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Atorvastatin Effects On Arterial Stiffness In Hemodialysis

Sponsor
Alexandria University (Other)
Overall Status
Completed
CT.gov ID
NCT04472637
Collaborator
(none)
50
Enrollment
1
Location
2
Arms
8
Actual Duration (Months)
6.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research aims to assess effects of atorvastatin on arterial stiffness in hemodialysis patients

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among patients with end-stage renal disease (ESRD) on hemodialysis (HD).

CVD are present since the early stages of chronic kidney disease (CKD) and reach around 30 to 44% of those beginning hemodialysis. Macrovascular disease develops rapidly in uremic patients and is responsible for the high incidence of ischemic heart disease, left ventricular (LV) hypertrophy, congestive heart failure, sudden death, and stroke.

Compared with the general population, the incidence of cardiovascular (CV) events among patients with ESRD is significantly higher, but it does not seem to be fully explained by the increased incidence of conventional risk factors alone. It has been hypothesized that HD patients are exposed to unique renal and HD-related risk factors that predispose them to an increased rate of CV events. Research efforts have expanded understanding of the contribution made by vascular pathologies to this burden.

Clinicians now recognize that defects in the vascular wall are the bases of many CV events, and early detection and intervention in subclinical vascular disease are fundamental for preventing and controlling cardiovascular events. Changes in the vasculature include endothelial dysfunction (ED), smooth muscle cell hyperplasia/hypertrophy, vascular calcification, and arterial stiffness.

Arterial stiffness is one of the vascular pathologies in HD patients. Recent studies examining cardiovascular complications in dialysis patients focused on atherosclerosis, including arterial stiffness and wall thickness changes as a major contributing factors for CV events. It was shown that stiffening of arteries is associated with increased cardiovascular mortality and morbidity.

Arteriosclerosis refers to the reduced arterial compliance due to increased fibrosis, loss of elasticity, and vessel wall calcification affecting the media of large and middle-sized arteries. These arterial wall changes are influenced not only by nonspecific factors, such as age, genetics, hypertension, diabetes, lipid abnormalities, inflammation, and/or common atherosclerosis, but also by parameter(s) associated with the presence of uremia per se.

Arterial stiffening in patients with CKD and ESRD occurs at an accelerated rate compared with the normal ageing process and arteriosclerosis. As bone mineral metabolism worsens with advancement to ESRD, hyperphosphatemia, secondary hyperparathyroidism and inhibited vitamin D synthesis result in vascular calcification that causes hardening of the arteries. Other factors linked to the uremic environment, such as anaemia, endothelial dysfunction, neuro-hormonal activation and inflammation, play important roles.

Arterial stiffness can be assessed noninvasively with the use of pulse wave velocity (PWV) measurement. The aortic pulse wave velocity (APWV) reflects central arterial stiffness. APWV is a predictor of cardiovascular outcome in patients with hypertension, diabetes, end-stage renal disease, and elderly hospitalized subjects.

Statins or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are considered first-line treatment for elevated low-density lipoprotein cholesterol (LDL-C) levels, as large-scale, randomized clinical trials have demonstrated their clinical benefits in primary and secondary prevention of cardiovascular events. Background and clinical studies have also shown beneficial actions of statins for the vasculature that may extend above their lipid lowering properties, such as improvement of endothelial function, inhibition of vascular smooth muscle cell proliferation, and reduction of vascular inflammation. It has been also proposed that such pleiotropic effects of statins may translate into a beneficial impact on arterial stiffness. Atorvastatin reduced arterial stiffness in patients with hypertension and hypercholesterolemia, diabetes mellitus. Fassett at al. found that atorvastatin reduced arterial stiffness in CKD patients (stage 2-4) but they did not include patients on maintenance haemodialysis in their study. We want to illustrate if these beneficial effects on arterial stiffness will be present or not among haemodialysis patients.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This research is a double-blinded , placebo-controlled, randomized clinical trial. Fifty patients with end-stage renal disease (ESRD) receiving hemodialysis treatment will be enrolled in the study. Patients will be randomly assigned using block randomization method into two study groups: Experimental group (25 patients): They will receive atorvastatin 10 mg, as one tablet /day for 24 weeks. Control group (25 patients): They will receive a placebo in the form of multivitamin tablets similar to the experimental drugs with the same regimen (one tablet /day for 24 weeks). Allocation concealment: will be ensured using sealed closed envelop randomization technique, every patient will be given an identification code.This research is a double-blinded , placebo-controlled, randomized clinical trial. Fifty patients with end-stage renal disease (ESRD) receiving hemodialysis treatment will be enrolled in the study.Patients will be randomly assigned using block randomization method into two study groups:Experimental group (25 patients): They will receive atorvastatin 10 mg, as one tablet /day for 24 weeks. Control group (25 patients): They will receive a placebo in the form of multivitamin tablets similar to the experimental drugs with the same regimen (one tablet /day for 24 weeks). Allocation concealment: will be ensured using sealed closed envelop randomization technique, every patient will be given an identification code.
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:
a double blinded study as participants, health care providers as well as the outcome assessor will be unaware about the type of treatment each patient receive.
Primary Purpose:
Treatment
Official Title:
Atorvastatin Effects On Arterial Stiffness In Hemodialysis Patients
Actual Study Start Date :
Nov 1, 2020
Actual Primary Completion Date :
May 1, 2021
Actual Study Completion Date :
Jul 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Atorvastatin

They will receive atorvastatin 10 mg, as one tablet /day for 24 weeks.

Drug: Atorvastatin
atorvastatin 10 mg, as one tablet /day for 24 weeks.
Other Names:
  • Lipitor, Ator

    		•
    Placebo Comparator: placebo

    They will receive a placebo in the form of multivitamin tablets similar to the experimental drug with the same regimen, as one tablet /day for 24 weeks.

    Drug: Placebo
    a placebo in the form of multivitamin tablets similar to the experimental drugs with the same regimen (one tablet /day for 24 weeks)

    Outcome Measures

    Primary Outcome Measures

    1. change in Aortic pulse wave velocity (PWV) [baseline, 24 weeks]

      the procedure was done at least 30 minutes after the dialysis session. Measurements were made after 10 minutes of rest in a supine position with a suitable cuff placed in the upper arm (the non-arteriovenous fistula arm in the hemodialysis group) and a connecting tube linking the cuff to a recorder device.Three consecutive measurements were taken automatically with 30 seconds of duration.

    2. change in Augmentation index (AIx) [baseline, 24 weeks]

      It is a surrogate index of arterial stiffness which measures pulse wave reflections that significantly influence the central pressure profile. It is directly related to peripheral arterial stiffness.

    Secondary Outcome Measures

    1. change in Central systolic blood pressure (CSP) [24 weeks]

      Central aortic systolic blood pressure is a parameter that strongly reflects vascular changes of central elastic arteries compared to peripheral brachial blood pressure

    2. change in Peripheral blood pressure (PBP) [baseline, 24 weeks]

      change in peripheral systolic and diastolic blood pressure

    3. change in central pulse pressure (PP) [baseline, 24 weeks]

      will be clalculated from the central waveform

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients on regular hemodialysis treatment for more than 3 months
    Exclusion Criteria:

    • Patients with diabetes mellitus.

    • Patients with known severe valvular heart disease.

    • Irregular heart rhythm.

    • History of aortic surgery/prosthetic aorta.

    • Acute liver disease.

    • Patients receiving lipid lowering drugs.

    • Pregnancy.

    • History of myocardial infraction in the previous 6 months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Faculty of Medicine, Aexandria University Alexandria Egypt 21526

    Sponsors and Collaborators

    • Alexandria University

    Investigators

    • Principal Investigator: Mohamed Mamdouh Elsayed, MD, lecturer
    • Study Chair: El Hassan M Ayman, MSc, Assistant lecturer

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD, Lecturer, Alexandria University
    ClinicalTrials.gov Identifier:
    NCT04472637
    Other Study ID Numbers:
    • arterial stiffness in HD
    First Posted:
    Jul 15, 2020
    Last Update Posted:
    Apr 15, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD, Lecturer, Alexandria University
    statin, hemodialysis
    Additional relevant MeSH terms:
    Atorvastatin

    Study Results

    No Results Posted as of Apr 15, 2022