Aortic Valve StenosisPhase 4BETA-TAVINCT05721170
Impact of Beta Blockers on TAVI (BETA-TAVI)
A Phase 4 study testing Beta blocker in people with Aortic Valve Stenosis, run by National and Kapodistrian University of Athens at 2 sites in 2 countries.
Trial summary
The BETA-TAVI trial is a prospective, investigator-initiated, multicenter, randomized, open-label, non-inferiority trial designed to evaluate the safety of continuing versus temporarily interrupting chronic beta-blocker therapy in patients undergoing transcatheter aortic valve implantation (TAVI) for severe… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- Beta blocker
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Jun 2024to 31 Jan 2028
- Phase
- Phase 4
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
Study population
Eligibility Adults scheduled to undergo TAVI for severe symptomatic aortic stenosis are eligible when they are receiving chronic oral beta-blocker therapy and satisfy all inclusion criteria without meeting any exclusion criterion.
Inclusion criteria Age 18 years or older. Severe symptomatic aortic stenosis, defined by one or more of the following: mean transvalvular gradient >=40 mmHg, peak aortic-jet velocity >=4.0 m/s, aortic-valve area <=1.0 cm2, or indexed aorticvalve area <=0.6 cm2/m2. Clinical and anatomical suitability for TAVI confirmed by the local multidisciplinary Heart Team.
Current oral beta-blocker treatment for a recognized clinical indication. Ability and willingness to comply with the assigned treatment strategy and follow-up schedule.
Written informed consent before any trial-specific procedure.
Exclusion criteria Existing permanent pacemaker, implantable cardioverter-defibrillator or cardiac resynchronization device. Second-degree Mobitz II, advanced second-degree or third-degree atrioventricular block at screening, unless a permanent device is already clinically indicated independently of the trial.
Resting heart rate below 50 beats/min at the screening or baseline electrocardiogram.
A clinical condition requiring mandatory beta-blocker continuation or mandatory withdrawal such that randomization would be unsafe or inappropriate. Active infection, including active infective endocarditis. Left-atrial or left-ventricular thrombus on imaging. Contraindication to the antithrombotic regimen required for TAVI. Known hypersensitivity to required procedural drugs, contrast media or device components that cannot be adequately managed. Estimated life expectancy below 12 months because of non-cardiac disease. Pregnancy or potential for pregnancy without reliable contraception. Comorbidity or social circumstance expected to prevent reliable assessment of the 7-day primary endpoint or scheduled follow-up. Participation in another interventional study that is considered likely to interfere with the assigned treatment or endpoint assessment.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Cyprus1 site, 1 recruiting
- Recruiting
Nicosia General Hospital
Nicosia
Christos Eftychiou, MD, PhD, 35722604284, chr6eft@gmail.com
Greece1 site, 1 recruiting
- Recruiting
First Department of Cardiology, National and Kapodistrian University of Athens
Athens, Attica, 11527
Konstantinos Toutouzas, MD, PhD, 00302132088147, ktoutouz@gmail.com
About this study
Official title: Impact of Beta-blocker Continuation Versus Interruption in Patients Undergoing Transcatheter Aortic Valve Implantation
The BETA-TAVI trial is a prospective, investigator-initiated, multicenter, randomized, open-label, non-inferiority trial designed to evaluate the safety of continuing versus temporarily interrupting chronic beta-blocker therapy in patients undergoing transcatheter aortic valve implantation (TAVI) for severe symptomatic aortic stenosis.
A total of 348 patients receiving chronic oral beta-blocker therapy will be randomized in a 1:1 ratio to either continuation of their prescribed beta-blocker from at least 72 hours before TAVI through 7 days after the procedure or temporary interruption of beta-blocker therapy during the same period. Treatment modifications will be permitted when clinically indicated.
Read more
The primary objective is to determine whether beta-blocker continuation is non-inferior to interruption regarding the incidence of new permanent pacemaker implantation within 7 days after TAVI, using an absolute non-inferiority margin of 6.5 percentage points.
Secondary outcomes include atrioventricular conduction disturbances, atrial and ventricular arrhythmias, hemodynamic deterioration, subsequent permanent pacemaker implantation, and all-cause and cardiovascular mortality. Clinical follow-up will be performed at discharge, 7 days, 30 days, and 12 months after TAVI.
