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

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



Sponsors


Source

Centro Universitario de Ciencias de la Salud, Mexico

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

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.

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.

Overall Status

Recruiting

Start Date

2018-08-06

Completion Date

2019-06-14

Primary Completion Date

2019-01-15

Phase

Phase 4

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Pulse Wave Velocity (PWVao)
56 days

Secondary Outcome

Measure

Time Frame

Peripheral vascular resistance
56 days
Cardiac output
56 days
Pulse Pressure (PP)
56 days
Augmentation Index (AIx)
56 days
Systolic blood pressure
56 days
Diastolic blood pressure
56 days
Creatinine
56 days

Enrollment

28

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

Losartan and amlodipine in fixed combination capsules, 100mg/5mg. One time daily with the first bite of eat meal per 8 weeks

Arm Group Label

losartan and amlodipine

Other Name

Bicartial


Intervention Type

Drug

Intervention Name


Description

Losartan capsules, 100mg. One time daily with the first bite of eat meal per 8 weeks

Arm Group Label

Losartan



Eligibility

Criteria

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)

Gender

All

Minimum Age

40 Years

Maximum Age

65 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Fernando Grover Paez, PhD
Principal Investigator
Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Overall Contact

Last Name

Fernando Grover Paez, PhD

Phone

3310585200

Phone Ext

33642

Email



Location

Facility

Status

Contact

Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara
Guadalajara Jalisco 44340 Mexico
Recruiting
Last Name: Fernando Grover Paez, PhD
Phone: 3310585200
Phone Ext: 33642
Email: [email protected]

Location Countries

Country

Mexico


Verification Date

2018-08-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Centro Universitario de Ciencias de la Salud, Mexico

Investigator Full Name

Fernando Grover Paez

Investigator Title

Principal Investigator


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Amlodipine

Losartan



Arm Group

Arm Group Label

losartan and amlodipine

Arm Group Type

Other

Description

Individuals with SAH grade 1 or 2 without triple pharmacological therapy.


Arm Group Label

Losartan

Arm Group Type

Active Comparator

Description

Individuals with SAH grade 1 or 2 without triple pharmacological therapy.



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Fernando Grover Paez, PhD

Phone

3310585200

Phone Ext

33642

Email



Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Intervention Model Description

assignment

Primary Purpose

Treatment

Masking

Double (Participant, Investigator)

Masking Description

double blind (subject, investigator)


Study First Submitted

August 8, 2018

Study First Submitted Qc

August 9, 2018

Study First Posted

August 10, 2018

Last Update Submitted

August 15, 2018

Last Update Submitted Qc

August 15, 2018

Last Update Posted

August 17, 2018


ClinicalTrials.gov processed this data on August 27, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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