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

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Fixed [Per/Ind/Aml]; Drug: Free [Per/Ind + Aml]

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China
      • Xuanwu Hospital Capital Medical Universtiy
  • Chongqing
    • Chongqing, Chongqing, China
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China
      • The First Affiliated Hospital Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
    • Fuzhou, Fujian, China
      • The First Affiliated Hospital Of Fujian Medical University
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou university second hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The First Affiliated Hospital Of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • The First Affiliated Hosptial of Baotou Medical college, Innter Mongolia University of Science & Technology
    • Hohhot, Inner Mongolia, China
      • Inner Mongolia People's Hospital
  • Jiangshu
    • Xuzhou, Jiangshu, China
      • The Affiliated Hospital of Xuzhou Medical College
    • Xuzhou, Jiangshu, China
      • Xuzhou Central Hospital
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The Second Affiliated Hospital of Soochow University
    • Wuxi, Jiangsu, China
      • Wuxi Second People's Hospital
    • Yangzhou, Jiangsu, China
      • Yangzhou First People's Hospital
    • Yangzhou, Jiangsu, China
      • Northern Jiangsu People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Bethune Hospital of Jilin University
    • Changchun, Jilin, China
      • Jilin university China-Japan Union Hospital
  • Liaonig
    • Daqing, Liaonig, China
      • Daqing Oilfield General Hospital
  • Liaoning
    • Dalian, Liaoning, China
      • First Affiliated Hospital of Dalian Medical University
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • The People's Hospital of Liaoning Province
  • Nanjing
    • Nanjing, Nanjing, China
      • The Affiliated Jiangning Hospital of Nanjing Medical University
  • Qinghai
    • Xining, Qinghai, China
      • Qinghai Provincial People's Hospital
  • Shandong
    • Jinan, Shandong, China
      • Shandong Provincial Qianfoshan Hospita
    • Linyi, Shandong, China
      • Linyi People's Hospital
    • Zaozhuang, Shandong, China
      • Zaozhuang Municipal Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital affiliated to Shanghai Jiaotong University
  • Shanxi
    • Taiyuan, Shanxi, China
      • The First Hospital of Shanxi Medical University
    • Xi'an, Shanxi, China
      • The First Affiliated Hospital, School of Medicine of Xi'an Jiaotong University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China
      • Tianjin People's Hospital
  • Uyghur Autonomous Region
    • Ürümqi, Uyghur Autonomous Region, China
      • People's Hospital of Xinjiang Uyghur Autonomous Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed [Per/Ind/Aml]; 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]; Fixed Dose combination of Perindopril/Indapamide/Amlodipine
Active Comparator: Free [Per/Ind + Aml]; 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]; Free dose combination of Perindopril/Indapamide and Amlodipine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Actual): February 23, 2022
• Study Completion (Actual): February 23, 2022

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CL3-6593-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1st January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No