Comparing cerebral embolic protection devices during TAVR for severe aortic stenosis

Cerebral Protection in Transcatheter Aortic Valve Replacement: the PROTEMBO Trial

This study is testing whether the ProtEmbo device can better protect the brain during a heart valve replacement procedure for people with severe aortic stenosis compared to other methods.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Protembis GmbH (Industry-sponsored)
• Locations: 18 sites (Los Angeles, California and 17 other locations)
• Trial ID: NCT05873816 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of the ProtEmbo Cerebral Embolic Protection device compared to a hybrid control group that includes no device and the Sentinel device in patients with severe symptomatic aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR). Participants will be randomly assigned to one of three groups and will undergo MRI scans to assess new cerebral lesions before and after the procedure. The study will track major adverse cardiac and cerebrovascular events over a 30-day follow-up period. The goal is to determine if the ProtEmbo device offers significant advantages in preventing complications associated with TAVR.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with severe symptomatic aortic stenosis who are recommended for TAVR.

Not a fit: Patients who are women of child-bearing potential or have anatomical issues preventing access for the procedure may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved safety and outcomes for patients undergoing TAVR by reducing the risk of cerebral embolic events.

How similar studies have performed: Other studies have explored cerebral embolic protection during TAVR, but the specific use of the ProtEmbo device in this context is novel.

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.

Where this trial is running

Los Angeles, California and 17 other locations

• Cedars-Sinai Medical Center — Los Angeles, California, United States (Recruiting)
• BayCare Health System / Morton Plant Hospital — Clearwater, Florida, United States (Recruiting)
• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
• Saint Luke's Hospital of Kansas City — Kansas City, Missouri, United States (Recruiting)
• Washington University - St. Louis — St Louis, Missouri, United States (Recruiting)
• State University of New York at Buffalo — Buffalo, New York, United States (Recruiting)
• NYU Langone — New York City, New York, United States (Recruiting)
• Mount Sinai Hospital — New York City, New York, United States (Recruiting)
• Columbia University Medical Center / NYPH — New York, New York, United States (Recruiting)
• Weill Medical College / Cornell University — New York, New York, United States (Recruiting)
• University of Texas, Memorial Hermann Hospital — Houston, Texas, United States (Recruiting)
• University of Virginia, Charlottesville — Charlottesville, Virginia, United States (Recruiting)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)
• Dresden Herzzentrum — Dresden, Germany (Recruiting)
• Lübeck Universitätsklinikum Schleswig-Holstein Campus — Lübeck, Germany (Recruiting)
• Trier Krankenhaus der Barmherzigen Brüder — Trier, Germany (Recruiting)
• Ulm Universitätsklinikum — Ulm, Germany (Recruiting)
• Gdansk Uniwersyteckie Centrum Kliniczne — Gdansk, Poland (Recruiting)

Study contacts

• Study coordinator: Nawzer Mehta, PhD

Conditions Severe Aortic Valve Stenosis; TAVR; Cerebral embolic protection