Read the detailed description
The BETA-TAVI trial is a prospective, investigator-initiated, multicenter, randomized, open-label, controlled non-inferiority trial designed to investigate the impact of periprocedural beta-blocker continuation versus temporary interruption on conduction disturbances and clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI).
Background and Rationale
New-onset conduction disturbances and the subsequent need for permanent pacemaker implantation remain important complications following TAVI. Beta-blockers are frequently prescribed in this population for various cardiovascular indications, including heart failure, atrial fibrillation, coronary artery disease, and ventricular arrhythmias. However, the optimal management of chronic beta-blocker therapy during the periprocedural period remains uncertain.
Continuation of beta-blocker therapy may theoretically exacerbate bradycardia and atrioventricular conduction disturbances, potentially increasing the need for permanent pacemaker implantation. Conversely, abrupt discontinuation may lead to sympathetic rebound, tachyarrhythmias, myocardial ischemia, and hemodynamic instability. Available observational studies have reported conflicting findings, and randomized evidence directly comparing these strategies is lacking.
The BETA-TAVI trial aims to address this evidence gap by evaluating whether continuation of chronic beta-blocker therapy is non-inferior to temporary interruption regarding the incidence of new permanent pacemaker implantation within 7 days following TAVI.
Study Design and Population
The study will enroll 348 adult patients (174 per treatment group) with severe symptomatic aortic stenosis who are scheduled to undergo TAVI and are receiving chronic oral beta-blocker therapy for an established clinical indication.
Eligible participants must be considered suitable for TAVI following multidisciplinary Heart Team assessment and provide written informed consent. Key exclusion criteria include pre-existing permanent pacemakers or other implantable cardiac rhythm devices, advanced atrioventricular block, resting heart rate below 50 beats/min, and clinical conditions requiring mandatory continuation or discontinuation of beta-blocker therapy.
Participants will be randomized in a 1:1 ratio using a centralized allocation procedure to one of two treatment strategies:
- Beta-blocker continuation: Participants will continue their prescribed beta-blocker, maintaining the same active substance and dose from at least 72 hours before TAVI through completion of the day-7 assessment. Dose modification or temporary withholding will be permitted when clinically indicated.
- Beta-blocker interruption: Participants will discontinue beta-blocker therapy 72 hours before TAVI and remain without beta-blocker treatment until completion of the day-7 assessment. Earlier reinitiation will be permitted when clinically necessary, including for uncontrolled tachyarrhythmias, myocardial ischemia, heart failure, or hemodynamic instability.
All TAVI procedures and subsequent clinical management will follow contemporary guideline-based practice and local institutional standards. The choice of transcatheter heart valve, procedural technique, and postprocedural rhythm monitoring will remain at the discretion of the treating Heart Team. Decisions regarding permanent pacemaker implantation will be made according to established clinical indications, independently of treatment allocation.
Study Objectives and Outcomes
The primary objective is to determine whether continuation of chronic beta-blocker therapy is non-inferior to temporary interruption with respect to the incidence of new permanent pacemaker implantation within 7 days (168 hours) following TAVI.
The primary endpoint is the occurrence of new permanent pacemaker implantation from the start of the TAVI procedure through 7 days after intervention.
Secondary endpoints include:
- New permanent pacemaker implantation beyond 7 days and through 30 days and 12 months.
- High-degree atrioventricular block and newly developed conduction disturbances, including bundle-branch block.
- New-onset atrial fibrillation or flutter and sustained ventricular arrhythmias.
- Clinically significant bradycardia.
- Hemodynamic deterioration requiring vasoactive or inotropic therapy or mechanical circulatory support.
- All-cause and cardiovascular mortality at 30 days and 12 months.
- Treatment adherence, dose modifications, premature beta-blocker reinitiation, and treatment crossover.
Exploratory outcomes include temporary pacing duration, time to permanent pacemaker implantation, hospital length of stay, changes in electrocardiographic conduction parameters, and heart failure hospitalization.
Clinical and electrocardiographic assessments will be performed at baseline, during hospitalization, at discharge, and at 7 days, 30 days, and 12 months following TAVI. The primary endpoint and other prespecified clinical events will undergo blinded adjudication whenever feasible.
Statistical Considerations
The study is designed to test non-inferiority using an absolute risk-difference margin of 6.5 percentage points for the 7-day permanent pacemaker implantation rate, comparing beta-blocker continuation with interruption.
