Losartan/Amlodipine on Hemodynamics Parameters and Arterial Stiffness in Arterial Hypertension

Effect of the Administration of Losartan / Amlodipine in Fixed Combination Versus Losartan on Hemodynamic and Arterial Stiffness Parameters in Patients With Systemic Hypertension Grade 1 and 2

Systemic Arterial Hypertension (SAH) is a disease with a high prevalence in Mexico and worldwide. SAH is associated with an increase in cardiovascular morbidity and mortality, causing cardiovascular disease (CVD), heart failure (HF), as well as chronic kidney disease (CKD). Several of the physiopathological mechanisms observed are: the increase in cardiac output, central aortic pressure (CAP), pulse wave velocity (PWV) and peripheral vascular resistance (PVR), which leads to the generation of damage to the target organ. The identification not only of the peripheral arterial pressure, but also of these hemodynamic parameters and arterial stiffness would allow a better cardiovascular characterization of the patients. However, the measurements of hemodynamic parameters and arterial stiffness can vary during the 24 hours from individual to individual by all known mechanisms involved in the regulation of blood pressure such as cortisol, central nervous system, the peripheral nervous system, along with the renin angiotensin and aldosterone system, which are usually only measured in a single moment. Generally, the choice of drug in a patient with SAH is based only on the values of peripheral blood pressure at the time of the measurement. The use of oscillometric equipment such as the Mobil-O-Graph 24 allows to the investigators to know the hemodynamic and arterial stiffness behavior during 24 hours; therefore, this could favor the choice of the most appropriate antihypertensive drug, dose and administration time. The use of angiotensin II receptor antagonists (ARA II) At1 blockers such as losartan and calcium channel blockers (CCB) for instance amlodipine have shown a reduction in CAP and peripheral blood pressure respectively in patients with SAH. The most prescribed drugs in health units worldwide are enalapril, amlodipine, losartan and atenolol, of which the most used combination is losartan with amlodipine. There are no studies to date that allow investigators to identify the effect of the administration of losartan / amlodipine in a fixed combination form on the hemodynamic parameters and arterial stiffness of patients with SAH. Therefore, the objective of the present study is to evaluate the effect of this fixed combination versus losartan on hemodynamic and arterial stiffness parameters based on the behavior of these for 24 hours.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Drug: Losartan and Amlodipine; Drug: Losartan

Detailed Description

In the present investigation the investigators expect to know the effect of the administration of losartan / amlodipine in fixed combination versus losartan on hemodynamic parameters and arterial stiffness in patients with arterial hypertension grade 1 and 2. For this purpose the investigators will conduct a double-blind randomized trial, each group will be compose by 14 male and female patients, 40-65 years old, with hypertension, neither with diabetes nor being under triple pharmacological therapy. Randomization will determine who will receive the intervention during an 8- week trial (losartan/amlodipine in fixed combination capsule, 100mg/5mg 1 time daily or losartan capsule 100mg 1 time daily). The clinical findings and laboratory tests include a metabolic profile and biosafety, which will be at baseline and by the 8th week . Body weight, body fat, body mass index (BMI) and blood pressure will be determined during the initial and final visit, in addition to hemodynamics parameters of arterial stiffness like cardiac output, central aortic pressure (CAP), pulse wave velocity (PWV) and peripheral vascular resistance (PVR) by an oscillometric monitoring system via Mobil-O -Graph® 24. Adverse events and adherence to treatment will be documented. Statistical analysis: Mann-Whitney U Test and Wilcoxon exact test. It is considered with significance at p<0.05.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Recruiting
      • Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara
      • Contact: Fernando Grover Paez, PhD; Phone Number: 33642 3310585200; Email: fgroverp@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of hypertension grade 1 or 2 according to the criteria of the American Heart Association (2017)
• Written informed consent
• Patients who are undergoing antihypertensive treatment and who, at the trial of the investigator and taking care of the health and safety of the patient, can undergo at least 2 weeks of washing prior to the visit of day 0 (it will be evaluated on a case-by-case basis).

Exclusion Criteria:

• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥120 mmHg
• Diabetes Mellitus
• Treated with triple pharmacological therapy
• Untreated thyroid disease
• Total cholesterol >400mg/dl
• Triglycerides >400mg/dl
• Liver enzymes (alt and ast) more tan twice the normal range
• Glomerular filtration rate <60ml/min (Cockcroft-Gault)

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
Other: losartan and amlodipine; Individuals with SAH grade 1 or 2 without triple pharmacological therapy.	Drug: Losartan and Amlodipine; Losartan and amlodipine in fixed combination capsules, 100mg/5mg. One time daily with the first bite of eat meal per 8 weeks; Other Names: Bicartial
Active Comparator: Losartan; Individuals with SAH grade 1 or 2 without triple pharmacological therapy.	Drug: Losartan; Losartan capsules, 100mg. One time daily with the first bite of eat meal per 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse Wave Velocity (PWVao)	Before and after intervention with oscillometric monitoring system via Mobil-O -Graph® 24. Maximum score 12 m/s	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral vascular resistance	Before and after intervention with oscillometric monitoring system via via Mobil-O -Graph®. Maximum score 1.8s*mmHg/ml	56 days
Cardiac output	Before and after intervention with oscillometric monitoring system via via Mobil-O -Graph®. Maximum score 6.5L/min	56 days
Pulse Pressure (PP)	Before and after intervention with oscillometric monitoring system via via Mobil-O -Graph® 24. Maximun score <75 mmHg	56 days
Augmentation Index (AIx)	Before and after intervention with oscillometric monitoring system via via Mobil-O -Graph® 24. Maximum score 110%	56 days
Systolic blood pressure	Before and after intervention using a digital manometer. Maximum score 160 mmHg	56 days
Diastolic blood pressure	Before and after intervention using a digital manometer. Maximum score 100 mmHg	56 days
Creatinine	Before and after intervention by spectrophotometry. Maximum score 1.3 mg/dl	56 days

Collaborators and Investigators

• Sponsor: Centro Universitario de Ciencias de la Salud, Mexico
• Investigators: Principal Investigator: Fernando Grover Paez, PhD, Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2018
• Primary Completion (Anticipated): January 15, 2019
• Study Completion (Anticipated): June 14, 2019

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: hypertension; arterial stiffness; losartan/amlodipine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Losartan
• Other Study ID Numbers: CUCS-INTEC-MV-LOAM-001

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