Aortic Valve StenosisDANAVRNCT03972644
Danish National Randomized Study on Early Aortic Valve Replacement in Patients With Asymptomatic Severe Aortic Stenosis
A study testing Aortic valve replacement in people with Aortic Valve Stenosis and Diastolic Dysfunction, run by Odense University Hospital at 1 site in Denmark.
Trial summary
The purpose of this study is to examine the impact of early surgery in patients with asymptomatic severe aortic valve stenosis with signs of subclinical LV dysfunction despite preserved LVEF, with a watchfull waiting approach. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Aortic Valve Stenosis, Diastolic Dysfunction
- What is being tested?
- Aortic valve replacement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,700 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jan 2020to 1 Sep 2029
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Severe AS defined as
- aortic valve area (AVA) ≤1 cm2, AND
- Transvalvular maximum velocity (Vmax) ≥3.5 m/s AND
- AS severity evaluated severe by a heart valve team conference. In cases where severity is not unambiguous an integrative approach will be utilized combining echocardiographic markers of valve severity and LV function, and if necessary aortic valve calcification estimated by non-contrast CT.
- 2. Considered to be asymptomatic (estimated by a consultant in cardiology) 3. Considered to be candidate for AVR (transcatheter AVR/surgical AVR) 4. Sign of increased LV filling pressures18 or reduced longitudinal LV systolic function
- <!-- -->
Show all 10Show fewer
- Left atrial volume index (LAVi) > 34 ml/m2; OR
- ratio of early diastolic peak mitral inflow velocity (E) to early mitral annulus diastolic velocity (e') ratio E/e'avg>13; OR
- Threefold elevation in NT-proBNP compared to the upper expected age and gender value. OR
- GLS>-15 5. Age ≥18 years 6. Signed informed consent
Who cannot join
- LVEF<50%
- Very severe AS defined as Vmax>5 m/s.
- Concomitant severe valvular disease other than AS
- Previous valvular surgery
- Estimated glomerular filtration rate<30 ml/min/m2
- Dementia
Show all 10Show fewer
- Women of childbearing potential
- Inability to provide informed consent
- Age>85 years.
- Supravalvular or subvalvular AS
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jacob E Møller, MD, PhD contact
Denmark1 site, 1 recruiting
- Recruiting
Odense University Hospital
Odense, Fyn, 5000
Jordi S Dahl, MD, Ph.D, 23823016, jordi.dahl@rsyd.dk
About this study
The purpose of this study is to examine the impact of early surgery in patients with asymptomatic severe aortic valve stenosis with signs of subclinical LV dysfunction despite preserved LVEF, with a watchfull waiting approach.
Read the detailed description
Since the seminal paper by Ross and Braunwald, the development of symptoms has been regarded as one of the most important precursors of a poor outcome in aortic stenosis (AS), and is today half a century later, still the leading reason for referral for aortic valve replacement (AVR). The development of symptoms is however often preceded by structural changes in the left ventricle (LV).These changes including concentric remodeling and LV hypertrophy have been regarded as compensative measures to adapt the LV to increased ventricular afterload. Although LV hypertrophy may preserve wall-stress in the normal range and increase contractility allowing the preservation of stroke volume, this occurs at the expense of increased filling pressures. Diastolic dysfunction with increased filling pressure lead to left atrial (LA) dilatation and significantly contributes to the development of symptoms.
Despite successful surgery, AS patients have increased long-term mortality and morbidity compared to the general population, and the outcome is largely determined by the degree of preoperative structural LV and LA alterations. This has led to the theory that AVR prior to the development of symptoms could improve outcome, a view supported by prospective and retrospective studies.These studies were however small, with some important limitations. In addition, there has been a concern that operative risk and prosthetic valve related long-term morbidity and mortality does not justify surgery on every asymptomatic patient with severe AS. Numerous studies have suggested that markers of LV structure and function, particularly LA volume index,E/e' and brain natriuretic peptides (BNP) all reflecting LV filling pressures may identify patients with benefit of early AVR. Accordingly, the most recent European guideline for management of valvular disease has implemented BNP as a class IIa recommendation for AVR in asymptomatic AS patients,although no randomized studies have demonstrated that early surgery based on these markers improve prognosis.
The purpose of this study is thus to evaluate if early AVR in patients with signs of elevated LV filling pressuresmay improve long-term outcome in patients with asymptomatic severe AS, compared to conventional symptom-guided surgery.
- Conditions
- Aortic Valve Stenosis, Diastolic Dysfunction
- Being tested
- Aortic valve replacement
- 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.
Aortic valve replacementProcedure or surgery
Open heart surgery or transcatheter surgery
| Study group | Role | What they receive |
|---|---|---|
| Early intervention | Active comparator | Patients will undergo aortic valve replacement immediately Receives: Procedure: Aortic valve replacement |
| Watchfull waiting | No intervention | Patients will be followed and treated as recommended by guidelines. |
What is being measured
The primary outcome is the main question the study is designed to answer.
all-cause mortality
All-cause mortality assessed by Danish patient records
Measured: After 379 events (approx 5 years)
Secondary outcomes (3)
Combined endpoint
All-cause mortality + hospitalization due to heart failure and stroke
Measured: After 379 events (approx 5 years)
all-cause mortality in patients with low-gradient AS
All-cause mortality in patients with meangradient <40 mmHg
Measured: After 379 events (approx 5 years)
Combined endpoint in low-gradient AS
All-cause mortality + hospitalization to heart failure and stroke when MG<40 mmHg
Measured: After 379 events (approx 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2019
- Study start1 Jan 2020
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Aarhus University Hospital, Aalborg University Hospital, Zealand University Hospital
- Responsible party
- Principal investigator, Jordi Dahl, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03972644
- Sponsor's protocol ID
- S-20190006
- Acronym
- DANAVR
- Status last verified
- Sep 2020
- First submitted
- 31 May 2019
- Last updated
- 14 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Danish National Randomized Study on Early Aortic Valve Replacement in Patients With Asymptomatic Severe Aortic Stenosis
- ClinicalTrials.gov ID
- NCT03972644
- Acronym / sponsor ID
- DANAVR / S-20190006
- Conditions
- Aortic Valve Stenosis, Diastolic Dysfunction
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,700 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Aarhus University Hospital, Aalborg University Hospital, Zealand University Hospital
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 1 Sep 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 3 Jun 2019 (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 purpose of this study is to examine the impact of early surgery in patients with asymptomatic severe aortic valve stenosis with signs of subclinical LV dysfunction despite preserved LVEF, with a watchfull waiting approach.
Detailed description
Since the seminal paper by Ross and Braunwald, the development of symptoms has been regarded as one of the most important precursors of a poor outcome in aortic stenosis (AS), and is today half a century later, still the leading reason for referral for aortic valve replacement (AVR). The development of symptoms is however often preceded by structural changes in the left ventricle (LV).These changes including concentric remodeling and LV hypertrophy have been regarded as compensative measures to adapt the LV to increased ventricular afterload. Although LV hypertrophy may preserve wall-stress in the normal range and increase contractility allowing the preservation of stroke volume, this occurs at the expense of increased filling pressures. Diastolic dysfunction with increased filling pressure lead to left atrial (LA) dilatation and significantly contributes to the development of symptoms.
Despite successful surgery, AS patients have increased long-term mortality and morbidity compared to the general population, and the outcome is largely determined by the degree of preoperative structural LV and LA alterations. This has led to the theory that AVR prior to the development of symptoms could improve outcome, a view supported by prospective and retrospective studies.These studies were however small, with some important limitations. In addition, there has been a concern that operative risk and prosthetic valve related long-term morbidity and mortality does not justify surgery on every asymptomatic patient with severe AS. Numerous studies have suggested that markers of LV structure and function, particularly LA volume index,E/e' and brain natriuretic peptides (BNP) all reflecting LV filling pressures may identify patients with benefit of early AVR. Accordingly, the most recent European guideline for management of valvular disease has implemented BNP as a class IIa recommendation for AVR in asymptomatic AS patients,although no randomized studies have demonstrated that early surgery based on these markers improve prognosis.
The purpose of this study is thus to evaluate if early AVR in patients with signs of elevated LV filling pressuresmay improve long-term outcome in patients with asymptomatic severe AS, compared to conventional symptom-guided surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early intervention | Active comparator | Procedure: Aortic valve replacementPatients will undergo aortic valve replacement immediately |
| Watchfull waiting | No intervention | –Patients will be followed and treated as recommended by guidelines. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 1. Severe AS defined as
- 2. Considered to be asymptomatic (estimated by a consultant in cardiology) 3. Considered to be candidate for AVR (transcatheter AVR/surgical AVR) 4. Sign of increased LV filling pressures18 or reduced longitudinal LV systolic function
- <!-- -->
Key exclusion criteria (10 listed)
- LVEF<50%
- Very severe AS defined as Vmax>5 m/s.
- Concomitant severe valvular disease other than AS
- Previous valvular surgery
- Estimated glomerular filtration rate<30 ml/min/m2
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 |
|---|---|---|
| Aortic valve replacementOpen heart surgery or transcatheter surgery | Procedure or surgery | Early intervention |
Primary outcome
all-cause mortality
Time frame: After 379 events (approx 5 years)
All-cause mortality assessed by Danish patient records
3 secondary outcomes
Combined endpoint
Time frame: After 379 events (approx 5 years)
all-cause mortality in patients with low-gradient AS
Time frame: After 379 events (approx 5 years)
Combined endpoint in low-gradient AS
Time frame: After 379 events (approx 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 14 Sep 2020.
- Individual participant dataSharing planned: No
Related trials for Aortic Valve Stenosis
Recruiting
SYMmetric Valve fraME Expansion To Reduce hYpoattenuated Leaflet Thickening After Balloon-expandable TAVI: the SYMMETRY Trial
Aortic Valve Stenosis and/or Insufficiency, Hypoattenuated Leaflet Thickening
RecruitingObservational study
Spanish Prospective Registry of Hydra THV for Transcatheter Aortic Valve Implantation
Severe Aortic Valve Stenosis, Valvular Heart Disease
RecruitingObservational study
Korea VHD Echo Study: Surveillance of Aortic, Mitral & Tricuspid Patients - Insights From Real-world Practice
Heart Valve Diseases, Aortic Valve Stenosis
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
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.
Jacob E Møller, MD, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aortic valve replacement in people with Aortic Valve Stenosis and Diastolic Dysfunction, run by Odense University Hospital at 1 site in Denmark.
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 10 inclusion and 10 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 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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 Jordi S Dahl, MD, PhD (+4523823016, jordi.dahl@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
all-cause mortality (time frame: After 379 events (approx 5 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2020.