Management of Newly Diagnosed and Uncontrolled Hypertension With Fixed-Dose Combination of Perindopril/Amlodipine and Perindopril/Indapamide/Amlodipine

• Status: Completed
• Trial end date: 2019-09-27
• Target enrollment: 0
• Participant gender: All

Summary

PRECIOUS Study aims to evaluate the efficacy and safety of therapy with fixed-dose combination (FDC) of perindopril/amlodipine (Amlessa®) and FDC of perindopril/indapamide/amlodipine (Co-Amlessa®) on blood pressure reduction in both previously untreated patients and patients with previous antihypertensive therapy.

Adult patients with AH who are treatment-naïve with systolic blood pressure (SBP) from 150 mmHg or higher AND/OR diastolic blood pressure (DBP) from 95 mmHg or higher (SBP ≥ 150 mm AND/OR DBP ≥ 90 mmHg for patients with type 2 diabetes mellitus ) and uncontrolled patients on mono, dual or triple antihypertensive therapy with systolic blood pressure (SBP) from 140 mmHg or higher AND/OR diastolic blood pressure (DBP) from 90 mmHg or higher (SBP ≥ 140 AND/OR DBP ≥ 85 mmHg for patients with type 2 diabetes mellitus) will be invited to participate in this study.

During 16-week trial, seven study visits are planned. At first study visit physical examination, medical history, BP measurement, electrocardiogram (ECG), laboratory analysis and of Ambulatory Blood Pressure Measurement (ABPM) will be performed. Based on their previous antihypertensive therapy, patients will receive to treatment with either Amlessa® or Co-Amlessa® for the duration of 16 weeks and blood pressure measurements, laboratory investigations and patient interviews will be performed at study follow-up visits to assess the treatment efficacy (proportion of patients reaching normal office blood pressure after 16 weeks of treatment) and safety.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: KRKA
• Collaborators: Clinres Farmacija d.o.o.; University Medical Centre Ljubljana
• Treatments: Amlodipine; Antihypertensive Agents; Indapamide; Perindopril

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:

• 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)

• 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).

• 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):

• 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).

• 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).

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 New York Heart Association (NYHA) Class 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 - glomerular filtration rate (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 aspartate transaminase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) and/or gamma-glutamyltransferase (GGT) of more than 3 x upper limit of normal (ULN)

• hyperkalaemia (serum potassium of more than 5 mmol/l)

• A-V block grade 2 or 3

• ECG signs of acute ischemia

• Concurrent therapy with:

• aliskiren-containing products (in patients with diabetes mellitus or renal impairment)

• Other antihypertensive drugs or other medications that may cause hypotension:

exception are antihypertensive drugs used for other indication than AH (e.g. tachyarrhythmia, glaucoma) introduced more than 3 months before the study or in changed dosages more than 3 months before the study

• Drugs that may produce an increase in blood pressure: systemic corticosteroids, hormonal medications (chronically used oral contraceptives are allowed), adrenergic receptor agonists, cyclosporine, erythropoietin, migraine medications such as triptans and ergotamines

• Agents with important interactions with perindopril or to any other ACE inhibitor, to indapamide or to any other sulphonamides, to amlodipine or to dihydropyridine derivatives: lithium, estramustine

• Agents that may interfere with amlodipine hepatic metabolism (CYP3A4): protease inhibitors, rifampicin, macrolides like erythromycin or clarithromycin, azole antifungals like ketoconazole and itraconazole, Hypericum perforatum.

• Medications contraindicated in uncontrolled arterial hypertension:

anticoagulants, thrombolytics.

• 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 Ambulatory Blood Pressure Measurement (ABPM) device (<130/80 mmHg) at baseline.

• Severe orthostatic hypotension.

• Patients to whom β-blocker therapy cannot be discontinued in one day.

• Previous or current therapy with perindopril and amlodipine and indapamide taken 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).