search
Back to results

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

Primary Purpose

Bicuspid Aortic Valve

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Atorvastatin
Placebo
Sponsored by
Hospital Universitari Vall d'Hebron Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bicuspid Aortic Valve focused on measuring Aortic dilation, Statins, Aortic degeneration

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Universitari Germans Trias i Pujol
  • Hospital Universitario de Vigo
  • Hospital Universitari Sant Joan de Reus
  • Hospital Vall d'Hebron
  • Hospital General Universitario Gregorio Marañón
  • Hospital Universitario 12 de Octubre
  • Hospital Clínico Universitario Virgen de la Arrixaca
  • Hospital Universitario Virgen de la Victoria
  • Hospital Universitario Virgen de la Macarena
  • Hospital Clínico Universitario de Valladolid

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Atorvastatin

Control

Arm Description

Oral administration Atorvastatin 20 mg per day

Oral administration of Placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Change of the transvalvular pressure gradient of the aortic valve
Difference of transvalvular pressure gradient of the aortic valve
Change of aortic regurgitation jet width basal and final.
Difference of aortic regurgitation jet width basal and final.
Change of the maximum aortic velocity
Change of the maximum aortic velocity
Change of aortic valve area
Change of aortic valve area by continuity equation basal and final
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.

Full Information

First Posted
January 19, 2016
Last Updated
February 17, 2021
Sponsor
Hospital Universitari Vall d'Hebron Research Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT02679261
Brief Title
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve
Acronym
BICATOR
Official Title
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve (BICATOR)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
June 2016 (Actual)
Primary Completion Date
February 2021 (Actual)
Study Completion Date
February 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitari Vall d'Hebron Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bicuspid Aortic Valve
Keywords
Aortic dilation, Statins, Aortic degeneration

