Bicuspid Aortic ValvePhase 3BICATORNCT02679261
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve
A Phase 3 study testing Atorvastatin in people with Bicuspid Aortic Valve, run by Hospital Universitari Vall d'Hebron Research Institute at 10 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bicuspid Aortic Valve
- What is being tested?
- Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 10 sitesSpain
- Study dates
- Jun 2016to Feb 2021
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Vall d'Hebron
Barcelona, 08035
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, 30120
Hospital Universitari Sant Joan de Reus
Reus, Tarragona, 43204
Hospital Universitario Virgen de la Macarena
Seville, 41071
Hospital Clínico Universitario de Valladolid
Valladolid, 47005
Hospital Universitario de Vigo
Vigo, Pontevedra, 36200
About this study
Official title: Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve (BICATOR)
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.
Read the 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).
- Conditions
- Bicuspid Aortic Valve
- Being tested
- Atorvastatin, Placebo
- Keywords
- Aortic dilation, Statins, Aortic degeneration
- Medical subject headings
- Bicuspid Aortic Valve Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Oral administration atorvastatin 20 mg per day
PlaceboDrug
Oral administration placebo
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Experimental | Oral administration Atorvastatin 20 mg per day Receives: Drug: Atorvastatin |
| Control | Placebo comparator | Oral administration of Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (11)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3 years
Change of the transvalvular pressure gradient of the aortic valve
Difference of transvalvular pressure gradient of the aortic valve
Measured: 3 years
Change of aortic regurgitation jet width basal and final.
Difference of aortic regurgitation jet width basal and final.
Measured: 3 years
Change of the maximum aortic velocity
Change of the maximum aortic velocity
Measured: 3 years
Change of aortic valve area
Change of aortic valve area by continuity equation basal and final
Measured: 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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study startJun 2016
- Primary completionFeb 2021
- Study completionFeb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Bicuspid Aortic ValveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Arturo Evangelista-Masip, MD, PhD, Professor, Principal investigator, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679261
- Sponsor's protocol ID
- BICATOR
- Acronym
- BICATOR
- Status last verified
- Feb 2021
- First submitted
- 19 Jan 2016
- Last updated
- 18 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 11181465Schouten 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.
PubMed 16520071Sukhija 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.
PubMed 16442379McLoughlin 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.
PubMed 21911808Jovin 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.
PubMed 22221941Stein 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.
PubMed 24079445Goel 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.
PubMed 22040719Cowell 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.
PubMed 15944423Dichtl 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.
PubMed 18774000Moura 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.
PubMed 17276178Chan 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.
PubMed 20048204Rossebo 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.
PubMed 18765433Antonini-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.
PubMed 18773999Evangelista 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.
PubMed 38804148