Effect of Atorvastatin on Carotid Intima Media Thickness

Evaluation of Carotid Intima Media Thickness by Treatment of Vascular and Metabolic Factors With Combined Antihypertensive and Hypolipidemic Therapy

The investigators hypothesize that additive effects of combined antihypertensive medications and statin in a single pill combination may better reduce progression of vascular remodeling and inhibit atherosclerosis progression. The fixed association of atorvastatin, perindopril and amlodipine under the name of Lipertance is the first fixed combination of these three groups to control the risk factors that are hypertension and dyslipidemia which can be used both in primary and secondary cardiovascular prevention .

Study Overview

• Status: Unknown
• Conditions: Hypercholesterolemia; Essential Hypertension
• Intervention / Treatment: Drug: Perindopril/Amlodipine and Perindopril/Amlodipine/Atorvastatin treatment

Detailed Description

Eligible participants with appropriately signed informed consent will be randomized to either the perindopril+amlodipin or perindopril+amlodipin+atorvastatin combinations.

Patients will be preliminary screened before 7-10 days for clinical and laboratory examination to meet eligibility criteria for inclusion in study.

Perindopril+amlodipine combination doses will be up titrated over two weeks in case of need to control adequate arterial blood pressure < 140/90. The 4 doses combinations and their adjustments will be made by investigating physician according to guideline based treatment of arterial hypertension and dyslipidemia.

Subjects should not previously be on statin therapy and subjects who needs to be will start atorvastatin in combination treatment pill . The investigators will study the effects of 6-month treatment with perindopril +amlodipin+atorvastatin combination on plasma concentrations of total cholesterol and LDL cholesterol. Liver enzyme markers will be assessed in patients on additional statin treatment on day 90 for safety assessment. All participants will be followed-up for 6 months.

Inclusion criteria

• Patients aged between 45 and 85 years
• blood pressure ≥ 140/90 mmHg with one antihypertensive drug or 150/100 mHg for untreated patients
• plasma LDL-cholesterol concentrations > 2,5mm/L (without concomitant hypolipidemic drugs)
• at least one additional cardiovascular risk factor apart of arterial hypertension
• minimal thickness of intima media complex at least 0,8 mm.

Exclusion criteria

• premenopausal females with potential for pregnancy
• angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker therapy in the previous 3 months,
• initiation or change in dose of statin therapy within previous 3 months
• anticipated change in lipid lowering therapy
• acute coronary or cerebrovascular event within 2 months
• glomerular filtration rate < 30 ml/min
• previous history of side effects to RAAS inhibitors and Ca channel blocking agents
• inability to give informed consent
• inability to undergo carotid ultrasound examination.

Adverse events (AE)

Based on the intention-to-treat the patient population, safety will be checked by recording adverse effects throughout the study: severe AEs regardless as to whether or not there is causal relationship between the AEs and the study; and relevant AEs such as myalgia, cough , palpitations, peripheric edemas, diziness symptoms. When the investigators confirm these AEs, the grade of severity, procedures, outcomes, and relationship to the study drug will be assessed and recorded.

Serious adverse event (SAE)

A serious adverse event is an AE occurring during any study phase and at any dose of the investigational product that fulfills one or more of the following criteria: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is an important medical event that may jeopardize the subject or may require medical intervention to prevent one of the outcomes listed above.

The Investigator must inform the Sponsor of any SAE that occurs in the course of the study within 48 hours of when he or she becomes aware of it.

Carotid Ultrasound An ultrasound linear probe with 5-10 MHz linear transducer will be used for measuring the carotid artery intima media thickness ( IMT ). The carotid artery will be scanned by 3 trained in vascular ultrasound and echocardiography physicians. All study subjects will be examined in the supine position with the head tilted backward. Measurements of the left and right IMT of the posterior wall of the common carotid, 1 cm distal to the bulb bifurcation, by ultrasound 2D exam will be performed

Blood pressure (BP) will be measured at the University Cardiology Clinic by a trained nurse or physician using a calibrated and validated digital sphygmomanometer. BP measurements will be taken with the patient in a seated position with the arm supported at heart level, after a 5 min rest and after abstaining from food, beverages containing caffeine, and smoking for at least 2 h prior to BP measurement. BP will be recorded as three serial measurements at intervals of 30 sec on both arms.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Patients aged between 45 and 85 years

  • blood pressure ≥ 140/90 mmHg with one antihypertensive drug or 150/100 mHg for untreated patients
  • plasma LDL-cholesterol concentrations > 4.1 mmol/L without hypolipidemic drugs within the last 6 months
  • at least one additional cardiovascular risk factor apart of arterial hypertension
  • minimal thickness of intima media complex at least 0,8 mm.

Exclusion Criteria:

• premenopausal females with potential for pregnancy
• angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker therapy in the previous 3 months,
• initiation or change in dose of statin therapy within previous 3 months
• anticipated change in lipid lowering therapy
• acute coronary or cerebrovascular event within 2 months
• glomerular filtration rate < 30 ml/min
• previous history of side effects to RAAS inhibitors and Ca channel blocking agents
• inability to give informed consent
• inability to undergo carotid ultrasound examination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Perindopril/Amlodipine arm; Patients will be preliminary screened before 7-10 days for clinical and laboratory examination to meet eligibility criteria for inclusion in study. Perindopril+amlodipine combination doses will be up titrated over two weeks in case of need to control adequate arterial blood pressure < 140/90. The 4 doses combinations and their adjustments will be made by investigating physician according to guideline based treatment of arterial hypertension and dyslipidemia.	Drug: Perindopril/Amlodipine and Perindopril/Amlodipine/Atorvastatin treatment; comparative antihypertensive antilipidemic treatment assessment on carotid intima media thickness in both study groups
Active Comparator: Perindopril/Amlodipine/Atorvastatin arm; Subjects should not previously be on statin therapy and subjects who needs to be will start atorvastatin in combination treatment pill . We will study the effects of 6-month treatment with perindopril +amlodipin+atorvastatin combination on plasma concentrations of total cholesterol and LDL cholesterol.	Drug: Perindopril/Amlodipine and Perindopril/Amlodipine/Atorvastatin treatment; comparative antihypertensive antilipidemic treatment assessment on carotid intima media thickness in both study groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in mean IMT of the CCA from baseline to 6 months in two groups and antihypertensive treatment efficacy in both groups .	The fixed association of atorvastatin, perindopril and amlodipine is the first fixed combination of these three groups to control the risk factors that are hypertension and dyslipidemia. Additive effects of combined antihypertensive medications and statin in a single pill combination may better reduce progression of vascular remodeling and inhibit atherosclerosis progression.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of level of total and LDL cholesterol concentrations in blood plasma after 6 months of treatment in both groups.	Assessment of level of total and LDL cholesterol concentrations in blood plasma after 6 months of treatment in both groups and correlation between carotid IMT and values of total cholesterol and LDL levels in blood plasma.	6 months

Collaborators and Investigators

• Sponsor: Yerevan State Medical University
• Collaborators: Servier
• Investigators: Principal Investigator: Hamayak Sisakian, MD, Yerevan State Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2020
• Primary Completion (Anticipated): October 16, 2020
• Study Completion (Anticipated): February 28, 2021

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: March 10, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: arterial hypertension; statin; carotid artery intima-media thickness
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertension; Hypercholesterolemia; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Atorvastatin; Amlodipine; Perindopril; Amlodipine, atorvastatin drug combination
• Other Study ID Numbers: YerevanStateMU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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