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

NCT02679261 | Completed Phase 3 DMC

• 1 other identifier: BICATOR
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 10

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.

Conditions

Bicuspid Aortic Valve

Keywords

Aortic dilation; Statins; Aortic degeneration

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change of 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.

  3 years

• Change of 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.

  3 years

• Change of the valve Agatston final score and the basal assessed by CT.

  3 years

Study Arms (2)

Atorvastatin

EXPERIMENTAL

Oral administration Atorvastatin 20 mg per day

Drug: Atorvastatin

Control

PLACEBO COMPARATOR

Oral administration of Placebo

Drug: Placebo

Interventions

Atorvastatin DRUG

Oral administration atorvastatin 20 mg per day

Atorvastatin

Placebo DRUG

Oral administration placebo

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (10)

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Vigo

Vigo, Pontevedra, 36200, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, Tarragona, 43204, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, 41071, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47005, Spain

Location

Related Publications (14)

• 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.

  PMID: 11181465 BACKGROUND

• 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.

  PMID: 16520071 BACKGROUND

• 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.

  PMID: 16442379 BACKGROUND

• 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.

  PMID: 21911808 BACKGROUND

• 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.

  PMID: 22221941 BACKGROUND

• 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.

  PMID: 24079445 BACKGROUND

• 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.

  PMID: 22040719 BACKGROUND

• 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.

  PMID: 15944423 BACKGROUND

• 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.

  PMID: 18774000 BACKGROUND

• 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.

  PMID: 17276178 BACKGROUND

• 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.

  PMID: 20048204 BACKGROUND

• 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.

  PMID: 18765433 BACKGROUND

• 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.

  PMID: 18773999 BACKGROUND

• Evangelista A, Galian-Gay L, Guala A, Teixido-Tura G, Calvo-Iglesias F, Sevilla T, Bermejo J, Mendez I, Sanchez V, Robledo Carmona JM, Alegret JM, Ferrer-Sistach E, Saura D, Ruiz-Munoz A, Dux-Santoy L, Carmona MA, Huguet M, Cuellar-Calabria H, Sao-Aviles A, Ferreira-Gonzalez I, Rodriguez-Palomares JF. Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial. Circulation. 2024 Jun 18;149(25):1938-1948. doi: 10.1161/CIRCULATIONAHA.123.067537. Epub 2024 May 28.

  PMID: 38804148 DERIVED

MeSH Terms

Conditions

Bicuspid Aortic Valve Disease

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Aortic Valve Disease; Heart Valve Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Arturo Evangelista-Masip, MD, PhD, Professor

  Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: February 10, 2016
• Study Start: June 1, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: February 18, 2021

Record last verified: 2021-02

Locations

ES (10)