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Moxonidine + Perindopril in Hypertensive Patients With Metabolic Syndrome (COMPOSER)

Primary Purpose

Arterial Hypertension, Metabolic Syndrome

Status

Unknown status

Phase

Phase 4

Locations

Russian Federation

Study Type

Interventional

Intervention

perindopril + moxonidine

About this trial

This is an interventional treatment trial for Arterial Hypertension focused on measuring perindopril, moxonidine

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients (male and female) aging 18 to 70 years.
Grade 1, 2 AH (SBP 140-179 mm Hg and/or DBP 90-109 mm Hg according 2018 ESH/ESC guidelines)
PWV > 10 m/s
Previous two-component antihypertensive therapy (ACEi/ARB+ diuretic (HCTZ or indapamide) or ACEI/ARB + amlodipine) during at least 6 months prior to the study enrollment
Metabolic syndrome diagnosed by the 2009 Russian Society of Cardiology (RSC) National Guidelines criteria
1. THE MAIN SIGN: central (abdominal) obesity defined as waist circumference (WC) above 80 cm in women and above 94 cm in men.
2. ADDITIONAL CRITERIA:
i. - arterial hypertension (BP ≥ 130/85 mm Hg) ii. - high triglycerides (≥ 1.7 mmol/l) iii. - decreased HDL-cholesterol (<1.0 mmol/l for men; <1.2 mmol/l for women) iv. - increased LDL-cholesterol > 3.0 mmol/l v. - fasting hyperglycaemia (fasting plasma glucose ≥ 6.1 mmol/l) vi. - impaired glucose tolerance (plasma glucose at 2 hours after glucose load from ≥7.8 to ≤11.1 mmol/l)
Metabolic syndrome is defined as presence of central obesity and two of the additional criteria.
Body Mass Index (BMI) >30 kg/m2.
For female patients with childbearing potential: negative pregnancy test and willingness to use reliable methods of contraception until the study treatment completion
Voluntarily signed informed consent to participate in the study.

Exclusion Criteria:

Contraindications for using ACEi and imidazoline receptor agonists.
Administration of perindopril or moxonidine during 6 months before the study onset.
Metformin therapy for prophylaxis diabetes mellitus type 2 in patients with pre-diabetes, which had been started within 6 months before the study enrollment. (If a patient receives metformin for a long time, i.e., more than 6 months, he/she can be included in the study, and metformin discontinuation is not required).
Statin and/or fibrate therapy started within 6 months before the study enrollment. (If a patient receives statins and/or fibrates for a long time, i.e., more than 6 months, he/she can be included in the study, and discontinuation of statins and fibrates is not required).
Current diagnosis of unstable angina, acute and subacute myocardial infarction.
Heart failure of any functional class.
Grade 3 AH (≥ 180/110 mm Hg).
Sinus bradycardia (heart rate ≤50/min).
Type 1 or 2 diabetes mellitus.
Severe comorbidities, including mental diseases.
Acute conditions (infections, exacerbation of chronic diseases, injuries, surgical interventions).
Alcohol abuse.
Pregnancy and lactation.
Serious renal dysfunction (Estimated Glomerular Filtration Rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) ≤30 ml/min/1.73 m2).
Serious hepatic dysfunction
Malignancies diagnosed and treated during the previous 5 years prior to study enrollment.
Inability to understand the study and to give informed consent for participation in it.

Sites / Locations

Dept. of Therapy and EndocrinologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

perindopril + moxonidine

Arm Description

perindopril 10 mg + moxonidine 0.4 or 0.6 mg a day (given as two divided doses).

Outcomes

Primary Outcome Measures

Change in Pulse wave velocity (PWV)

To assess the PWV after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Change in Central Blood Pressure (BP)

To assess the central BP changes (systolic BP, aortic pulse BP) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline levels.

Change in Reflected wave index

To assess the reflected wave index after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Secondary Outcome Measures

Change in carbohydrate and lipid metabolism parameters markers

To assess the homeostatic model assessment - insulin resistance (HOMA-IR), and lipid metabolism (total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL)) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline levels.

Change in the adipokine level

To assess the adipokine level (leptin) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Change in the Inflammatory marker level

To assess the high sensible C-reactive Protein (hs-CRP) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Change in the renin-angiotensin-aldosterone system hyperactivation marker level

To assess the renin-angiotensin-aldosterone system hyperactivation marker level (plasma aldosterone-to-renin ratio) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level

Change in the sympathoadrenal system hyperactivation marker levels

To assess the sympathoadrenal system hyperactivation marker levels (urine excretion adrenaline, noradrenaline, dofamine levels) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline levels.

