Transmural Systems Transcaval Closure Device for Transcaval Access Ports During Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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Background: Transcatheter aortic valve replacement (TAVR) is a non-surgical alternative to standard surgical aortic valve replacement. Not all patients are eligible for TAVR using standard access through the artery in the groin, because the artery is too small or too diseased. In this study, TAVR is performed using a new technique called transcaval access. The catheter is placed in the artery deep in the body by crossing through the wall of a deep vein. The connection between that vein and the aorta is closed with a new metallic device they are testing. This is called a transcaval closure device (TCD). Objective: To test the safety and early feasibility of closure of transcaval aortic access sites using the TCD after TAVR. Eligibility: Adults ages 21 and older undergoing TAVR for whom the procedure cannot be performed safely by the standard artery approach Design: Participants will be assessed by heart experts including cardiologists and surgeons. Participants will have TAVR by the transcaval approach. A small catheter will be passed between the largest vein in the body and the nearby largest artery (aorta), inside the abdomen. Through this catheter, the TAVR will be implanted in the usual way. After, doctors will implant the TCD by catheter to close the hole made in the aorta. Participants will be X-rayed. A dye will be injected to view the TCD device. Participants will get standard TAVR care afterwards. They will have physical exams, blood tests, and scans. Participants will have a follow-up scan within 1 month and after 12 months. Participants will have follow-up visits and phone calls 6 and 12 months after the procedure.

Detailed Description
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Transcaval access to the abdominal aorta from the neighboring inferior vena cava (IVC) enables transcatheter aortic valve replacement (TAVR) in patients not eligible for femoral artery access. Currently the procedure is performed using devices, off-label, designed and marketed to close holes inside the heart and great vessels, manufactured by Abbott St Jude (Amplatzer Duct Occluder and Amplatzer Muscular VSD Occluder). Because these Amplatzer occluders are not designed to close transcaval access sites, they may not completely prevent bleeding. This is an early feasibility study (EFS) evaluation of a purpose-built closure device for transcaval access. The device, the Transcaval closure device (TCD) will be evaluated for safety and performance to close transcaval access sites in patients ineligible for femoral artery access for TAVR.

Official Title
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Early Feasibility Evaluation of Transmural Systems Transcaval Closure Device (TCD) for Transcaval Access Ports During Transcatheter Aortic Valve Replacement (TAVR)

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Device: Transcaval closure device (TCD)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Consents to participate in this study and all related clinical follow-up procedures Adults age greater than or equal to 21 years Undergoing transcatheter aortic valve replacement (TAVR) based on the clinical assessment of the multidisciplinary heart team Ineligible for femoral artery access for the selected transcatheter heart valve (THV) according to the THV manufacturer instructions for use. (Note Corevalve Evolut R: greater than or equal to 5mm; Evolut PRO 23, 26, 29 mm valves and Evolut R 34 mm: greater than or equal to 5.5 mm; Edwards Sapien 3, 23-26mm: 5.5 mm; Edwards Sapien 3, 29mm: 6.0mm; Anatomic ineligibility also considers patient-specific pattern of iliofemoral calcium and tortuosity.) Eligible for transcaval access based on Core lab analysis of the baseline abdomen/pelvis CT indicating a calcium-free target window on the abdominal aorta; a target greater than or equal to 15mm from the lowest main renal artery or aorto-iliac bifurcation; no important interposed structures; a projected intravascular centerline distance from the lower femoral head to the target at least 5cm less than the intended THV introducer sheath; patient celiac or superior mesenteric artery Aorta diameter greater than or equal to 11mm at the target crossing site Concordance of the study eligibility committee EXCLUSION CRITERIA: High risk features on baseline CT including porcelain aorta (confluent calcification); pedunculated aortic atheroma; or leftward aortic angel greater than or equal to 20 degrees with regard to vertical. Renal dysfunction limiting follow-up contrast-enhanced CR (estimated glomerular filtration rate, eGFR less than 30mL/min/1.73m^2 if not already on renal replacement therapy) Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcaval access and closure with the transcaval closure device (TCD) test article.<br>All participants undergo transcaval access for transcatheter aortic valve replacement (TAVR) followed by implantation of the transcaval closure device (TCD). | Device: Transcaval closure device (TCD)<br>* Transcaval access and closure using the Transmural Transcaval Closure Device (TCD) at the time of medically-necessary transcatheter aortic valve replacement (TAVR).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Technical Success of Delivery of the Transcaval Closure Device (TCD) | Number of participants with technical success of delivery of the transcaval closure device (TCD) All of the following must be present for technical success: Alive Successful delivery of the TCD, and retrieval of the TCD delivery system Deployment and correct positioning of a single intended TCD. Repositioning and recapture of the device, if needed, is not classified as failure. No additional unplanned or emergency surgery or re-intervention related to the TCD or delivery system Adjunctive balloon aortic tamponade is permissible and consistent with technical success | 1 minute following procedure discharge (Exit from the catheterization laboratory) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Closure Success of the Transcaval Closure Device (TCD) | Number of Participants With Technical Closure Success of Delivery of the Transcaval Closure Device (TCD). This secondary endpoint is a composite of the primary endpoint and hemostasis of the transcaval aortic access site. All of the following must be present for Closure Success: Alive Successful delivery of the TCD, and retrieval of the TCD delivery system Deployment and correct positioning of a single intended TCD. Repositioning and recapture of the device, if needed, is not classified as failure. No additional unplanned or emergency surgery or re-intervention related to the TCD or delivery system. Adjunctive balloon aortic tamponade is permissible and consistent with technical success Complete occlusion of the aortocaval fistula on the completion aortogram. | 1 minute following procedure discharge (Exit from the catheterization laboratory) | 
| Number of Participants Who Experienced Device Success of the Transcaval Closure Device (TCD) | A key performance endpoint is the number of participants who experienced device success of the transcaval closure device (TCD). All of the following must be present for device success: Alive or Death unrelated to transcaval access or TAVR Original intended TCD in place No additional surgical or interventional procedures related to access or the device after exit from the cath lab Intended performance of the TCD, including all of: Structural Performance: No migration, embolization, detachment, fracture, hemolysis, or endarteritis related to the TCD Hemodynamic performance: No abdominal aortic obstruction caused by the TCD implant Absence of para-device complications (large retroperitoneal hematoma, pseudoaneurysm, distal thromboembolism, or pulmonary thromboembolism) | 30 days and 12 Months | 
| Number of Participants That Experienced Procedural Success | Number of participants that experienced safety endpoint of procedural success following transcaval closure device (TCD) at day 30. All of the following must be present for procedural success: Device success No device-related Serious Adverse Events, defined as VARC-2 life-threatening bleeding, major vascular or cardiac complications related to the TCD requiring unplanned reintervention or surgery (such as covered stent implantation at the transcaval access site) | 30 Days | 
| Number of Participants Requiring Covered Stent Implantation as a Normal Provisional Part of the Procedure | Number of participants requiring covered stent implantation as a normal provisional part of the procedure assessed during the procedure. | During procedure, procedure may last from 2 to 4 hours | 
| Number of Participants With Covered Stent Implantation at the Transcaval Closure Device Implantation Site | Number of participants with covered stent implantation at the transcaval closure device (TCD) implantation site | During procedure, procedure may last from 2 to 4 hours | 
| Number of Participants Final Acute Aorto-caval Fistula Score | Number of Participants final acute aorto-caval fistula score at procedure completion. Scoring is defined as: Type 0=occlusion, Type 1=patent fistula, Type 2=cruci-form fistula pattern, Type 3=extravasation. A score of 0 is associated with complete occlusion at the transcaval closure device (TCD) site while a higher score is associated with incomplete occlusion at the TCD site. | 30 Days | 
| Number of Participants Who Experienced Modified Valve Academic Research Consortium-2 Vascular Complications | Participants who experienced Minor or Major modified Valve Academic Research Consortium-2 (VARC-2) vascular complications. Major is defined as: Aortic dissection or aortic rupture; Access site-related arterial or venous injury THAT RESULTS IN death, hemodynamic compromise, life-threatening, extensive; or major bleeding, visceral ischemia, neurological impairment; Distal embolization requiring surgery or resulting in amputation or irreversible end-organ damage; severe access site vascular complication Minor is defined as: Access site-related arterial or venous injury THAT DOES NOT RESULT IN death, hemodynamic compromise, life-threatening, extensive; or major bleeding, visceral ischemia, neurological impairment; Distal embolization treated with embolectomy and/or thrombectomy not resulting in amputation or irreversible end-organ damage; Any unplanned endovascular stenting or unplanned surgical intervention not meeting the criteria for a major vascular complication; Vascular repair | 30 days | 
| Number of Participants Who Experienced Modified Valve Academic Research Consortium-2 Bleeding Complications | Number of Participants Who Experienced Major or Life-threatening Modified Valve Academic Research Consortium-2 (VARC-2) bleeding complications at 30 days Major defined as: Corrected drop in the hemoglobin of >=3.0 g/dl AND does not meet criteria of life-threatening or extensive bleeding; Requiring transfusion of >=3 U of whole blood or packed RBCs AND does not meet criteria of life-threatening or extensive bleeding. Life-threatening defined as: Intracranial requiring surgery or intervention; Intraspinal requiring surgery or intervention; Intraocular requiring surgery or intervention; Pericardial requiring surgery or intervention; Intramuscular with compartment syndrome; Bleeding causing hypovolemic shock or hypotension or requiring significant doses of vasopressors or surgery | 30 Days | 
| Number of Participants Who Experienced Major Adverse Cardiovascular Events | Number of Participants Who Experienced Major Adverse Cardiovascular Events (MACE) Major adverse cardiovascular events (MACE), defined as VARC-2 Early Safety composite: No mortality, stroke, life-threatening bleeding, acute kidney injury (AKI) stage 2+, major vascular complication, and valve-related complication. | Day 30 | 
| Number of Participants With Closure Success of Delivery of the Transcaval Closure Device (TCD) | Number of Participants With Closure Success of Delivery of the Transcaval Closure Device (TCD). All of the following must be present for Closure Success: Alive or Death unrelated to transcaval access or TAVR Successful delivery of the TCD, and retrieval of the TCD delivery system Deployment and correct positioning of a single intended TCD. Repositioning and recapture of the device, if needed, is not classified as failure. No additional unplanned or emergency surgery or re-intervention related to the TCD or delivery system. Adjunctive balloon aortic tamponade is permissible and consistent with technical success Complete occlusion of the aortocaval fistula on the completion aortogram. | 30 Days and 12 Months | 
| All-Cause Mortality | All-cause mortality, as categorized by cardiovascular vs non-cardiovascular, peri- vs non-periprocedural, regardless of attribution to Transcaval Closure Device (TCD) | 30 Days | 
| Number of Participants With Aorto-caval Fistula Patency Assessed by Angiography and Arterial-phase Follow-up Computed Tomography | Number of participants with aorto-caval fistula patency at each timepoint, assessed combining completion angiography and arterial-phase follow-up Computed tomography (CT). | Day 30, 12 months | 
| Number of Participants Who Experienced Acute Kidney Injury Stage 2 or 3 | Number of participants who experienced acute kidney injury (AKI) stage 2 or 3 using the Valve Academic Research Consortium (VARC). AKI using the VARC definition: Stage 2: increase in serum creatinine to 200-300% (2.0-3.0 times increase compared to baseline) or increase of >0.3 mg/dl (>26.4 mmol/L) but <4.0 mg/dl (<354 mmol/L) Stage 3: increase in serum creatinine to ≥300% (>3 times increase compared to baseline) or serum creatinine of ≥4.0 mg/dl (≥354 mmol/L), with acute increase of ≥0.5 mg/dl (44 mmol/L) | 30 Days | 
| Number of Participants That Are Free From Infection Related to the Transcaval Closure Device | Number of participants that experience freedom from infection related to the Transcaval Closure Device (TCD) at each time point | Day 30, 12 Months | 
| Number of Participants That Experience Thrombocytopenia and is Attributable to Residual Aorto-caval Fistula or the Transcaval Closure Device | Number of participants that experience Thrombocytopenia as defined as < 50,000 and is attributable to residual aorto-caval fistula or the Transcaval Closure Device (TCD) | 30 Days | 
| Number of Participants Who Experience Hemolysis and is Attributable to Residual Aorto-caval Fistula or the Transcaval Closure Device | Number of participants who experience hemolysis and is attributable to residual aorto-caval fistula or the Transcaval Closure Device (TCD) | 30 Days | 
| Participant Cumulative Computed Tomography Analysis of Device | Participant cumulative Computed tomography (CT) analysis of device. As defined by: Device position; Device integrity; Aortocaval tract pseudo-aneurysm; Aortic pseudoaneurysm; Retroperitoneal hematoma grade (stranding {=absent and not evidence of overt bleeding;} small; moderate; larger); Intracaval mass or thrombus; Aortic dissection and inferred relatedness to TCD (adjacent to access port) or procedure (remote to access port) | Day 30 | 
| Number of Participants Enrolled Greater Than 65 Years | Outcomes of subjects greater than 65 years (i.e. eligible for Medicare based on age), to determine generalizability to the Medicare population | Enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcatheter, Transcaval, Bioprosthesis, Closure Device, Aortic Stenosis