| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | 10015488 |
| E.1.2 | Term | Essential hypertension |
|
| 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 normalizing or reducing blood pressure in patients with essential hypertension not controlled by a previous monotherapy and with one ore more additional cardiovascular risk factors |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives are the assessment of efficacy on office systolic blood pressure and on ambulatory blood pressure, and on a marker of target organ damage such as left ventricular hypertrophy (LVH) quantified by calculation of the left ventricular mass index (LVMI) detected by echocardiography and electrocardiography (ECG), carotid intima-media thickness (IMT), renal function (creatinine clearance assessed by Cockroft-Gault formula) and subclinical renal damage (urinary albumin-creatinine ratio). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Outpatients aged 18-75 years
Male and female gender
Patients with essential hypertension currently taking one antihypertensive medication (ACE-inhibitor, AT1-antagonist, calcium-antagonist, diuretic or beta-blocker) in the last 3 months and not adequately controlled (office mean SBP ≥ 140 and/or DBP ≥ 90 mm Hg) 14
One or more additional cardiovascular risk factors among14:
- Smoking
- Total cholesterol >5.0 mmol/l (190 mg/dL) or on specific drug treatment
- LDL cholesterol >3.0 mmol/l (115 mg/dL) or on specific drug treatment
- HDL cholesterol <1.0 mmol/l (40 mg/dL) in males; <1.2 mmol/l (46 mg/dL) in females, or on specific drug treatment
- Fasting plasma glucose 5.6–6.9 mmol/l (102–125 mg/dL) or on specific drug treatment for hyperglycemia
- Diabetes mellitus: fasting plasma glucose &#8805; 7.0 mmol/l (126 mg/dL) or postload plasma glucose >11.0 mmol/l (198 mg/dL) or on specific drug treatment
- Abdominal obesity: waist circumference >102 cm in males; >88 cm females or BMI &#8805;25 and <30 kg/m2
- Family history of premature cardiovascular disease (males at age <55 years; females at age <65 years)
Able and willing to sign informed consent and to comply with study procedures
Written informed consent of the patient |
|
| E.4 | Principal exclusion criteria |
Malignant or secondary hypertension
Orthostatic hypotension (difference between mean sitting and standing SBP &#8805;20 mmHg)
Body mass index &#8805;30 kg/m2
Arm circumference <24 and >32 cm
Heart failure requiring medical treatment
Myocardial infarction in the 6 months prior to enrolment
Cerebrovascular events in the previous 6 months
Cardiogenic or septic shock
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 normal upper limit)*
Bilateral renal arterial stenosis, or unilateral for patients with a single kidney
Renal insufficiency (creatininemia >200 µmol/L or 2 mg/dL)*
Hypokalemia (<3.5 mEq/L) or hyperkalemia (>5.2 mEq/L) in at least two haematological examinations (if the patient presents at baseline hypo or hyperkalemia, this value has to be confirmed by a new examination to be performed during screening period)*
Severe concurrent pathology (cancer, AIDS, liver disease, etc.)
Females who are pregnant or lactating
Pre-menopausal woman who are of child-bearing potential and are not practicing acceptable methods of birth control, or DO NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include intrauterine device; oral, implantable or injectable contraceptives and surgical sterility.
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
Participation in other clinical trials in the previous one month
Conditions which in the investigator’s opinion may interfere with the study’s execution or due to which the patient should not participate for safety reasons
Risk of low patient cooperation |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage of subjects with office sitting blood pressure <140/90 mmHg (<130/80 mmHg in diabetics or patients with at least 3 risk factors) or with an office systolic blood pressure reduction of at least 20 mmHg or a sitting diastolic blood pressure reduction of at least 10 mmHg after 18 weeks of treatment (responders) (visit 3b – baseline) |
|
| 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 | No |
| 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 | 30 |
| E.8.5 | The trial involves multiple Member States | No |
| 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
| |
| 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 | 9 |
| 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 | 9 |
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