The planned sample size of 348 participants provides approximately 80% statistical power at a one-sided significance level of 0.025, based on anticipated event rates of 7.2% and 9.5% in the continuation and interruption groups, respectively, while allowing for limited non-evaluability.
The primary analysis will compare the absolute difference in event rates between treatment groups using a Miettinen-Nurminen score-based 95% confidence interval. Non-inferiority will be established if the upper confidence limit is below the prespecified margin of 6.5 percentage points in both the modified intention-to-treat and per-protocol populations.
Prespecified secondary, sensitivity, and subgroup analyses will further evaluate the consistency of treatment effects across clinically relevant patient and procedural characteristics.
Clinical Significance
The BETA-TAVI trial is intended to provide randomized evidence regarding the optimal periprocedural management of chronic beta-blocker therapy in patients undergoing TAVI. By assessing the balance between conduction-related complications and potential arrhythmic or hemodynamic consequences of beta-blocker interruption, the findings may inform clinical practice and contribute to the development of standardized medication-management strategies in this population.
- Conditions
- Aortic Valve Stenosis
- Being tested
- Beta blocker
- Keywords
- TAVI, Aortic valve stenosis, TAVR, Pacemaker implantation, Beta blocker
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beta blockerDrug
Investigation on beta-blockers in TAVI and brief post-TAVI period.
| Study group | Role | What they receive |
|---|---|---|
| Beta-blockers continuation | Active comparator | Patients assigned in the beta-blockers continuation arm will be receiving per os beta blocker medication for at least 72 hours before TAVI without interruption after it. Receives: Drug: Beta blocker |
| Beta-blockers interruption | Active comparator | Patients assigned to interrupt the beta-blockers treatment will abstain from beta blockers for at least 7 days after TAVI. Receives: Drug: Beta blocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Permanent pacemaker implantation
Permanent pacemaker implantation
Measured: 7 days
Secondary outcomes (9)
All-cause mortality
All-cause mortality
Measured: 12 months
Cardiovascular mortality
Cardiovascular mortality
Measured: 12 months
Hemodynamic deterioration
Shock or circulatory instability requiring intravenous vasopressor or inotropic therapy, or mechanical circulatory support.
Measured: 12 months
Atrial fibrillation or flutter
New documented atrial fibrillation/flutter in a participant without that rhythm at baseline; recurrent clinically documented episodes will also be reported separately.
Measured: 12 months
Sustained ventricular arrhythmia
Sustained ventricular tachycardia or ventricular fibrillation requiring intervention or lasting at least 30 seconds.
Measured: 12 months
New conduction disturbance
New left bundle-branch block, right bundle-branch block, first-degree atrioventricular block or other clinically relevant intraventricular conduction delay.
Measured: 12 months
Severe bradycardia
Documented heart rate below 50 beats/min with symptoms, treatment or clinical concern; asymptomatic episodes will be described separately.
Measured: 12 months
High-degree atrioventricular block
Mobitz II second-degree, advanced second-degree or complete atrioventricular block.
Measured: 12 months
Permanent pacemaker implantation after day 7
New permanent pacemaker implantation not included in the primary endpoint. >7 days to 30 days; >30 days to 12 months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start1 Jun 2024
- Primary completion30 Jan 2028 (estimated)
- Study completion31 Jan 2028 (estimated)
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 Aortic Valve StenosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible patients will be assigned randomly in 1:1 ratio to either continue or withdraw the already receiving beta-blocker medication
- Masking
- None (open label)
- Enrolment
- 348 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Collaborators
- Evaggelismos Hospital, Greece, Interbalkan Medical Center, Thessaloniki, Greece
- Responsible party
- Principal investigator, Konstantinos Toutouzas, National and Kapodistrian University of Athens
- Investigators
- Leonidas Koliastasis, MD, MSc, Principal investigator, National and Kapodistrian University of AthensKonstantinos Toutouzas, Professor, Study director, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05721170
- Sponsor's protocol ID
- BETA-TAVI Trial
- Acronym
- BETA-TAVI
- Status last verified
- Oct 2026
- First submitted
- 28 Jan 2023
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Aurigemma G, Battista S, Orsinelli D, Sweeney A, Pape L, Cuenoud H. Abnormal left ventricular intracavitary flow acceleration in patients undergoing aortic valve replacement for aortic stenosis. A marker for high postoperative morbidity and mortality. Circulation. 1992 Sep;86(3):926-36. doi: 10.1161/01.cir.86.3.926.