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atorvastatin
Arm Type
Experimental
Arm Description
Oral administration Atorvastatin 20 mg per day
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Oral administration of Placebo
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Intervention Description
Oral administration atorvastatin 20 mg per day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration placebo
Primary Outcome Measure Information:
Title
Change of the diameter of ascending aorta by CT (Computed Tomography).
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Change of the final maximum diameter of the aortic root and the basal measured by CT.
Description
Difference between the final maximum diameter of the aortic root and the basal measured by CT.
Time Frame
3 years
Title
Change of the final maximum diameter of the tubular ascending aorta and the basal measured by CT.
Description
Difference between the final maximum diameter of the tubular ascending aorta and the basal measured by CT.
Time Frame
3 years
Title
Change of the final area of the aortic root and the basal measured by CT.
Description
Difference between the final area of the aortic root and the basal measured by CT.
Time Frame
3 years
Title
Change of the the final area of ascending aorta and the basal measured by CT.
Description
Difference between the final area of ascending aorta and the basal measured by CT.
Time Frame
3 years
Title
Change of the valve Agatston final score and the basal assessed by CT.
Description
Difference between the valve Agatston final score and the basal assessed by CT.
Time Frame
3 years
Title
Change of the final planimetry area of the aortic valve and the basal measured by CT.
Description
Difference between the final planimetry area of the aortic valve and the basal measured by CT.
Time Frame
3 years
Title
Change of the transvalvular pressure gradient of the aortic valve
Description
Difference of transvalvular pressure gradient of the aortic valve
Time Frame
3 years
Title
Change of aortic regurgitation jet width basal and final.
Description
Difference of aortic regurgitation jet width basal and final.
Time Frame
3 years
Title
Change of the maximum aortic velocity
Description
Change of the maximum aortic velocity
Time Frame
3 years
Title
Change of aortic valve area
Description
Change of aortic valve area by continuity equation basal and final
Time Frame
3 years
Title
Ocurrence of Serious Adverse Clinical Events leading to hospitalization and death
Description
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.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arturo Evangelista-Masip, MD, PhD, Professor
Organizational Affiliation
Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Universitario de Vigo
City
Vigo
State/Province
Pontevedra
ZIP/Postal Code
36200
Country
Spain
Facility Name
Hospital Universitari Sant Joan de Reus
City
Reus
State/Province
Tarragona
ZIP/Postal Code
43204
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Clínico Universitario Virgen de la Arrixaca
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario Virgen de la Macarena
City
Sevilla
ZIP/Postal Code
41071
Country
Spain
Facility Name
Hospital Clínico Universitario de Valladolid
City
Valladolid
ZIP/Postal Code
47005
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
11181465
Citation
Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001 Feb 20;103(7):926-33. doi: 10.1161/01.cir.103.7.926.
Results Reference
background
PubMed Identifier
16520071
Citation
Schouten O, van Laanen JH, Boersma E, Vidakovic R, Feringa HH, Dunkelgrun M, Bax JJ, Koning J, van Urk H, Poldermans D. Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth. Eur J Vasc Endovasc Surg. 2006 Jul;32(1):21-6. doi: 10.1016/j.ejvs.2005.12.024. Epub 2006 Mar 6.
Results Reference
background
PubMed Identifier
16442379
Citation
Sukhija R, Aronow WS, Sandhu R, Kakar P, Babu S. Mortality and size of abdominal aortic aneurysm at long-term follow-up of patients not treated surgically and treated with and without statins. Am J Cardiol. 2006 Jan 15;97(2):279-80. doi: 10.1016/j.amjcard.2005.08.033. Epub 2005 Nov 21.
Results Reference
background
PubMed Identifier
21911808
Citation
McLoughlin D, McGuinness J, Byrne J, Terzo E, Huuskonen V, McAllister H, Black A, Kearney S, Kay E, Hill AD, Dietz HC, Redmond JM. Pravastatin reduces Marfan aortic dilation. Circulation. 2011 Sep 13;124(11 Suppl):S168-73. doi: 10.1161/CIRCULATIONAHA.110.012187.
Results Reference
background
PubMed Identifier
22221941
Citation
Jovin IS, Duggal M, Ebisu K, Paek H, Oprea AD, Tranquilli M, Rizzo J, Memet R, Feldman M, Dziura J, Brandt CA, Elefteriades JA. Comparison of the effect on long-term outcomes in patients with thoracic aortic aneurysms of taking versus not taking a statin drug. Am J Cardiol. 2012 Apr 1;109(7):1050-4. doi: 10.1016/j.amjcard.2011.11.038. Epub 2012 Jan 3.
Results Reference
background
PubMed Identifier
24079445
Citation
Stein LH, Berger J, Tranquilli M, Elefteraides JA. Effect of statin drugs on thoracic aortic aneurysms. Am J Cardiol. 2013 Oct 15;112(8):1240-5. doi: 10.1016/j.amjcard.2013.05.081.
Results Reference
background
PubMed Identifier
22040719
Citation
Goel SS, Tuzcu EM, Agarwal S, Aksoy O, Krishnaswamy A, Griffin BP, Svensson LG, Kapadia SR. Comparison of ascending aortic size in patients with severe bicuspid aortic valve stenosis treated with versus without a statin drug. Am J Cardiol. 2011 Nov 15;108(10):1458-62. doi: 10.1016/j.amjcard.2011.06.071.
Results Reference
background
PubMed Identifier
15944423
Citation
Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, Northridge DB, Boon NA; Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) Investigators. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005 Jun 9;352(23):2389-97. doi: 10.1056/NEJMoa043876.
Results Reference
background
PubMed Identifier
18774000
Citation
Dichtl W, Alber HF, Feuchtner GM, Hintringer F, Reinthaler M, Bartel T, Sussenbacher A, Grander W, Ulmer H, Pachinger O, Muller S. Prognosis and risk factors in patients with asymptomatic aortic stenosis and their modulation by atorvastatin (20 mg). Am J Cardiol. 2008 Sep 15;102(6):743-8. doi: 10.1016/j.amjcard.2008.04.060. Epub 2008 Jul 2.
Results Reference
background
PubMed Identifier
17276178
Citation
Moura LM, Ramos SF, Zamorano JL, Barros IM, Azevedo LF, Rocha-Goncalves F, Rajamannan NM. Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis. J Am Coll Cardiol. 2007 Feb 6;49(5):554-61. doi: 10.1016/j.jacc.2006.07.072. Epub 2007 Jan 22.
Results Reference
background
PubMed Identifier
20048204
Citation
Chan KL, Teo K, Dumesnil JG, Ni A, Tam J; ASTRONOMER Investigators. Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation. 2010 Jan 19;121(2):306-14. doi: 10.1161/CIRCULATIONAHA.109.900027. Epub 2010 Jan 4.
Results Reference
background
PubMed Identifier
18765433
Citation
Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56. doi: 10.1056/NEJMoa0804602. Epub 2008 Sep 2.
Results Reference
background
PubMed Identifier
18773999
Citation
Antonini-Canterin F, Hirsu M, Popescu BA, Leiballi E, Piazza R, Pavan D, Ginghina C, Nicolosi GL. Stage-related effect of statin treatment on the progression of aortic valve sclerosis and stenosis. Am J Cardiol. 2008 Sep 15;102(6):738-42. doi: 10.1016/j.amjcard.2008.04.056. Epub 2008 Jun 26.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs