Randomized Study to Evaluate the Efficacy of Fluvastatin on Inflammatory Markers in Patients With Aortic Stenosis.

Double Blind Randomized Phase IV Clinical Trial to Evaluate the Efficacy of Fluvastatin on Inflammatory Markers in the Haemodynamic Progression of Degenerative Aortic Stenosis. The AORTICA 1 Study.

Atherosclerosis and aortic stenosis share inflammatory etiopathogenic characteristics in common. We hypothesized that statins therapy would decrease inflammatory markers concentrations in patients with degenerative aortic stenosis and halt the haemodynamic progression of the disease.

Study Overview

• Status: Terminated
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Drug: Fluvastatin

Detailed Description

This study will be a prospective, phase IV-III, randomized, double blinded, active controlled study, to evaluate the efficacy of fluvastatin on inflammatory markers in the haemodynamic progression of degenerative aortic stenosis. We hypothesized that statins therapy would decrease inflammatory markers concentrations in patients with degenerative aortic stenosis and halt the haemodynamic progression of the disease. Eligible patients with degenerative aortic stenosis will be randomized 1:1 to fluvastatin 80 mg once daily or placebo. The treatment should be continued until the study end (12 months). Follow up investigations will be performed after 3 months and at the end of the study (12 months).

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Salamanca, Spain, 37002
    • Hospital Universitario de Salamanca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Asymptomatic
3. Aortic stenosis defined as aortic valve leaflet thickening with reduced systolic opening (maximum aortic jet velocity >2 m/s)
4. Written informed consent to participate in the study
5. Patients capable to follow all conditions along the study.

Exclusion Criteria:

1. Symptomatic patients caused by aortic stenosis.
2. Patients on statins anytime in the year before inclusion.
3. Patients diagnosed of dyslipidemia requiring statins.
4. Temperature ³37,8 ºC in the week before inclusion.
5. Any cardiovascular event succeeding in the three months before inclusion
6. Known thyrotoxicosis
7. Renal failure requiring hemodialysis
8. Any inflammatory noncardiac diseases or other reasons known to influence the study biomarkers concentrations.
9. Any surgery succeeding in the three months before inclusion.
10. Patients with any hepatopathy that in the view of the investigator prohibits participation in the study.
11. Patients with known muscular disease.
12. Patients with any severe medical condition that in the view of the investigator prohibits participation in the study
13. Use of corticoids, immunosuppressors or non steroid drugs.
14. Any known sensitivity to study drug (fluvastatin) or class of study drug.
15. Patients participating in any study in the last year.
16. Women of childbearing potential not using the contraception method(s) specified in this study, suspicion of pregnancy, as well as women who are breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Fluvastatin
Active Comparator: fluvastatin; fluvastatin 80 mg	Drug: Fluvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To study changes in CRP (mg/dL) concentration at the end of the study (12 months)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To study changes in other inflammatory biomarkers (specify in the protocol) at the end of the study (12 months)	12 months
To study changes in these biomarkers in the different grades of aortic stenosis at the end of the study (12 months)	12 months
To study changes change in aortic valve area and medium aortic transvalvular gradient at the end of the study (12 months)	12 months
To study the safety and tolerability of fluvastatin in patients with aortic stenosis.	12 months

Collaborators and Investigators

• Sponsor: AORTICA Group
• Investigators: Principal Investigator: Pedro L Sanchez, MD, PhD, Hospital Universitario Gregorio Marañón de Madrid; Study Chair: Candido Martin-Luengo, MD, PhD, University of Salamanca

Publications and helpful links

General Publications

• Sanchez PL, Mazzone A. C-reactive protein in degenerative aortic valve stenosis. Cardiovasc Ultrasound. 2006 Jun 14;4:24. doi: 10.1186/1476-7120-4-24.
• Sanchez PL, Santos JL, Kaski JC, Cruz I, Arribas A, Villacorta E, Cascon M, Palacios IF, Martin-Luengo C; Grupo AORTICA (Grupo de Estudio de la Estenosis Aortica). Relation of circulating C-reactive protein to progression of aortic valve stenosis. Am J Cardiol. 2006 Jan 1;97(1):90-3. doi: 10.1016/j.amjcard.2005.07.113. Epub 2005 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2006
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 27, 2006
• First Submitted That Met QC Criteria: November 27, 2006
• First Posted (Estimate): November 28, 2006

Study Record Updates

• Last Update Posted (Actual): June 7, 2019
• Last Update Submitted That Met QC Criteria: June 6, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Aortic valve stenosis; progression; C reactive protein
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: CXUO320BES04; EudraCT number 2005-003666-42

Plan for Individual participant data (IPD)

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