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

Bicuspid Aortic Valve Clinical Trial

— BICATOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679261
• Other study ID #: BICATOR
• Status: Completed
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: February 2021

Study information

• Verified date: February 2021
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bicuspid Aortic Valve
• Heart Valve Diseases

Intervention

Drug:
• Atorvastatin
Oral administration atorvastatin 20 mg per day
• Placebo
Oral administration placebo

Locations

Country	Name	City	State
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitari Sant Joan de Reus	Reus	Tarragona
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Universitario de Vigo	Vigo	Pontevedra

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Antonini-Canterin F, Hîrsu 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. — View 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. — View 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. — View 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. — View Citation

Dichtl W, Alber HF, Feuchtner GM, Hintringer F, Reinthaler M, Bartel T, Süssenbacher A, Grander W, Ulmer H, Pachinger O, Müller 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. — View 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. — View 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. — View 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. — View Citation

Moura LM, Ramos SF, Zamorano JL, Barros IM, Azevedo LF, Rocha-Gonçalves 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. Epub 2007 Jan 22. — View Citation

Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi 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. — View Citation

Schouten O, van Laanen JH, Boersma E, Vidakovic R, Feringa HH, Dunkelgrün 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. Epub 2006 Mar 6. — View 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. — View 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. Epub 2005 Nov 21. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change of the transvalvular pressure gradient of the aortic valve	Difference of transvalvular pressure gradient of the aortic valve	3 years
Secondary	Change of aortic regurgitation jet width basal and final.	Difference of aortic regurgitation jet width basal and final.	3 years
Secondary	Change of the maximum aortic velocity	Change of the maximum aortic velocity	3 years
Secondary	Change of aortic valve area	Change of aortic valve area by continuity equation basal and final	3 years
Secondary	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