evaluated (24 hour, day-time, night-time, morning and last 6 hour ambulatory blood pressure averages, raise in morning blood pressure, smoothness index, Ambulatory Arterial Stiffness Index or AASI). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Outpatients aged &#8805; 18 years Caucasian males and females Diagnosis of essential hypertension according to Guidelines of European Society of Cardiology. Fasting plasma glucose &#8805; 100mg/dL or on drug treatment for elevated glucose One or more of the following criteria: 1) Waist circumference &#8805;102 cm in men and &#8805;88 cm in women 2) Serum triglycerides &#8805; 150 mg/dL or on drug treatment for elevated triglycerides* 3) HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women or on drug treatment for reduced HDL-C Continuous treatment with the same single antihypertensive drug (single active pharmaceutical ingredient) at least for 4 weeks before inclusion in the study Able and willing to sign informed consent and to comply with study procedures Written informed consent of the patient |
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E.4 | Principal exclusion criteria |
Serum level of HDL cholesterol < 35 mg/dL and/or Triglycerides > 1000 and/or LDL-C > 190 mg/dL Malignant or secondary hypertension Systolic isolated hypertension Orthostatic hypotension (difference between mean sitting and standing SBP &#8805; 20 mmHg) Heart failure requiring medical treatment Myocardial infarction in the 6 months prior to enrolment cerebrovascular events (including stroke or transient ischemic attack) in the previous 6 months Haemodynamically significant valvulopathy Hereditary/idiopathic angioedema History of angioedema associated with previous ACE-inhibitor therapy Liver pathology (AST or ALT > 3 times greater than normal upper limit or total serum bilirubin > 1.5 times greater than upper limit) Bilateral renal arterial stenosis, or unilateral for patients with a single kidney Renal insufficiency (creatininemia > 200 �mol/L or 2 mg/dL) Hypokalemia (< 3.5 mEq/L) or hyperkalemia (> 5.0 mEq/L) at least two haematological examinations (if the patient presents at baseline hypo or hyperkalemia, this value has to be confirmed either by a previous examination or by a new one within 3 days) Hyponatremia (< 136 mEq/L); Hypernatremia (Na > 145 mEq/L) Hypercalcemia: (serum Ca) + [(4 serum albumin) x 0,8] > 10,2 mg/dl Hyperuricemia (uric acid > 7 mg/dL) Patients receiving dialysis Hereditary galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorpion Severe concurrent other diseases (cancer, AIDS, liver disease, etc.) Positive history for renal transplantation Dementia, psychosis, alcoholism (> 350 g ethanol/week) or chronic abuse of medicines, drugs or psychoactive substances Introduction of concurrent therapies among those not permitted and which cannot be suspended without harm to the patient Hypersensitivity or contraindications to use of the product under study History of undesired side effects with ACE-inhibitors, AT1-antagonists or diuretics Current treatment with any antihypertensive agents that cannot be safely stopped (investigators decision) by the start of the run-in period Participation in other clinical trials in the previous 4 months Conditions which in the investigators opinion may interfere with the studys execution or due to which the patient should not participate for safety reasons Risk of low patient cooperation Females who are pregnant or lactating Females of childbearing potential not using adequate contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Office diastolic blood pressure change at study end (24 weeks baseline) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 34 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Ultima visita ultimo soggetto |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |