The PROTEMBO Trial

Cerebral Protection in Transcatheter Aortic Valve Replacement: The PROTEMBO Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Severe Aortic Valve Stenosis
• Intervention / Treatment: Device: ProtEmbo - Cerebral Embolic Protection; Device: Sentinel - Cerebral Embolic Protection

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.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nawzer Mehta, PhD; Phone Number: +1 707 293 5435; Email: nm@protembis.com
• Study Contact Backup: Name: Karl von Mangoldt; Phone Number: +49-178-8164564; Email: kvm@protembis.com

Study Locations

• United States
  • Florida
    • Clearwater, Florida, United States, 33756
      • Recruiting
      • BayCare Health System / Morton Plant Hospital
      • Contact: Beth Schelle; Email: Mary.Schelle@baycare.org
      • Principal Investigator: Joshua Rovin, MD
      • Contact: Susan Fisher; Email: susan.fisher1@baycare.org
  • New York
    • Buffalo, New York, United States, 14203
      • Recruiting
      • State University of New York at Buffalo
      • Contact: Courtney Bishop; Email: cabishop@buffalo.edu
      • Principal Investigator: Vijay Iyer, MD
      • Contact: Shannon Allen; Email: seallen@buffalo.edu
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center / NYPH
      • Contact: Kate Dalton, MS; Phone Number: 347-514-3366; Email: keb2114@cumc.columbia.edu
      • Principal Investigator: Vivian Ng, MD
      • Sub-Investigator: Susheel Kodali, MD
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Medical College / Cornell University
      • Contact: Dolores Reynolds; Email: dtr2001@med.cornell.edu
      • Principal Investigator: Shin Chiu Wong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ProtEmbo - Cerebral Embolic Protection; Subjects will undergo TAVR following placement of the ProtEmbo cerebral embolic protection device.	Device: ProtEmbo - Cerebral Embolic Protection; Subjects will undergo TAVR following placement of the ProtEmbo cerebral embolic protection device.
Active Comparator: Sentinel - Cerebral Embolic Protection; Subjects will undergo TAVR following placement of the Sentinel cerebral embolic protection device.	Device: Sentinel - Cerebral Embolic Protection; Subjects will undergo TAVR following placement of the Sentinel cerebral embolic protection device.
No Intervention: Control Arm; Subjects will undergo TAVR without embolic protection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACCE at 30 days	Occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 days defined as all-cause mortality, all stroke, life-threatening or disabling bleeding, major vascular complications, and acute kidney injury (stage 2 or 3) as defined by VARC-3.	Up to Day 30 post procedure
Total new lesion volume	Total new lesion volume (TNLV) in the brain assessed by diffusion weighted magnetic resonance imaging (DW-MRI) at 36 ±12 hours.	36 ±12 hours post TAVR procedure

Collaborators and Investigators

• Sponsor: Protembis GmbH
• Investigators: Study Chair: Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: TAVR; Cerebral embolic protection
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis
• Other Study ID Numbers: CIP_00250

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes