RecruitingNCT05310461TIAMARUpdated Nov 21, 2023

Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis and Mitral Regurgitation

An interventional study of 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 Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation, sponsored by Insel Gruppe AG, University Hospital Bern. Recruiting at 3 sites in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-11-21.

Sponsored by Insel Gruppe AG, University Hospital Bern · Not applicable, Interventional, and Treatment

From the registry’s dates

Primary completion was expected by Jul 2024, 2 years 3 months ago, but the record still lists the study as recruiting.
Started Aug 2022; still recruiting 4 years 2 months later.

Phase: Not applicable
Study type: Interventional
Enrollment: 80
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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 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).

Conditions studied

Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation

In context

Lead sponsor

Insel Gruppe AG, University Hospital Bern is the lead sponsor of 737 studies on the registry; 178 are open to participants now.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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
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.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 80 participants (estimated)

Study arms

Experimental
Early transcatheter or surgical aortic valve replacement
Early transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.
Procedure: Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement
Other
Control Intervention
Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention.
Procedure: Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention

Interventions

ProcedureTranscatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement
Early transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.
ProcedureDeferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention
Deferred transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.

What researchers measure

Primary outcomes

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

Secondary outcomes

All-cause death
Number of all-cause death within study participation
Time frame: 5 years
Cardiovascular death
Number of patients with Cardiovascular death within study participation
Time frame: 5 years
Neurologic events
Number of patients with stroke, symptomatic hypoxic-ischaemic injury, TIA and evaluation
Time frame: 5 years
Hospitalization for heart failure
Number of patients who need hospitalization for heart failure within study participation and evaluation
Time frame: 5 years
New-onset atrial fibrillation
Number of patients with new-onset atrial fibrillation within study participation and evaluation
Time frame: 5 years
Implantation of a permanent pacemaker
Number of patients with atrioventricular conductance disturbance requiring the implantation of a permanent pacemaker
Time frame: 5 years
Aortic or mitral valve re-intervention
Number of patients with Aortic or mitral valve re-intervention within study participation and evaluation
Time frame: 5 years
NYHA functional class
Measurement of NYHA functional class within study participation
Time frame: 5 years
Days alive out of hospital (DAOH)
Calculation of days alive out of hospital (DAOH) within study participation
Time frame: 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
Time frame: 5 years

Other outcomes

Major vascular complications (VARC-3)
Number of patients with major vascular complications within the study population and evaluation
Time frame: 5 years
Cardiac structural complications (major, minor) (VARC-3)
Number of patients with cardiac structural complications within the study population and evaluation
Time frame: 5 years
Cerebrovascular events (disabling and non-disabling stroke, and TIA) (VARC-3)
Number of patients with Cerebrovascular events (disabling and non-disabling stroke, and TIA) (VARC-3) within the study population and evaluation
Time frame: 5 years
Myocardial infarction
Number of patients with Myocardial infarction within the study population and evaluation
Time frame: 5 years
Acute kidney injury (VARC-3)
Number of patients with acute kidney injury (VARC-3) within the study population and evaluation
Time frame: 5 years
Access-related non-vascular major complications (VARC-3)
Number of patients with access-related non-vascular major complications (VARC-3) within the study population and evaluation
Time frame: 5 years
Bleeding type 3-5 (VARC-3)
Record all bleeding type 3-5 (VARC-3) within the study population
Time frame: 5 years
Prosthetic valve endocarditis
Number of patients Prosthetic valve endocarditis within the study population
Time frame: 5 years
Prosthetic valve thrombosis
Number of patients prosthetic valve thrombosis within the study population
Time frame: 5 years
Valve-related dysfunction requiring reintervention
Number of patients valve-related dysfunction requiring reintervention within the study population
Time frame: 5 years

Study locations

3 of 3 sites recruiting

Insel Gruppe AG, Inselspital Bern
Bern, 3010, Switzerland
- Thomas Pilgrim, Prof · Contact
Recruiting
University Hospital Geneva (HUG)
Geneva, Switzerland
- Stephane Noble, Prof · Contact
Recruiting
Heart Clinic Hirslanden
Zurich, Switzerland
- Peter Wenaweser, Prof · Contact
Recruiting

References and documents

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 27590452 ↗
Khan 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 32646692 ↗
Unger 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 ↗

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Started Aug 2022 (actual). Primary completion is estimated for Jul 2024, 22 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered: Mar 25, 2022
First posted: Apr 5, 2022
StartActual: Aug 17, 2022
Primary completionEst.: Jul 1, 2024
CompletionEst.: Jan 1, 2030
Last update: Nov 21, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Nov 21, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05310461
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Responsible party: Sponsor
First posted: Apr 5, 2022
Start date: Aug 17, 2022
Primary completion: Jul 1, 2024 (estimated)
Completion: Jan 1, 2030 (estimated)
Last update: Nov 21, 2023

Study contacts

Thomas Pilgrim, Prof. Dr.

Contact

kardio.studien@insel.ch

0041316325000

Bartowiak Joanna, Dr. med.

Contact

kardio.studien@insel.ch

0041316325000

Thomas Pilgrim, Prof. Dr.

principal investigator · Insel Gruppe AG

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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