Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral RegurgitationTIAMARNCT05310461
Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis and Mitral Regurgitation
A study testing Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement and Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention in people with Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation, run by Insel Gruppe AG, University Hospital Bern at 3 sites in Switzerland.
Trial summary
The aim of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with moderate mitral regurgitation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation
- What is being tested?
- Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement and Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 3 sitesSwitzerland
- Study dates
- 17 Aug 2022to 1 Jan 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Age ≥18 years
- Moderate native aortic stenosis defined by an aortic valve area (AVA) ≤1.5 cm2 and >1.0 cm2 and transvalvular mean gradient ≥20 mmHg and <40 mmHg.
- Primary or secondary mitral regurgitation (at least moderate) defined by effective regurgitant orifice area (EROA) ≥20 mm2 or regurgitant volume ≥30 ml
- New York Heart Association (NYHA) functional class ≥2
Who cannot join
- Life expectancy <1 year irrespective of valvular heart disease
- Left ventricular ejection fraction <30% or LVESD >70mm
- Echocardiographic evidence of severe right ventricular dysfunction
- Untreated clinically significant CAD requiring revascularisation
- Moderate or severe aortic regurgitation
- Severe tricuspid valve disease requiring intervention
Show all 14Show fewer
- Symptomatic patients with severe primary MR who are operable and not high risk
- Patients with severe secondary MR who remain symptomatic despite optimal medical therapy and who are judged appropriate for transcatheter edge-to-edge repair or surgery by the Heart Team
- Transcatheter or surgical treatment of valvular and/or coronary artery disease within 90 days prior to randomization
- COPD with home oxygen therapy
- Estimated or measured systolic PAP >70 mmHg
- Stroke within 30 days prior to the randomization
- Inability to provide written informed consent
- Participation in another cardiovascular trial before reaching the primary endpoint.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland3 sites, 3 recruiting
- Recruiting
Insel Gruppe AG, Inselspital Bern
Bern, 3010
Thomas Pilgrim, Prof
- Recruiting
University Hospital Geneva (HUG)
Geneva
Stephane Noble, Prof
- Recruiting
Heart Clinic Hirslanden
Zurich
Peter Wenaweser, Prof
About this study
Official title: Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation: a Randomized Clinical Trial
The aim of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with moderate mitral regurgitation.
Read the detailed description
In more than one-half of all patients with valvular heart disease, more than a single valve is involved. Valvular aortic stenosis coexists with significant mitral valve disease in up to one-third of patients undergoing aortic valve replacement (AVR).
Guidelines for the management of valvular heart disease provide recommendations for isolated valvular lesions; data to guide timing of intervention in patients with multivalvular disease is however scarce. Currently, patients with moderate aortic stenosis (AS) in combination with mitral regurgitation have an indication for aortic valve replacement (AVR) only if the concomitant mitral regurgitation meets an indication for surgery. However, the hemodynamic stress of combined valvular lesions is greater than its individual components, and patients may benefit from early intervention.
Furthermore, the presence of multivalvular heart disease complicates the assessment of individual valvular lesions. In patients with combined AS and mitral regurgitation (MR), increased left ventricular pressure exacerbates the mitral regurgitant volume. Conversely, decreased forward flow across the aortic valve underestimates the severity of aortic stenosis when assessed by a pressure gradient.
Standard cut-off values inadequately reflect the hemodynamic stress in concomitant aortic and mitral valve disease, and recommendations for the timing of valvular replacement fail to account for the complex interplay of multiple valvular lesions.
Timing of intervention in patients with combined AS and MR is therefore challenging and evidence on the optimal timing of intervention is scarce.
Thus, the objective of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with at least moderate mitral regurgitation.
Patients with combined aortic stenosis and mitral regurgitation will be screened for eligibility. If eligible and informed consent is provided, patients will be randomly allocated in a 1:1 ratio to early (within 3 months) or deferred aortic valve replacement (with or without mitral valve intervention).
- Being tested
- Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement, Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacementProcedure or surgery
Early transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.
Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for interventionProcedure or surgery
Deferred transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.
| Study group | Role | What they receive |
|---|---|---|
| Early transcatheter or surgical aortic valve replacement | Experimental | Early transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement. Receives: Procedure: Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement |
| Control Intervention | Other | Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention. Receives: Procedure: Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be a composite of all-cause death, stroke, and unplanned hospitalization for heart failure related to valvular heart disease at 2 years.
Measured: 2 years
Secondary outcomes (10)
All-cause death
Number of all-cause death within study participation
Measured: 5 years
Cardiovascular death
Number of patients with Cardiovascular death within study participation
Measured: 5 years
Neurologic events
Number of patients with stroke, symptomatic hypoxic-ischaemic injury, TIA and evaluation
Measured: 5 years
Hospitalization for heart failure
Number of patients who need hospitalization for heart failure within study participation and evaluation
Measured: 5 years
New-onset atrial fibrillation
Number of patients with new-onset atrial fibrillation within study participation and evaluation
Measured: 5 years
Implantation of a permanent pacemaker
Number of patients with atrioventricular conductance disturbance requiring the implantation of a permanent pacemaker
Measured: 5 years
Aortic or mitral valve re-intervention
Number of patients with Aortic or mitral valve re-intervention within study participation and evaluation
Measured: 5 years
NYHA functional class
Measurement of NYHA functional class within study participation
Measured: 5 years
Days alive out of hospital (DAOH)
Calculation of days alive out of hospital (DAOH) within study participation
Measured: 5 years
The evaluation Health-related quality of life assessment by means of the KCCQ 12 questionnaire
Record the health-related quality of life assessment by means of the KCCQ 12 questionnaire within study participation
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study start17 Aug 2022
- Primary completion1 Jul 2024 (estimated)
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral RegurgitationStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Pilgrim, Prof. Dr., Principal investigator, Insel Gruppe AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05310461
- Sponsor's protocol ID
- TIAMAR
- Acronym
- TIAMAR
- Status last verified
- Nov 2023
- First submitted
- 25 Mar 2022
- Last updated
- 21 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shah AM, Solomon SD. Valvular heart disease in older adults: seeking an ounce of prevention. Eur Heart J. 2016 Dec 14;37(47):3523-3524. doi: 10.1093/eurheartj/ehw354. Epub 2016 Sep 1. No abstract available.
PubMed 27590452Khan F, Okuno T, Malebranche D, Lanz J, Praz F, Stortecky S, Windecker S, Pilgrim T. Transcatheter Aortic Valve Replacement in Patients With Multivalvular Heart Disease. JACC Cardiovasc Interv. 2020 Jul 13;13(13):1503-1514. doi: 10.1016/j.jcin.2020.03.052.
PubMed 32646692Unger P, Pibarot P, Tribouilloy C, Lancellotti P, Maisano F, Iung B, Pierard L; European Society of Cardiology Council on Valvular Heart Disease. Multiple and Mixed Valvular Heart Diseases. Circ Cardiovasc Imaging. 2018 Aug;11(8):e007862. doi: 10.1161/CIRCIMAGING.118.007862. No abstract available.
PubMed 30354497
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05310461
- Acronym / sponsor ID
- TIAMAR / TIAMAR
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 17 Aug 2022 (actual)
- Primary completion
- 1 Jul 2024 (estimated)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 5 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with moderate mitral regurgitation.
Detailed description
In more than one-half of all patients with valvular heart disease, more than a single valve is involved. Valvular aortic stenosis coexists with significant mitral valve disease in up to one-third of patients undergoing aortic valve replacement (AVR).
Guidelines for the management of valvular heart disease provide recommendations for isolated valvular lesions; data to guide timing of intervention in patients with multivalvular disease is however scarce. Currently, patients with moderate aortic stenosis (AS) in combination with mitral regurgitation have an indication for aortic valve replacement (AVR) only if the concomitant mitral regurgitation meets an indication for surgery. However, the hemodynamic stress of combined valvular lesions is greater than its individual components, and patients may benefit from early intervention.
Furthermore, the presence of multivalvular heart disease complicates the assessment of individual valvular lesions. In patients with combined AS and mitral regurgitation (MR), increased left ventricular pressure exacerbates the mitral regurgitant volume. Conversely, decreased forward flow across the aortic valve underestimates the severity of aortic stenosis when assessed by a pressure gradient.
