Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve

Study Overview
=================
Brief Summary
-----------------
Bicuspid Aortic Valve (BAV) is the most common congenital heart disease affecting 1-2% of the population. The aortic dilation and aortic valve degeneration are common complications in patients with BAV. Statins have shown a reduction in the expression of metalloproteinases of the extracellular matrix observed in aortic aneurisms. Several retrospective studies have suggested the benefit of the statins to reduce aortic dilation in patients with BAV. Moreover, although statins did not show to be useful in the progression of aortic stenosis, different studies have suggested a higher profit when the valve affection is not severe. The objective of this study is to determine whether atorvastatin is effective at reducing the progression of aortic dilation in patients with BAV.

Detailed Description
-----------------
BICATOR is a multicentre (8 centres), randomised, double-blind and placebo-controlled clinical trial aimed at evaluating the effect of atorvastatin in reducing progression of aortic dilation in patients with BAV. The primary outcome is to determine whether atorvastatin is effective in reducing aortic dilation in BAV and secondary outcome is to define if atorvastatin treatment slows the progression of aortic valve degeneration (valve calcification) in a 3 year follow-up period. 220 patients will be included (110 atorvastatin - 110 placebo).

Official Title
-----------------
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve (BICATOR)

Conditions
-----------------
Bicuspid Aortic Valve

Intervention / Treatment
-----------------
* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥ 18 years old with BAV confirmed by transthoracic echocardiography (in case of doubts other techniques will be required: transesophageal echocardiography or CT to confirm diagnosis). Valve dysfunction only moderate: in case of aortic stenosis with average gradient < 30 mmHg and in case of aortic regurgitation a vena contracta < 7 mm or a jet with < 10 mm. Aortic valve not show severe calcification by transthoracic echocardiography. Ascending aortic diameter (Valsalva sinus or tubular ascending aorta) ≤ 50 mm. The patient must give the consent form signed. Exclusion Criteria: Patients younger than 18. Patients with uncontrolled hypertension and a history or risk of diabetes mellitus. Patients who receive statins treatment or other lipid lowering drug or if they have indication to be treated according to the current clinical practice guidelines. Previous cardiac surgery or any surgery of other segments of the aorta. Previous aortic dissection and/or aortic coarctation. NYHA functional class III or IV. Presence or antecedent of liver failure (transaminase > 2 fold the superior limit of normal levels according to local laboratory), renal failure (creatinine clearance < 30ml/min or creatinine > 2.5mg/dl), myopathy or creatine kinase levels > 5 fold the superior limit of normality, or other gastrointestinal, hematologic or endocrine diseases or any other situation that according to the investigator criteria could affect the study treatment evaluation. Hypersensitivity, intolerance or contraindication to any component of the study drug or to the contrast used in CT. Pregnancy, breastfeeding or desire for pregnancy during the study period. A negative pregnancy test (negative gonadotropin) will be required in all fertile women to participate in the study. Participation in another drug study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>Oral administration Atorvastatin 20 mg per day | Drug: Atorvastatin<br>* Oral administration atorvastatin 20 mg per day<br>|
| Placebo Comparator: Control<br>Oral administration of Placebo | Drug: Placebo<br>* Oral administration placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the diameter of ascending aorta by CT (Computed Tomography). | Determination of the progression of ascending aortic dilation assessed by measuring the change of the diameter of ascending aorta by CT (Computed Tomography).The change of the aortic diameter will be defined by the major difference between the measurements taken in the aortic root and ascending aorta in the initial and final study. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the final maximum diameter of the aortic root and the basal measured by CT. | Difference between the final maximum diameter of the aortic root and the basal measured by CT. | 3 years | 
| Change of the final maximum diameter of the tubular ascending aorta and the basal measured by CT. | Difference between the final maximum diameter of the tubular ascending aorta and the basal measured by CT. | 3 years | 
| Change of the final area of the aortic root and the basal measured by CT. | Difference between the final area of the aortic root and the basal measured by CT. | 3 years | 
| Change of the the final area of ascending aorta and the basal measured by CT. | Difference between the final area of ascending aorta and the basal measured by CT. | 3 years | 
| Change of the valve Agatston final score and the basal assessed by CT. | Difference between the valve Agatston final score and the basal assessed by CT. | 3 years | 
| Change of the final planimetry area of the aortic valve and the basal measured by CT. | Difference between the final planimetry area of the aortic valve and the basal measured by CT. | 3 years | 
| Change of the transvalvular pressure gradient of the aortic valve | Difference of transvalvular pressure gradient of the aortic valve | 3 years | 
| Change of aortic regurgitation jet width basal and final. | Difference of aortic regurgitation jet width basal and final. | 3 years | 
| Change of the maximum aortic velocity | Change of the maximum aortic velocity | 3 years | 
| Change of aortic valve area | Change of aortic valve area by continuity equation basal and final | 3 years | 
| Ocurrence of Serious Adverse Clinical Events leading to hospitalization and death | Serious Adverse Clinical Events: Aortic dissection, aortic rupture or need for aortic surgery, cardiovascular death, death of any cause. Combined endpoint of death, aortic dissection or need for aortic or valve surgery. | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aortic dilation, Statins, Aortic degeneration