Aortic Valve StenosisPhase 3DIRECTNCT02448927
The preDIlatation in tRanscathEter aortiC Valve implanTation Trial
A Phase 3 study testing balloon aortic valvuloplasty and Transcatheter Aortic Valve Implantation in people with Aortic Valve Stenosis, run by National and Kapodistrian University of Athens at 4 sites in 2 countries.
Trial summary
This is a randomized trial that will evaluate the role of balloon aortic valvuloplasty (BAV) on the outcome of patients undergoing transcatheter aortic valve implantation (TAVI) procedure. Patients will undergo a physical exam, coronary angiography and computed tomography angiography before TAVI. 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?
- balloon aortic valvuloplasty and Transcatheter Aortic Valve Implantation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 4 sitesin 2 countries
- Study dates
- May 2015to 2 May 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Diameter of >5mm for Evolut R and >6mm for CoreValve of the vessel.
- Aortic valve diameter of ≥20mm and ≤29mm as measured by echo.
- Ascending aorta diameter ≤ 43mm at the sinotubular junction.
- Severe aortic stenosis, defined as aortic valve area of < 1.0 cm2 (or aortic valve area index of < 0.6 cm2/m2) by the continuity equation, AND mean gradient > 40 mmHg or maximal aortic valve velocity > 4.0 m/sec by resting echocardiogram.
- STS score of ≥ 8 OR LogEuroSCORE> 20%, OR
- 80 years old OR
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- 65 years old with 1 or 2 (but not more than two) from the following criteria:
- Liver cirrhosis (Class A or B).
- Pulmonary insufficiency: VMS<1 liter.
- Previous heart surgery (CABG, vascular surgery).
- Porcelain aorta.
- Pulmonary artery systolic pressure >60 mmHg and high risk for heart surgery.
- Relapsing pulmonary embolism.
- Right ventricular insufficiency.
- Thoracic wall injuries that contraindicate an open heart surgery.
- History of radiation therapy of the mediastinum.
- Connective tissue disease that contraindicates an open heart surgery.
- Frailty/cachexia.
- Patients will be informed on the nature of the study and provide written consent.
Who cannot join
- A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated: aspirin or heparin and bivalirudin, ticlopidine and clopidogrel, nitinol (titanium or nickel), contrast media
- Ongoing sepsis, including active endocarditis.
- Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to Heart Team assessment.
- Echocardiographic evidence of LV or LA thrombus.
- Mitral or tricuspid valve insufficiency (> grade II).
- Previous aortic valve replacement (mechanical or bioprosthetic).
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- Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
- Patients with:
- Femoral, iliac or aortic vascular disease (stenosis etc) that precludes the insertion of a transcatheter sheath.
- OR Symptomatic carotid or vertebral artery disease (> 70% stenosis).
- The patient has a bleeding diathesis, coagulopathy or denies blood transfusion.
- Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions.
- Creatinine clearance < 20 ml/min.
- Active gastritis or ulcer.
- Pregnancy.
- Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20%.
- Unicuspid or bicuspid aortic valve.
- Mixed aortic valve disease (aortic stenosis and aortic regurgitation> 2+).
- Liver failure (Child-Pugh class C).
- Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
- Extreme aortic valve calcification and calcific asymmetry (if semiquantitively measured: grade 4, Agatston score: grade 4 AgS>5000 AU).
- Aortic valve area of < 0.4 cm2.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Greece3 sites
First Department of Cardiology, University of Athens
Athens, Attica, 11527
Department of Cardiology, Onassis Cardiac Surgery Center
Athens
Second Department of Cardiology, University Hospital of Ioannina
Ioannina
Israel1 site
Heart Institute Hadassah Hebrew University Medical Center
Jerusalem, 91120
About this study
This is a randomized trial that will evaluate the role of balloon aortic valvuloplasty (BAV) on the outcome of patients undergoing transcatheter aortic valve implantation (TAVI) procedure. Patients will undergo a physical exam, coronary angiography and computed tomography angiography before TAVI. The randomization for direct or non-direct TAVI ( with BAV or without BAV) will take place 24 hours prior to the procedure by the core lab at Hippokration Hospital in Athens. The same lab will analyze in blind fashion the results of all the imaging modalities for each patient. The patients will be followed during the hospital stay and at 30 days and 1 year thereafter by echocardiography. The procedure of predilatation will be at the operator's discretion.
Read the detailed description
Background: Balloon aortic valvuloplasty (BAV) is a vital part of the transcatheter aortic valve implantation (TAVI) procedure. There is a lack of long-term evidence in patients undergoing direct TAVI without predilatation.
Trial: This is a prospective multi-center randomized trial.
Participating medical centers:
- 1st Department of Cardiology, Hippokration Hospital/Athens Medical School, Athens, Greece
- Heart Institute, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel.
- Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška 7, SI-1525 Ljubljana, Slovenia.
- Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
- Second Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece
Description: Patients will undergo a physical exam, coronary angiography and computed tomography angiography before TAVI. The randomization for direct or non-direct TAVI will take place 24 hours prior to the procedure by the core lab at Hippokration Hospital in Athens. The same lab will analyze in blind fashion the results of all the imaging modalities for each patient. The patients will be followed during the hospital stay and at 30 days and 1 year thereafter by echocardiography. The procedure of predilatation will be at the operator's discretion. Access sites for TAVI are: transfemoral, subclavian and transaortic.
- Conditions
- Aortic Valve Stenosis
- Being tested
- balloon aortic valvuloplasty, Transcatheter Aortic Valve Implantation
- Keywords
- transcatheter aortic valve implantation, Balloon aortic valvuloplasty, Aortic stenosis, TAVI, TAVR (transcatheter aortic valve replacement), CoreValve, BAV, Evolut R
- 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.
balloon aortic valvuloplastyDevice
Also called BAV
Transcatheter Aortic Valve ImplantationDevice
Also called TAVI
| Study group | Role | What they receive |
|---|---|---|
| TAVI patients without balloon aortic valvuloplasty | Other | Patients that will not undergo balloon aortic valvuloplasty (BAV) before transcatheter aortic valve intervention (TAVI) with the Medtronic Evolut R (or CoreValve). Receives: Device: Transcatheter Aortic Valve Implantation |
| TAVI patients with balloon aortic valvuloplasty | Active comparator | Patients that will undergo balloon aortic valvuloplasty (BAV) before transcatheter aortic valve intervention (TAVI) with the Medtronic Evolut R (or CoreValve). Receives: Device: balloon aortic valvuloplasty; Device: Transcatheter Aortic Valve Implantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Device success
Device success, as designated by the VARC-2 criteria.
Measured: 30 days
Secondary outcomes (5)
Death
Death during the hospitalization of the patient, as designated by the VARC-2 criteria.
Measured: 30 days
Cerebrovascular accident
Cerebrovascular accident during and after the hospitalization of the patient, as designated by the VARC-2 criteria.
Measured: 30 days and 1 year
New pacemaker implantation
New pacemaker implantation during the hospitalization of the patient, as designated by the VARC-2 criteria.
Measured: 30 days
Vascular complications
Vascular complications during the hospitalization of the patient, as designated by the VARC-2 criteria.
Measured: 30 days
Mortality
Death after discharge of the patient, as designated by the VARC-2 criteria.
Measured: after 30 days and at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2015 (estimated)
- Study startMay 2015
- Primary completion2 May 2018
- Study completion2 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
- More trials run by National and Kapodistrian University of AthensThe sponsor's other registered studies.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- National and Kapodistrian University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Konstantinos Toutouzas, University of Athens
- Investigators
- Dimitrios Tousoulis, Professor, Study chair, University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02448927
- Sponsor's protocol ID
- DIRECT Trial
- Acronym
- DIRECT
- Status last verified
- Sep 2019
- First submitted
- 14 Jan 2015
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Toutouzas K, Benetos G, Voudris V, Drakopoulou M, Stathogiannis K, Latsios G, Synetos A, Antonopoulos A, Kosmas E, Iakovou I, Katsimagklis G, Mastrokostopoulos A, Moraitis S, Zeniou V, Danenberg H, Vavuranakis M, Tousoulis D. Pre-Dilatation Versus No Pre-Dilatation for Implantation of a Self-Expanding Valve in All Comers Undergoing TAVR: The DIRECT Trial. JACC Cardiovasc Interv. 2019 Apr 22;12(8):767-777. doi: 10.1016/j.jcin.2019.02.005. Epub 2019 Mar 27.
PubMed 30928442
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The preDIlatation in tRanscathEter aortiC Valve implanTation Trial
- ClinicalTrials.gov ID
- NCT02448927
- Acronym / sponsor ID
- DIRECT / DIRECT Trial
- Conditions
- Aortic Valve Stenosis
- Keywords
- transcatheter aortic valve implantation, Balloon aortic valvuloplasty, Aortic stenosis, TAVI, TAVR (transcatheter aortic valve replacement), CoreValve, BAV, Evolut R
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- National and Kapodistrian University of AthensUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- 2 May 2018 (actual)
- Study completion
- 2 May 2018 (actual)
- First posted
- 20 May 2015 (estimated)
- 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.
This is a randomized trial that will evaluate the role of balloon aortic valvuloplasty (BAV) on the outcome of patients undergoing transcatheter aortic valve implantation (TAVI) procedure. Patients will undergo a physical exam, coronary angiography and computed tomography angiography before TAVI. The randomization for direct or non-direct TAVI ( with BAV or without BAV) will take place 24 hours prior to the procedure by the core lab at Hippokration Hospital in Athens. The same lab will analyze in blind fashion the results of all the imaging modalities for each patient. The patients will be followed during the hospital stay and at 30 days and 1 year thereafter by echocardiography. The procedure of predilatation will be at the operator's discretion.
Detailed description
Background: Balloon aortic valvuloplasty (BAV) is a vital part of the transcatheter aortic valve implantation (TAVI) procedure. There is a lack of long-term evidence in patients undergoing direct TAVI without predilatation.
Trial: This is a prospective multi-center randomized trial.
Participating medical centers:
- 1st Department of Cardiology, Hippokration Hospital/Athens Medical School, Athens, Greece
- Heart Institute, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel.
- Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška 7, SI-1525 Ljubljana, Slovenia.
- Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece
- Second Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece
Description: Patients will undergo a physical exam, coronary angiography and computed tomography angiography before TAVI. The randomization for direct or non-direct TAVI will take place 24 hours prior to the procedure by the core lab at Hippokration Hospital in Athens. The same lab will analyze in blind fashion the results of all the imaging modalities for each patient. The patients will be followed during the hospital stay and at 30 days and 1 year thereafter by echocardiography. The procedure of predilatation will be at the operator's discretion. Access sites for TAVI are: transfemoral, subclavian and transaortic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAVI patients without balloon aortic valvuloplasty | Other | Device: Transcatheter Aortic Valve ImplantationPatients that will not undergo balloon aortic valvuloplasty (BAV) before transcatheter aortic valve intervention (TAVI) with the Medtronic Evolut R (or CoreValve). |
| TAVI patients with balloon aortic valvuloplasty | Active comparator | Device: balloon aortic valvuloplasty, Device: Transcatheter Aortic Valve ImplantationPatients that will undergo balloon aortic valvuloplasty (BAV) before transcatheter aortic valve intervention (TAVI) with the Medtronic Evolut R (or CoreValve). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Diameter of >5mm for Evolut R and >6mm for CoreValve of the vessel.
- Aortic valve diameter of ≥20mm and ≤29mm as measured by echo.
- Ascending aorta diameter ≤ 43mm at the sinotubular junction.
- Severe aortic stenosis, defined as aortic valve area of < 1.0 cm2 (or aortic valve area index of < 0.6 cm2/m2) by the continuity equation, AND mean gradient > 40 mmHg or maximal aortic valve velocity > 4.0 m/sec by resting echocardiogram.
- STS score of ≥ 8 OR LogEuroSCORE> 20%, OR
Key exclusion criteria (22 listed)
- A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated: aspirin or heparin and bivalirudin, ticlopidine and clopidogrel, nitinol (titanium or nickel), contrast media
- Ongoing sepsis, including active endocarditis.
- Any percutaneous coronary or peripheral interventional procedure with a bare metal or drug eluting stent performed within 30 days prior to Heart Team assessment.
- Echocardiographic evidence of LV or LA thrombus.
- Mitral or tricuspid valve insufficiency (> grade II).
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 |
|---|---|---|
| balloon aortic valvuloplastyAlso: BAV | Device | TAVI patients with balloon aortic valvuloplasty |
| Transcatheter Aortic Valve ImplantationAlso: TAVI | Device | TAVI patients with balloon aortic valvuloplasty, TAVI patients without balloon aortic valvuloplasty |
Primary outcome
Device success
Time frame: 30 days
Device success, as designated by the VARC-2 criteria.
5 secondary outcomes
Death
Time frame: 30 days
Cerebrovascular accident
Time frame: 30 days and 1 year
New pacemaker implantation
Time frame: 30 days
Vascular complications
Time frame: 30 days
Mortality
Time frame: after 30 days and at 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Derived from this study: PubMed 30928442Toutouzas K, Benetos G, Voudris V, Drakopoulou M, Stathogiannis K, Latsios G, Synetos A, Antonopoulos A, Kosmas E, Iakovou I, Katsimagklis G, Mastrokostopoulos A, Moraitis S, Zeniou V, Danenberg H, Vavuranakis M, Tousoulis D. Pre-Dilatation Versus No Pre-Dilatation for Implantation of a Self-Expanding Valve in All Comers Undergoing TAVR: The DIRECT Trial. JACC Cardiovasc Interv. 2019 Apr 22;12(8):767-777. doi: 10.1016/j.jcin.2019.02.005. Epub 2019 Mar 27.
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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. This study is not recruiting at the moment.
Dimitrios Tousoulis, Professor study chair
University of Athens
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing balloon aortic valvuloplasty and Transcatheter Aortic Valve Implantation in people with Aortic Valve Stenosis, run by National and Kapodistrian University of Athens at 4 sites in 2 countries.
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 19 inclusion and 22 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: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Greece, Israel. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device success (time frame: 30 days). 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 NCT02448927, which also lists 1 linked publication.
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 6 Sep 2019.