Autus Valve Early Feasibility Study

Study Overview
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Brief Summary
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Prospective, single-arm, multi-center study to evaluate safety and preliminary effectiveness of the Autus Size-Adjustable Valve in pediatric patients aged 18 months to 16 years requiring surgical pulmonary valve replacement. The Autus Valve may be expanded pre-implant to match the subject's body size. Subjects will be evaluated prior to the Autus Valve implant procedure, immediately post-implant, at hospital discharge, 30 days, 6 and 12 months, and annually through 5 years. The Autus Valve may be expanded post-implant via transcatheter balloon dilation to accommodate growth of the subject. In subjects who undergo a post-implant valve expansion, follow-up will continue for a minimum of 1 year after the post-implant valve expansion procedure.

Official Title
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Autus Size-Adjustable Valve for Surgical Pulmonary Valve Replacement Early Feasibility Study

Conditions
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Congenital Heart Disease

Intervention / Treatment
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* Device: Pulmonary Valve Replacement Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Candidates must meet all of the following inclusion criteria to be considered for enrollment in this study. Age 18 months to 16 years. Male or female. Subject has a native or repaired right ventricular outflow tract. Subject has been recommended for surgical pulmonary valve replacement by treating clinical team (cardiologist and cardiac surgeon). Subject has at least one of the following echocardiographic findings: Severe pulmonary stenosis (defined as RV to PA peak instantaneous gradient ≥60 mmHg); Moderate or greater pulmonary regurgitation (defined as (vena contracta jet width/square root of BSA) ≥2.98 mm/m2). Moderate or greater pulmonary stenosis plus moderate or greater pulmonary regurgitation. Subject's body size is suitable for implantation of a study device ranging from 12.7 to 22 mm (internal diameter). Subject's pulmonary artery length is adequate for implantation of the study device. Subject and parent/legal representative, where appropriate, are willing to provide informed written consent. Subject and parent/legal representative, where appropriate, and treating physician agree that the subject will return for, and comply with, all required study assessments and follow-up visits. Exclusion Criteria: Candidates will be excluded from the study if any of the following conditions are met: Subject requires valve replacement in a non-pulmonary position. Subject has a prosthetic valve at other valve position or will need a prosthetic valve at other valve position (i.e., anticipate additional valve replacements needed within 3 years). Subject has pulmonary arterial hypertension (defined as mean PA pressure ≥25 mmHg). Subject has pulmonary atresia and major aortopulmonary collaterals. Subject has significant peripheral pulmonary artery stenosis. Subject requires a concomitant non-cardiac surgical procedure. Subject has an active infection requiring current antibiotic therapy (if temporary illness, subject may be a candidate 4 weeks after discontinuation of antibiotics). Subject has active endocarditis or a history of infective endocarditis. Subject has renal insufficiency as determined by a serum creatinine (S-Cr) level ≥2.5 mg/dL within 60 days prior to the Screening Visit, or has end-stage renal disease. Subject has leukopenia (defined as a white blood cell (WBC) count <3.5 x 103/µL) Subject has acute or chronic anemia (defined as hemoglobin (Hgb) <10.0 g/dl or 6 mmol/L). Subject has thrombocytopenia (defined as platelet count <50 x 103/µL. Subject has a known hypersensitivity to anticoagulants and antiplatelet drugs. Subject has a known autoimmune disease or receives immunosuppressant and/or immunostimulant drugs. Subject needs emergency cardiac or vascular surgery or intervention. Subject has, in the opinion of the Investigator, a life expectancy of less than 5 years. Subject or parent/legal representative refuses blood transfusions. Subject has medical, social or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures. Subject is participating in an investigational study of a new drug, biologic or device at the time of study screening.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 16 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: Autus Valve Arm<br>Pulmonary Valve Replacement Surgery with the Autus Valve | Device: Pulmonary Valve Replacement Surgery<br>* Pulmonary valve replacement surgery with the Autus Valve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Valve Implantation Primary Safety Endpoint | Composite Endpoint: Freedom from a device-related complication at 12 months post-valve implantation as adjudicated by an independent Clinical Events Committee (CEC), including: Death; Valve thrombosis; Thromboembolism. | 12 months | 
| Post-implant Valve Expansion Primary Safety Endpoint | Composite Endpoint: Freedom from post-implant valve expansion procedure-related complication at 30 days post-valve expansion as adjudicated by an independent CEC: Death; Extracorporeal membrane oxygenation (ECMO) support; Unplanned intervention (surgical or transcatheter); Major hemorrhage | 30 days | 
| Valve Implantation Primary Effectiveness Endpoint | Clinically acceptable hemodynamic performance at 12 months, defined as less than moderate pulmonary regurgitation, as assessed by the Echo Core Lab (ECL) via transthoracic echocardiogram (TTE). | 12 Months | 
| Post-implant Valve Expansion Primary Effectiveness Endpoint | Clinically acceptable hemodynamic performance at 6 months post-valve expansion procedure, as assessed by the ECL via TTE, defined as: Less than moderate pulmonary regurgitation (PR) by Doppler echocardiography; Right ventricle (RV) to pulmonary artery (PA) peak instantaneous gradient lower than clinical criteria for post-implant valve expansion: In setting of normal RV function: RV to PA peak instantaneous gradient <40 mmHg; In setting of RV systolic dysfunction (mild or greater): RV to PA peak instantaneous gradient <30 mmHg; In setting of clinical symptoms (Modified Ross class II or above): RV to PA peak instantaneous gradient <30 mmHg. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Safety Endpoint - Device-related | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Device-related complication post-valve implantation composite endpoint, including: death, valve thrombosis or thromboembolism (evaluation at 12 months is considered the valve implantation primary safety endpoint) | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Mortality | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Mortality, including: all cause, cardiac-related, procedure-related and device-related | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Thrombosis | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Thrombosis | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Thromboembolism | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Thromboembolism | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Reintervention | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Reintervention, including all-cause unplanned reintervention (surgical or transcatheter) and reoperation | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Major Hemorrhage | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Major Hemorrhage | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Endocarditis | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Endocarditis | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Hemolysis | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Hemolysis | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Structural Valve Deterioration | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Structural valve deterioration | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Valve/stent Frame Fracture | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Valve/Stent Frame Fracture | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Device Explantation | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Device explantation | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Safety Endpoint - Adverse Events (AE) | The following secondary safety endpoint will be evaluated at 30 days, 6 and 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation by an Independent CEC: • Adverse events (AE) | 30 days, 6 months, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation | 
| Secondary Effectiveness Endpoint-Valve Implant Acute Procedural Success | To meet the definition of success, all the parameters listed below must be achieved, as assessed by Sites using direct pressure measurements and/or transesophageal echo (TEE): RV to PA peak systolic pressure gradient <40 mmHg (direct pressure measurement); None or trivial pulmonary regurgitation (assessed via TEE); No paravalvular leak (assessed via TEE). | Immediately Post-Valve Implant Procedure | 
| Secondary Effectiveness Endpoint - Post-Implant Valve Expansion Acute Procedural Success | To meet the definition of success, at least one of the parameters listed below must be achieved after each post-implant valve expansion is performed, assessed during the same catheterization procedure: RV to aortic systolic pressure ratio: ≤0.5. Peak-to-peak RV to PA systolic pressure gradient: ≤15 mmHg; Peak-to-peak RV to PA systolic pressure gradient: ≥50% reduction (pre vs post valve expansion). | Immediately after each post-implant valve expansion procedure | 
| Secondary Effectiveness Endpoint - Change in Cardiac Index Post-Implant Valve Expansion | The percent change in cardiac index (pre- versus post-valve dilation) will be determined for each post-implant valve expansion performed using the Direct Fick Method of measuring Cardiac Output. | Immediately after each post-implant valve expansion procedure | 
| Secondary Effectiveness Echo-Related Endpoint - Pulmonary Regurgitation | Pulmonary regurgitation status categorized as none, trivial, mild, moderate, severe as evaluated by the Echo Core Laboratory. | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - Freedom from Moderate or Greater Pulmonary Regurgitation | Freedom from moderate or greater pulmonary regurgitation, as evaluated by the Echo Core Laboratory. | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - Pulmonary Stenosis Status | Pulmonary stenosis status categorized as none/trivial, mild, moderate, severe, as evaluated by the Echo Core Laboratory. | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - RV to PA systolic pressure gradient - assessed via Continuous Wave (CW) Doppler | RV to PA systolic pressure gradient assessed via Continuous Wave (CW) Doppler (peak and mean instantaneous gradient) | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - RV to PA systolic pressure gradient - assessed via Pulsed Wave (PW) Doppler | RV to PA systolic pressure gradient - multi-level (subvalvar, valvar, supravalvar) assessment via Pulsed Wave (PW) Doppler (peak and mean instantaneous gradient) | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - Paravalvular Leak | Paravalvular Leak | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - Right Ventricular Measures | Right ventricular measures, including mass, volume, pressure and function | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Echo-Related Endpoint - Left Ventricular Measures | Left ventricular measures, including mass, volume, and function | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. | 
| Secondary Effectiveness Endpoint - Modified Ross Functional Classification | Modified Ross Functional Class as assessed by the Site Investigators | 30 days, 6 months, 12 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion. |