Evaluation of the Clinical Efficacy and Safety of Amlodipine 5mg/ Bisoprolol Fumarate 5mg /Perindopril Arginine 5mg Fixed-dose Combination in Capsule and Free Monotherapy at the Same Dose in Patients With Uncontrolled Essential Hypertension.

NCT ID: NCT05288400

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-14
• Study Completion Date: 2018-12-18

Brief Summary

The purpose of this study was to evaluate the efficacy and the safety of a fixed-dose combination in capsule of Amlodipine 5mg/ Bisoprolol fumarate 5mg/ Perindopril arginine 5mg, and free monotherapy at the same dose in patients with uncontrolled essential hypertension.

Detailed Description

This was a phase III, multicenter, randomized, open-label, controlled study, over a 12-week treatment period with a single-capsule of fixed dose combination (FDC) of Amlodipine 5 mg/ Bisoprolol fumarate 5 mg / Perindopril arginine 5 mg and free monocomponents of Amlodipine 5 mg, Bisoprolol fumarate 5 mg and Perindopril arginine 5 mg given concomitantly, in 150 patients with uncontrolled essential HT.

Patients without any non-selection criteria, already treated by anti-hypertensive monotherapy at maximal dose or either by a dual therapy at minimum dose, other than study treatment, having an uncontrolled HT defined by SBP (Systolic Blood Pressure) ≥ 140 and <160 mmHg and DBP (Diastolic Blood Pressure) ≥ 90 and <100 mmHg (in supine position) at 2 different visits (selection and inclusion) were to be selected in this study and randomized to one of two treatment groups: single-capsule combination or free therapy without any wash-out period.

For all patients, controlled blood pressure (BP) was defined as SBP < 140 mmHg and DBP < 90 mmHg.

Conditions

Essential Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

single-capsule of fixed dosed combination (FDC) of amlodipine 5 mg / bisoprolol fumarate 5 mg / perindopril arginine 5 mg

Group Type: EXPERIMENTAL

Amlodipine 5mg + bisoprolol fumarate 5mg + perindopril arginine 5mg

Intervention Type: COMBINATION_PRODUCT

1 capsule/day Oral administration

Group B

Free triple therapy of amlodipine 5 mg + bisoprolol fumarate 5 mg + perindopril arginine 5 mg, given concomitantly

Group Type: ACTIVE_COMPARATOR

Norvasc 5mg tablet

Intervention Type: DRUG

Norvasc (amlodipine) 5mg, 1 tablet/day

Concor 5mg tablet

Intervention Type: DRUG

Concor (bisoprolol fumarate) 5mg, 1 tablet/day

Coversyl 5mg tablet

Intervention Type: DRUG

Coversyl (perindopril arginine) 5mg, 1 tablet/day

Interventions

Amlodipine 5mg + bisoprolol fumarate 5mg + perindopril arginine 5mg

1 capsule/day Oral administration

Intervention Type: COMBINATION_PRODUCT

Norvasc 5mg tablet

Norvasc (amlodipine) 5mg, 1 tablet/day

Intervention Type: DRUG

Concor 5mg tablet

Concor (bisoprolol fumarate) 5mg, 1 tablet/day

Intervention Type: DRUG

Coversyl 5mg tablet

Coversyl (perindopril arginine) 5mg, 1 tablet/day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Drugs contraindicated with the study treatments as defined in the Summaries of Product Characteristics of each study drugs

Concerning contra-indications to treatment with amlodipine, bisoprolol or perindopril

• Any history of angioedema, hereditary, idiopathic or associated with previous ACE inhibitor therapy.
• Allergy / hypersensitivity / history of intolerance or any contra-indications related to:

• amlodipine or any other dihydropyridine and calcium inhibitors;
• perindopril or any other ACE inhibitor;
• bisoprolol or other beta-blockers;
• any of the excipients of the study drugs.

• Respect of the previous selection and non-selection criteria.
• Confirmed essential uncontrolled HT under patient's current treatment at W000 visit, defined as SBP ≥140 and < 160 mmHg and DBP ≥90 and < 100 mmHg, measured with a validated automatic device in supine position after at least 10 minutes of rest. There were 3 BP measurements at 2-3 minutes of an interval between each measurement. The mean of the two last values of the three measurements was taken.
• Normal or without any clinically significant abnormality 12-lead ECG (left ventricular hypertrophy and post-MI ECG-changes are authorized at selection and during the study).
• Normal or without clinically significant abnormality of laboratory examinations. Microalbuminuria was authorized.

