Newly diagnosed and uncontrolled patients with essential arterial hypertension. MedDRA version: 20.0 Level: PT Classification code 10015488 Term: Essential hypertension System Organ Class: 10047065 - Vascular disorders
Conditions
Sponsors
Krka, d.d., Novo mesto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with essential arterial hypertension.* • Men and women aged = 18 years. • Written informed consent. • Ability to adhere to study protocol. *Additional inclusion criteria for Amlessa®: • Patients with essential arterial hypertension: o Naïve patients with systolic blood pressure (SBP) from 150 mmHg or higher AND/OR diastolic blood pressure (DBP) from 95 mmHg or higher (SBP = 150 AND/OR DBP = 90 mmHg for patients with type 2 diabetes mellitus) o Uncontrolled patients on antihypertensive monotherapy with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus). o Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus). *Additional inclusion criteria for Co-Amlessa®: • Patients with essential arterial hypertension (AH): o Uncontrolled patients on dual antihypertensive therapy (either in monoforms or FDC, including perindopril+amlodipine combination) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus). o Uncontrolled patients on triple antihypertensive therapy (either in monoforms or FDC) with SBP from 140 mmHg or higher AND/OR DBP from 90 mmHg or higher (SBP = 140 AND/OR DBP = 85 mmHg for patients with type 2 diabetes mellitus). 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 285 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 285
Exclusion criteria
Exclusion criteria: • History of adverse reactions or hypersensitivity associated with the use of the active substances, or any other components of the Investigational medicinal products (IMPs) used in the trial. • Hereditary/idiopathic angioedema. • Known secondary AH (e.g. pheochromocytoma, primary aldosteronism, renal artery stenosis) • Office measured Systolic blood pressure =200 mmHg • Unstable angina pectoris. • Acute heart failure and heart failure NYHA IV. • Antihypertensive drugs used for other indication than AH (e.g. tachyarrhythmia, glaucoma) less than 3 months before the study or in changed dosages less than 3 months before the study • Severe liver impairment OR biliary cirrhosis OR cholestasis OR hepatic encephalopathy • Renal dysfunction - GFR <60 ml/min (bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients with only 1 kidney, or post-renal transplant patients, dialysis patients • Any of the following clinically relevant laboratory or ECG findings - significant anaemia with haemoglobin less than 100 g/l, - serum AST and/or ALT and/or ALP and/or GammaGT of more than 3 x ULN (upper limit of normal) - hyperkalaemia (serum potassium of more than 5 mmol/l) - A-V block grade 2 or 3 - ECG signs of acute ischemia • Concurrent therapy with: o aliskiren-containing products (in patients with diabetes mellitus or renal impairment) o Lithium o Estramustine o Any “not allowed” medication(s) listed in Study protocol section 6.2 • Bradycardia with heart rate less than 50/min. • Female patients who are pregnant, planning to become pregnant. • Breastfeeding female patients. • Any significant acute condition (severe infection, exacerbation or uncontrolled phase of a chronic disease, major trauma, major surgery) within 30 days prior to screening visit. • Pathological clinical states (e.g. malignant diseases, excessive alcohol consumption, drug abuse or drug addiction, psychiatric conditions) or any life-threatening illness. • Patients currently participating in another clinical trial. • Patient’s refusal to participate with the investigator. • Normal average 24-hour SBP and DBP obtained by ABPM (<130/80 mmHg at baseline). • Severe orthostatic hypotension. • Patients to whom ß-blocker therapy cannot be discountinued in one day. • Previous or current therapy with perindopril and amlodipine and indapamide taken concomitantly all together as 3 separate tablets or as a fixed-dose combination. • In Amlessa® arm patients on previous or current therapy with perindopril and amlodipine taken concomitantly all together as 2 separate tablets or as a fixed-dose combination. (this exclusion criterion does not apply to Co-Amlessa® arm).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of the study is to establish the efficacy and safety of fixed-dose combination (FDC) of perindopril/amlodipine (Amlessa®) and fixed-dose combination of perindopril/indapamide/amlodipine (Co-Amlessa®) in wide populations of uncontrolled patients with arterial hypertension (AH) with special focus on effective continuous 24-hour blood pressure (BP) control. The purpose is also to establish the correlation between 24-hour central and peripheral BP.;Secondary Objective: Not applicable;Primary end point(s): Responder rate after 16 weeks (visit 5): proportion of patients reaching normal office blood pressure (NBP)*. * Normal (office) blood pressure (NBP): SBP < 140 mmHg and DBP < 90 mmHg; patients with type 2 diabetes mellitus: SBP < 140 mmHg and DBP < 85 mmHg);Timepoint(s) of evaluation of this end point: After 16 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Responder rate after 4 (visit 2), 8 (visit 3) and 12 weeks (visit 4): proportion of patients reaching office NBP*. o Mean absolute and relative change from baseline in office SBP and DBP after 4, 8, 12 and 16 weeks (Visit 2, 3, 4, 5). o Mean absolute and relative changes from baseline to 16 weeks in average 24-hour SBP and DBP, average awake time SBP and DBP, and average sleep time SBP and DBP, all obtained by ABPM. o Responder rate after 16 weeks (visit 5) in average 24-hour SBP and DBP, average awake time SBP and DBP, and average sleep time SBP and DBP, all obtained by ABPM: proportion of patients reaching normal average 24h ABPM SBP and DBP (<130/80), normal average awake time SBP and DBP (<135/85) and normal average sleep time SBP and DBP (<120/70). o Proportion of patients reaching a reduction of office SBP by at least 20 mmHg or DBP by at least 10 mmHg from baseline after 16 weeks. o Proportion of patients reaching a reduction of central (systolic) blood pressure parameters (in 24-hour measurement) below 120 mmHg from baseline after 16 weeks. o Proportion of patients reaching a reduction of pulse wave velocity (in 24-hour measurement) for at least 0,5 m/s from baseline after 16 weeks. o Proportion of patients reaching a reduction of SBP and DBP variability expressed as reduction of day-night standard deviation (SDdn) by at least 0.5 and that of average real variability (ARV) by at least 0.5.;Timepoint(s) of evaluation of this end point: After 4, 8, 12 and 16 weeks of treatment | — |
Countries
Armenia, Croatia, Hungary, Poland, Russian Federation, Serbia, Slovenia, Ukraine
Contacts
Public ContactClinical Trials Information
Krka, d.d., Novo mesto
Outcome results
None listed