PubMed 1516206Authors/Task Force members; Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014 Oct 14;35(39):2733-79. doi: 10.1093/eurheartj/ehu284. Epub 2014 Aug 29. No abstract available.
PubMed 25173338Brugada J, Katritsis DG, Arbelo E, Arribas F, Bax JJ, Blomstrom-Lundqvist C, Calkins H, Corrado D, Deftereos SG, Diller GP, Gomez-Doblas JJ, Gorenek B, Grace A, Ho SY, Kaski JC, Kuck KH, Lambiase PD, Sacher F, Sarquella-Brugada G, Suwalski P, Zaza A; ESC Scientific Document Group. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J. 2020 Feb 1;41(5):655-720. doi: 10.1093/eurheartj/ehz467. No abstract available.
PubMed 31504425Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available.
PubMed 34455430Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Feb 1;42(5):373-498. doi: 10.1093/eurheartj/ehaa612. No abstract available.
PubMed 32860505Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mahfoud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020 Jan 14;41(3):407-477. doi: 10.1093/eurheartj/ehz425. No abstract available.
PubMed 31504439Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, Doshi D, Cohen DJ, Pichard AD, Kapadia S, Dewey T, Babaliaros V, Szeto WY, Williams MR, Kereiakes D, Zajarias A, Greason KL, Whisenant BK, Hodson RW, Moses JW, Trento A, Brown DL, Fearon WF, Pibarot P, Hahn RT, Jaber WA, Anderson WN, Alu MC, Webb JG; PARTNER 2 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2016 Apr 28;374(17):1609-20. doi: 10.1056/NEJMoa1514616. Epub 2016 Apr 2.
PubMed 27040324Lioufas PA, Kelly DN, Brooks KS, Marasco SF. Unexpected suicide left ventricle post-surgical aortic valve replacement requiring veno-arterial extracorporeal membrane oxygenation support despite gold-standard therapy: a case report. Eur Heart J Case Rep. 2022 Feb 2;6(2):ytac020. doi: 10.1093/ehjcr/ytac020. eCollection 2022 Feb.
PubMed 35233483Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Pibarot P, Leipsic J, Hahn RT, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Pocock SJ, Alu MC, Webb JG, Smith CR; PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1695-1705. doi: 10.1056/NEJMoa1814052. Epub 2019 Mar 16.
PubMed 30883058Saito T, Yoshijima N, Hase H, Yashima F, Tsuruta H, Shimizu H, Fukuda K, Naganuma T, Mizutani K, Araki M, Tada N, Yamanaka F, Shirai S, Tabata M, Ueno H, Takagi K, Higashimori A, Watanabe Y, Yamamoto M, Hayashida K. Impact of beta blockers on patients undergoing transcatheter aortic valve replacement: the OCEAN-TAVI registry. Open Heart. 2020 Jul;7(2):e001269. doi: 10.1136/openhrt-2020-001269.
PubMed 32641381Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur J Cardiothorac Surg. 2021 Oct 22;60(4):727-800. doi: 10.1093/ejcts/ezab389. No abstract available.
PubMed 34453161Younis A, Orvin K, Nof E, Barabash IM, Segev A, Berkovitch A, Guetta V, Assali A, Kornowski R, Beinart R. The effect of periprocedural beta blocker withdrawal on arrhythmic risk following transcatheter aortic valve replacement. Catheter Cardiovasc Interv. 2019 Jun 1;93(7):1361-1366. doi: 10.1002/ccd.28017. Epub 2018 Nov 29.
PubMed 30489692Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, Charron P, Corrado D, Dagres N, de Chillou C, Eckardt L, Friede T, Haugaa KH, Hocini M, Lambiase PD, Marijon E, Merino JL, Peichl P, Priori SG, Reichlin T, Schulz-Menger J, Sticherling C, Tzeis S, Verstrael A, Volterrani M; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126. doi: 10.1093/eurheartj/ehac262. No abstract available.
PubMed 36017572Koliastasis L, Kim WK, Toutouzas K. Pacemaker Implantation After TAVR: Searching for the Golden Ratio. JACC Cardiovasc Interv. 2023 Aug 14;16(15):1946. doi: 10.1016/j.jcin.2023.06.002. No abstract available.
PubMed 37587606