Proportion of patients achieved target BP level

To assess the proportion of patients (%) achieving target BP levels <130/80 mm Hg at Week 4, Week 12, Week 24

Full Information

NCT ID

NCT04023565

First Posted

July 15, 2019

Last Updated

July 18, 2019

Sponsor

Sergey V. Nedogoda

1. Study Identification

Unique Protocol Identification Number

NCT04023565

Brief Title

Moxonidine + Perindopril in Hypertensive Patients With Metabolic Syndrome

Acronym

COMPOSER

Official Title

Open-Label Non-Comparative Study of the Effects of a Combination Antihypertensive Treatment With Moxonidine + Perindopril in Hypertensive Patients With Metabolic Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 11, 2019 (Actual)

Primary Completion Date

June 30, 2020 (Anticipated)

Study Completion Date

December 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sergey V. Nedogoda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The aim of study is to assess the angioprotective effects of antihypertensive combination therapy with perindopril 10 mg and moxonidine 0.4-0.6 mg in patients with arterial hypertension, metabolic syndrome, and obesity, who had Pulse Wave Velocity (PWV) > 10 m/s on the previously administered two-component combination antihypertensive therapy. Open-label non-comparative prospective study for 24 week for each patient.

Detailed Description

According to European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) Guidelines for the management of arterial hypertension 2018 in case of previous combination at full dose does not allow to achieve the target Blood Pressure (BP), that therapy might be switch to different two-drug combination. The study will enroll 120 hypertensive (Grade 1, 2 Arterial Hypertension (AH): Systolic Blood Pressure (SBP) 140-179 mm Hg and Diastolic Blood Pressure (DBP) 90-109 mm Hg According to ESC/ESH Guidelines 2018) patients with metabolic syndrome who met the inclusion criteria when treated with Angiotensin Converting Enzyme Inhibition(ACEi) /Angiotensin Receptor Blocker (ARB) + hydrochlorothiazide (HCTZ)/indapamide or +amlodipine (30 patients in each group): ACEi (except perindopril) + diuretic (HCTZ or indapamide) ACEi (except perindopril) + amlodipine ARB+ diuretic (HCTZ or indapamide) ARB+ amlodipine Upon obtaining Inform Consent the previous therapy will be discontinued according to recommendations (gradually or at once). After 14 days of wash-out period perindopril 10 mg + moxonidine 0.4 mg a day will be prescribed. If target BP is not achieved after 4 weeks, the dosage will increase up to perindopril 10 mg + moxonidine 0.6 mg a day (given as two divided doses). FORBIDDEN TREATMENTS: Any other antihypertensives (calcium antagonists, β-blockers, ACEi except perindopril, ARBs, diuretics) for routine AH management (except those used to resolve the uncontrolled hypertension). CRITERIA FOR PREMATURE PATIENT WITHDRAWAL FROM THE STUDY: Withdrawal of informed consent by the patient at any time of the study. Need for uncontrolled hypertension management occurring more than 2 times weekly throughout the 2 consecutive weeks during study period. Need for the third antihypertensive drug.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arterial Hypertension, Metabolic Syndrome

Keywords

perindopril, moxonidine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

perindopril + moxonidine

Arm Type

Experimental

Arm Description

perindopril 10 mg + moxonidine 0.4 or 0.6 mg a day (given as two divided doses).

Intervention Type

Drug

Intervention Name(s)

perindopril + moxonidine

Intervention Description

After 14 days of wash-out period perindopril 10 mg + moxonidine 0.4 mg a day will be prescribed. If target BP is achieved after 4 weeks, the dosage will remain unchanged (perindopril 10 mg + moxonidine 0.4 mg a day (given as two divided doses). If target BP is not achieved after 4 weeks, the dosage will increase up to perindopril 10 mg + moxonidine 0.6 mg a day (given as two divided doses).

Primary Outcome Measure Information:

Title

Change in Pulse wave velocity (PWV)

Description

To assess the PWV after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Time Frame

baseline and 24 weeks

Title

Change in Central Blood Pressure (BP)

Description

To assess the central BP changes (systolic BP, aortic pulse BP) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline levels.

Time Frame

baseline and 24 weeks

Title

Change in Reflected wave index

Description

To assess the reflected wave index after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Time Frame

baseline and 24 weeks

Secondary Outcome Measure Information:

Title

Change in carbohydrate and lipid metabolism parameters markers

Description

Time Frame

baseline and 24 weeks

Title

Change in the adipokine level

Description

To assess the adipokine level (leptin) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Time Frame

baseline and 24 weeks

Title

Change in the Inflammatory marker level

Description

To assess the high sensible C-reactive Protein (hs-CRP) after 24 weeks of combination treatment with perindopril 10 mg and moxonidine 0.4-0.6 mg against baseline level.

Time Frame

baseline and 24 weeks

Title

Change in the renin-angiotensin-aldosterone system hyperactivation marker level

Description

Time Frame

baseline and 24 weeks

Title

Change in the sympathoadrenal system hyperactivation marker levels

Description

Time Frame

baseline and 24 weeks

Title

Proportion of patients achieved target BP level

Description

To assess the proportion of patients (%) achieving target BP levels <130/80 mm Hg at Week 4, Week 12, Week 24

Time Frame

Week 4, Week 12, Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients (male and female) aging 18 to 70 years. Grade 1, 2 AH (SBP 140-179 mm Hg and/or DBP 90-109 mm Hg according 2018 ESH/ESC guidelines) PWV > 10 m/s Previous two-component antihypertensive therapy (ACEi/ARB+ diuretic (HCTZ or indapamide) or ACEI/ARB + amlodipine) during at least 6 months prior to the study enrollment Metabolic syndrome diagnosed by the 2009 Russian Society of Cardiology (RSC) National Guidelines criteria THE MAIN SIGN: central (abdominal) obesity defined as waist circumference (WC) above 80 cm in women and above 94 cm in men. ADDITIONAL CRITERIA: i. - arterial hypertension (BP ≥ 130/85 mm Hg) ii. - high triglycerides (≥ 1.7 mmol/l) iii. - decreased HDL-cholesterol (<1.0 mmol/l for men; <1.2 mmol/l for women) iv. - increased LDL-cholesterol > 3.0 mmol/l v. - fasting hyperglycaemia (fasting plasma glucose ≥ 6.1 mmol/l) vi. - impaired glucose tolerance (plasma glucose at 2 hours after glucose load from ≥7.8 to ≤11.1 mmol/l) Metabolic syndrome is defined as presence of central obesity and two of the additional criteria. Body Mass Index (BMI) >30 kg/m2. For female patients with childbearing potential: negative pregnancy test and willingness to use reliable methods of contraception until the study treatment completion Voluntarily signed informed consent to participate in the study. Exclusion Criteria: Contraindications for using ACEi and imidazoline receptor agonists. Administration of perindopril or moxonidine during 6 months before the study onset. Metformin therapy for prophylaxis diabetes mellitus type 2 in patients with pre-diabetes, which had been started within 6 months before the study enrollment. (If a patient receives metformin for a long time, i.e., more than 6 months, he/she can be included in the study, and metformin discontinuation is not required). Statin and/or fibrate therapy started within 6 months before the study enrollment. (If a patient receives statins and/or fibrates for a long time, i.e., more than 6 months, he/she can be included in the study, and discontinuation of statins and fibrates is not required). Current diagnosis of unstable angina, acute and subacute myocardial infarction. Heart failure of any functional class. Grade 3 AH (≥ 180/110 mm Hg). Sinus bradycardia (heart rate ≤50/min). Type 1 or 2 diabetes mellitus. Severe comorbidities, including mental diseases. Acute conditions (infections, exacerbation of chronic diseases, injuries, surgical interventions). Alcohol abuse. Pregnancy and lactation. Serious renal dysfunction (Estimated Glomerular Filtration Rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) ≤30 ml/min/1.73 m2). Serious hepatic dysfunction Malignancies diagnosed and treated during the previous 5 years prior to study enrollment. Inability to understand the study and to give informed consent for participation in it.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sergey V. Nedogoda, Professor

Phone

+79023643226

nedogodasv@rambler.ru

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sergey V. Nedogoda, Professor

Organizational Affiliation

Volgograd State Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dept. of Therapy and Endocrinology

City

Volgograd

ZIP/Postal Code

400131

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sergey V. Nedogoda, Professor

Phone

+79023643226

nedogodasv@rambler.ru

12. IPD Sharing Statement

Learn more about this trial

Moxonidine + Perindopril in Hypertensive Patients With Metabolic Syndrome

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