Clinical trial NCT05873816: The PROTEMBO Trial
Official title: Cerebral Protection in Transcatheter Aortic Valve Replacement: the PROTEMBO Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Severe Aortic Valve Stenosis
Keywords: TAVR
Cerebral embolic protection
Lead sponsor: Protembis GmbH
Sponsor class: INDUSTRY
First posted: 2023-05-24
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this prospective, multi-center, randomized, controlled study is to compare the safety and efficacy of the ProtEmbo Cerebral Embolic Protection device to a hybrid control (no embolic protection device ('No Device') and the Sentinel device) in subjects with severe symptomatic native aortic valve stenosis indicated undergoing a TAVR procedure.

Detailed description: Subjects with severe symptomatic aortic stenosis undergoing TAVR will be able to participate. Participants will be randomized in a 2:1:1 fashion to either the ProtEmbo arm, the Sentinel arm, or the 'No device' arm.

Enrolled subjects will undergo an MRI at baseline and at 36 hours ±12 hours, to evaluate any new cerebral lesions. Enrolled subjects will be followed for 30 days.

The study aims to address:

* whether the occurrence of all Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 days is comparable between the ProtEmbo group and the hybrid control group.
* whether the total new lesion volume in the brain assessed by diffusion weighted magnetic resonance images at 36 ±12 hours is comparable between the ProtEmbo group and the hybrid control group.

Eligibility criteria: Inclusion Criteria:

1. The heart team recommends transcatheter aortic valve replacement via femoral access consistent with the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease.
2. The subject and the treating physician agree that the subject will undergo the scheduled pre procedural testing and return for all required post procedure follow up visits.
3. The subject is able to provide informed consent, has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the relevant regulatory authority of the respective clinical site.
4. Subject is a minimum of 18 years of age.

Exclusion Criteria:

General exclusion criteria:

1. Subject is a woman of child-bearing potential.
2. Arm anatomy/ vasculature precluding radial or brachial artery access.
3. Hemodialysis shunt, graft, or arterio-venous fistula involving the upper extremity vasculature.
4. Evidence of an acute myocardial infarction ≤ 1 month before the intended treatment.
5. Severe ventricular dysfunction with LVEF ≤25%.
6. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 10 days of the index procedure.
7. Blood dyscrasias as defined by clinically significant leukopenia (\< 500 leukocytes / μL), acute anemia (Hgb \< 8 g / dL), thrombocytopenia (\< 80,000 platelets / μl), history of bleeding diathesis or coagulopathy.
8. Hemodynamic instability, or pressure dependence requiring pharmacological inotropic support or mechanical heart assistance.
9. Echocardiographic evidence of intracardiac or aortic mass, thrombus not adequately treated, or vegetation.
10. Active peptic ulcer or upper GI bleeding within the prior 6 months.
11. Contraindication for anticoagulant or antiplatelet therapy.
12. Renal insufficiency (creatinine \> 3.0 mg / dL or GFR \< 30) and / or renal replacement therapy at the time of screening and dialysis patients.
13. Current or planned treatment with any investigational drug or investigational device during the study follow-up period (30 days).
14. Balloon aortic valvuloplasty (BAV) within 30 days of the procedure.
15. Cardiogenic shock, hemodynamic instability, or severe hypotension (systolic blood pressure \< 90 mm Hg) at the time of the index procedure.
16. Cardiovascular surgical or interventional procedure 10 days prior or planned during the TAVR procedure or during the 30-day study follow-up.
17. Patients with severe chronic obstructive pulmonary disease (COPD)

NOTE: Use of general anesthesia during TAVR may affect neurocognitive function shortly after the procedure. While not an exclusion criterion, it is recommended that general anesthesia not be used if possible.

Neurological exclusion criteria:

1. Cerebrovascular event including TIA within 6 months of the procedure.
2. Subject had active major psychiatric disease.
3. Subject has severe visual, auditory, or learning impairment and is unable to comprehend English or local language and therefore unable to be consented for the study.
4. Subjects with neurodegenerative or other progressive neurological disease or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.

Magnetic resonance imaging exclusion criteria:

1. Body Mass Index (BMI) precluding imaging in scanner.
2. Contraindications to MRI (subjects with any implantable temporary or permanent pacemaker or defibrillator, metal implants in field of view, metallic fragments, clips, or devices in the brain or eye before TAVR procedure).
3. High risk of complete AV block after TAVR, with the need of permanent pacemaker (e.g., subjects with pre-existing bifascicular block or complete right bundle branch block plus any degree of AV block).
4. Planned implantation of a pacemaker or defibrillator implantation within the first 3 days after TAVR.
5. Claustrophobia precluding MRI scanning.

Anatomical and CT exclusion criteria:

1. Excessive tortuosity in left subclavian artery (≥ 70° single kink or ≥ 50° in sequential kinks).
2. Excessive tortuosity in right vascular access vessels for Sentinel introduction.
3. Significant stenosis (≥ 70%), calcification, ectasia, dissection, occlusion, aneurysm, or severe peripheral arterial disease in left or right arm access vessels - in particular at or within 3 cm of the aortic ostia.
4. Left subclavian artery diameter is ≤ 4 mm.
5. Brachiocephalic artery at the site of Sentinel filter placement \< 9 mm or \> 15 mm.
6. Left common artery at the site of Sentinel filter placement \< 6.5 mm or \> 10 mm.
7. Symptomatic or asymptomatic severe (≥ 70%) occlusive carotid disease requiring concomitant CEA / stenting.
8. Inner diameter of aortic arch \< 25 mm as measured in any position between ascending aorta and ostium of left subclavian artery.
9. Distance between the origin of left subclavian artery and valve plain of \< 90 mm.
10. Common ostium of cerebral vessels, where all three vessels originate from one single ostium in the aortic arch.
11. Significant stenosis, ectasia, dissection, aneurysm, or atheroma (mobile or \> 5 mm thick) in the ascending aorta or in the aortic arch.
12. Significant angulation of the proximal segment of the left subclavian or aortic arch angulation or abnormal anatomical conditions of the aorta (a Type 3 aortic arch is not a reason for exclusion).
13. Distance between the origin of brachiocephalic trunk and left subclavian artery of \> 65 mm.

Primary outcomes:
measure: MACCE at 30 days
timeFrame: Up to Day 30 post procedure
measure: Total new lesion volume
timeFrame: 36 ±12 hours post TAVR procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Clearwater
country: United States
facility: BayCare Health System / Morton Plant Hospital
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke&#39;s Hospital of Kansas City
state: Missouri
city: St Louis
country: United States
facility: Washington University - St. Louis
state: Missouri
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: New York City
country: United States
facility: NYU Langone
state: New York
city: New York City
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center / NYPH
state: New York
city: New York
country: United States
facility: Weill Medical College / Cornell University
state: New York
city: Houston
country: United States
facility: University of Texas, Memorial Hermann Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia, Charlottesville
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Dresden
country: Germany
facility: Dresden Herzzentrum
city: Lübeck
country: Germany
facility: Lübeck Universitätsklinikum Schleswig-Holstein Campus
city: Trier
country: Germany
facility: Trier Krankenhaus der Barmherzigen Brüder
city: Ulm
country: Germany
facility: Ulm Universitätsklinikum
city: Gdansk
country: Poland
facility: Gdansk Uniwersyteckie Centrum Kliniczne
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Roxana Mehran, MD
role: STUDY_CHAIR
References: