Efficacy and Safety of Perindopril 5 mg / Indapamide 1.25 mg / Amlodipine 5 mg Fixed Combination in Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of a fixed-dose combination of perindopril 5 mg /indapamide 1.25 mg / amlodipine 5 mg compared to the free combination of the same components (perindopril 4 mg / indapamide 1.25 mg in a single pill and amlodipine 5 mg pill given separately at the same time) in chinese patients with uncontrolled essential hypertension.

Official Title
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Evaluation of the Clinical Efficacy and Safety of Perindopril 5 mg / Indapamide 1.25 mg / Amlodipine 5 mg Fixed Combination in Single-pill After 2 Months of Treatment Versus Free Combination, Perindopril 4 mg / Indapamide 1.25 mg + Amlodipine 5 mg Given Separately at the Same Time, With Conditional Titration Based on Blood Pressure Control in Patients With Essential Hypertension Uncontrolled After 1 Month With Perindopril 4 mg / Indapamide 1.25 mg Bi-therapy.

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Fixed [Per/Ind/Aml]
* Drug: Free [Per/Ind + Aml]


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Men or women of Asian origin ≥18 years old Treated for essential hypertension Having the day of the selection visit an uncontrolled hypertension treated with any anti-hypertensive monotherapy at maximal dose or any dual therapy at starting dose according to investigator's routine practice or at least 1 month prior to the visit Having at the selection visit a sitting SBP≥140 and <180 mmHg and DBP≥90 and <110 mmHg Main Exclusion Criteria: Known or suspected symptomatic orthostatic hypotension or positive orthostatic test at the selection visit Treatment with more than 2 antihypertensive drugs or with 2 antihypertensive drugs at the highest doses at the selection visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed [Per/Ind/Aml]<br>From inclusion to Month 2, patients receive the fixed combination of perindopril 5 mg / indapamide 1.25 mg / amlodipine 5 mg (S06593). From Month 2 to 4, patients either stay at the same dose if the blood pressure is controlled, either are up-titrated to the next dose of the strategy if the blood pressure is not controlled (ie, perindopril 10 mg / indapamide 2.5 mg / amlodipine 5 mg). From Month 4 to 6, patients either stay at the same dose if the blood pressure is controlled, either are up-titrated to the next dose of the strategy if the blood pressure is not controlled (ie, for patients who were up-titrated at Month 2 visit: perindopril 10 mg / indapamide 2.5 mg / amlodipine 10 mg or for patients who were not yet up-titrated: perindopril 10 mg / indapamide 2.5 mg / amlodipine 5 mg. | Drug: Fixed [Per/Ind/Aml]<br>* Fixed Dose combination of Perindopril/Indapamide/Amlodipine<br>|
| Active Comparator: Free [Per/Ind + Aml]<br>From inclusion to Month 2, patients receive the free combination of perindopril 4 mg / indapamide 1.25 mg plus amlodipine 5 mg. From Month 2 to 4, patients either stay at the same dose if the blood pressure is controlled, either are up-titrated to the next dose of the strategy if the blood pressure is not controlled (ie, double dose of perindopril 4 mg / indapamide 1.25 mg plus amlodipine 5 mg for patients). From Month 4 to 6, patients either stay at the same dose if the blood pressure is controlled, either are up-titrated to the next dose of the strategy if the blood pressure is not controlled (ie for patients who were up-titrated at Month 2 visit: double dose of perindopril 4 mg / indapamide 1.25 mg plus double dose of amlodipine 5 mg or for patients who were not yet up-titrated:double dose of perindopril 4 mg / indapamide 1.25 mg plus amlodipine 5 mg. | Drug: Free [Per/Ind + Aml]<br>* Free dose combination of Perindopril/Indapamide and Amlodipine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitting SBP change after two months of treatment | Office sitting Systolic Blood Pressure (SBP) change from baseline to last post-baseline value over the period from Month 0 to month 2 | Baseline safety visit, Month 2 follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitting SBP change from month 2 to month 4 | Office sitting Systolic Blood Pressure (SBP) change from month 2 to month 4 | Month 2 follow-up visit, Month 4 follow-up visit | 
| Sitting SBP change from month 4 to month 6 | Office sitting Systolic Blood Pressure (SBP) change from month 4 to month 6 | Month 4 follow-up visit, Month 6 follow-up visit | 
| Sitting DBP change after two months of treatment | Office sitting Diastolic Blood Pressure (DBP) change from baseline to last post-baseline value over the period from Month 0 to month 2 | Baseline safety visit, Month 2 follow-up visit | 
| Sitting DBP change from month 2 to month 4 | Office sitting Diastolic Blood Pressure (DBP) change from month 2 to month 4 | Month 2 follow-up visit, Month 4 follow-up visit | 
| Sitting DBP change from month 4 to month 6 | Office sitting Diastolic Blood Pressure (DBP) change from month 4 to month 6 | Month 4 follow-up visit, Month 6 follow-up visit | 
| Sitting Mean Arterial Pressure change after two months of treatment | Sitting Mean Arterial Pressure (MAP) change from baseline to last post-baseline value over the period from Month 0 to month 2 with MAP=2/3 DBP+1/3 SBP | Baseline safety visit, Month 2 follow-up visit | 
| Sitting Mean Arterial Pressure change from month 2 to month 4 | Sitting Mean Arterial Pressure (MAP) change from from month 2 to month 4 , with MAP=2/3 DBP+1/3 SBP | Month 2 follow-up visit, Month 4 follow-up visit | 
| Sitting Mean Arterial Pressure change from month 4 to month 6 | Sitting Mean Arterial Pressure (MAP) change from from month 4 to month 6, with MAP=2/3 DBP+1/3 SBP | Month 4 follow-up visit, Month 6 follow-up visit | 
| Sitting Pulse Pressure change after two months of treatment | Sitting Pulse Pressure change from baseline to last post-baseline value over the period from Month 0 to month 2, with Pulse Pressure=SBP-DBP | Baseline safety visit, Month 2 follow-up visit | 
| Response to the treatment at two months | Number of patients responders, ie: with control of Blood Pressure : sitting SBP <140 mmHg and sitting DBP <90 mmHg) and/or sitting SBP decrease from baseline ≥20 mmHg or sitting DBP decrease from baseline ≥10 mmHg. | Month 2 follow-up visit | 
| Control of Blood Pressure at two months | Number of patients with Blood pressure controlled, ie : with sitting SBP <140 mmHg and sitting DBP < 90 mmHg | Month 2 follow-up visit | 
| Adverse events between Month 0 and Month 2 | Number experiencing treatment emergent adverse events between month 0 and month 2 | Up to the 2 month follow-up visit | 
| Adverse events between Month 0 and Month 6 | Number experiencing treatment emergent adverse events between month 0 and month 6 | Up to the 6 month final visit |