• As per non-selection criteria.
• Occurrence of an event requiring immediate notification since Selection.
• Laboratory results unavailable at the inclusion visit.
• Withdrawal of informed consent by patient.
• DBP ≥100 mmHg and/or SBP ≥160 mmHg under treatment since the selection visit.
• Positive orthostatic test at inclusion.
• Positive β-human Chorionic Gonadotrophin (β-HCG) pregnancy test (Blood test).
• Laboratory results unavailable at the inclusion visit or clinically significant abnormalities. Macroalbuminuria (>300 mg albumin/24h) was not authorized. ASpartate (Amino)Transferase (ASAT) or ALanine (Amino)Transferase (ALAT) ≥ 2 UNL (Upper Normal Limit) was not authorized.

Exclusion Criteria

• Patients whose BP was still uncontrolled at two consecutive visits (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) or whose SBP/DBP was above 160/100 mmHg (confirmed with 2 consecutive visits starting W004, at least 14 days apart).
• Onset of an adverse event (AE) which required prescription of a treatment incompatible with the protocol.
• Onset of an AE which, according to the investigator, makes it unsafe for the patient to continue with the study treatment. This includes clinically significant abnormal biochemical and haematological parameters, or clinically significant ECG abnormality.
• Pregnancy.
• Major protocol deviation preventing the analysis of the main endpoint, or which, in the opinion of the investigator, makes it unsafe for the patient to continue to take the study medication and to stay in the study.
• Non-medical reason (patient's personal decision to stop treatment).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Servier

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra Konradi

Role: PRINCIPAL_INVESTIGATOR

Almazov National Medical Research Centre - Department of Hypertension, Saint Petersburg, Russia

Locations

Regional state budget health care institution "Altai Regional Cardiological dispensary" 46 Malakhova St.

Barnaul, Altayskiy Kray, Russia

Problems of Cardiovascular Diseases" 6 Sosnovy Bulvar St.

Kemerovo, , Russia

Autonomous non-profit organization "Medical Center "Alliance" 12 Molodezhnaya St., 12

Kirovsk, , Russia

State budgetary healthcare institution of city of Moscow "City polyclinic #2 of Healthcare Department of city of Moscow" 12 Fruktovaya St.

Moscow, , Russia

Federal State Budgetary Institution ''Ourpatient clinic #5'' of the Administration of the President of the Russian Federation 14 Plyushchikha St.

Moscow, , Russia

St. Petersburg State Budgetary Healthcare Institution "The city hospital No.38. named after N.A. Semashko" 7/2 letter A Gospitalnaya Str., Pushkin

Saint Pertersburg, , Russia

Pavlov First Saint Petersburg State Medical University L'va Tolstogo str. 6-8

Saint Pertersburg, , Russia

LLC "Medicinskie tekhnologii", Nevzorova street, 6/191025, Saint-Petersburg, Vosstania street, 8 lit A

Saint Petersburg, , Russia

LLC "Strategicheskie Medicinskie Sistemy", Nevzorova street, 6

Saint Petersburg, , Russia

Saint-Petersburg State Budgetary Healthcare Institution "City outpatient clinic №109" 8 bld. 2 Oleko Dundicha

Saint Petersburg, , Russia

Limited Liability Company "Medical Research Institute" 25 Let. A 3 Kolya Tomchak St.

Saint Petersburg, , Russia

Federal State Budgetary Institution "North-West Federal Medical Research Center n.a. V.A. Almazov" of the Ministry of Health of the Russian Federation 2 Akkuratova St.

Saint Petersburg, , Russia

The Federal State Budgetary Institute "The Nikiforov Russian Center of Emergency and Radiation Medicine" The Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters

Saint Petersburg, , Russia

St. Petersburg State Budgetary Healthcare Institution "City Consulting and Diagnostic Center No. 85" 89 bld. 3 Let. A Prospekt Veteranov

Saint Petersburg, , Russia

Limited Liability Company "MART" 54 bld. 3 Let. J Maly Prospekt V.O

Saint Petersburg, , Russia

Countries

Russia

Other Identifiers

CL3-05166-003

Identifier Type: -

Identifier Source: org_study_id