Standard cut-off values inadequately reflect the hemodynamic stress in concomitant aortic and mitral valve disease, and recommendations for the timing of valvular replacement fail to account for the complex interplay of multiple valvular lesions.
Timing of intervention in patients with combined AS and MR is therefore challenging and evidence on the optimal timing of intervention is scarce.
Thus, the objective of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with at least moderate mitral regurgitation.
Patients with combined aortic stenosis and mitral regurgitation will be screened for eligibility. If eligible and informed consent is provided, patients will be randomly allocated in a 1:1 ratio to early (within 3 months) or deferred aortic valve replacement (with or without mitral valve intervention).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early transcatheter or surgical aortic valve replacement | Experimental | Procedure: Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacementEarly transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement. |
| Control Intervention | Other | Procedure: Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for interventionDeferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years
- Moderate native aortic stenosis defined by an aortic valve area (AVA) ≤1.5 cm2 and >1.0 cm2 and transvalvular mean gradient ≥20 mmHg and <40 mmHg.
- Primary or secondary mitral regurgitation (at least moderate) defined by effective regurgitant orifice area (EROA) ≥20 mm2 or regurgitant volume ≥30 ml
- New York Heart Association (NYHA) functional class ≥2
Key exclusion criteria (14 listed)
- Life expectancy <1 year irrespective of valvular heart disease
- Left ventricular ejection fraction <30% or LVESD >70mm
- Echocardiographic evidence of severe right ventricular dysfunction
- Untreated clinically significant CAD requiring revascularisation
- Moderate or severe aortic regurgitation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacementEarly transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement. | Procedure or surgery | Early transcatheter or surgical aortic valve replacement |
| Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for interventionDeferred transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement. | Procedure or surgery | Control Intervention |
Primary outcome
The primary outcome will be a composite of all-cause death, stroke, and unplanned hospitalization for heart failure related to valvular heart disease at 2 years.
Time frame: 2 years
10 secondary outcomes
All-cause death
Time frame: 5 years
Cardiovascular death
Time frame: 5 years
Neurologic events
Time frame: 5 years
Hospitalization for heart failure
Time frame: 5 years
New-onset atrial fibrillation
Time frame: 5 years
Implantation of a permanent pacemaker
Time frame: 5 years
Aortic or mitral valve re-intervention
Time frame: 5 years
NYHA functional class
Time frame: 5 years
Days alive out of hospital (DAOH)
Time frame: 5 years
The evaluation Health-related quality of life assessment by means of the KCCQ 12 questionnaire
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2023.
- Background: PubMed 27590452Shah AM, Solomon SD. Valvular heart disease in older adults: seeking an ounce of prevention. Eur Heart J. 2016 Dec 14;37(47):3523-3524. doi: 10.1093/eurheartj/ehw354. Epub 2016 Sep 1. No abstract available.
- Background: PubMed 32646692Khan F, Okuno T, Malebranche D, Lanz J, Praz F, Stortecky S, Windecker S, Pilgrim T. Transcatheter Aortic Valve Replacement in Patients With Multivalvular Heart Disease. JACC Cardiovasc Interv. 2020 Jul 13;13(13):1503-1514. doi: 10.1016/j.jcin.2020.03.052.
- Background: PubMed 30354497Unger P, Pibarot P, Tribouilloy C, Lancellotti P, Maisano F, Iung B, Pierard L; European Society of Cardiology Council on Valvular Heart Disease. Multiple and Mixed Valvular Heart Diseases. Circ Cardiovasc Imaging. 2018 Aug;11(8):e007862. doi: 10.1161/CIRCIMAGING.118.007862. No abstract available.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thomas Pilgrim, Prof. Dr. principal investigator
Insel Gruppe AG
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement and Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention in people with Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation, run by Insel Gruppe AG, University Hospital Bern at 3 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thomas Pilgrim, Prof. Dr. (0041316325000, kardio.studien@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome will be a composite of all-cause death, stroke, and unplanned hospitalization for heart failure related to valvular heart disease at 2 years. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05310461, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2023.