Autus Valve Pivotal Study

Congenital Heart Disease Clinical Trial

Official title:

Autus Size-Adjustable Valve for Surgical Pulmonary Valve Replacement Pivotal Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05006404
• Other study ID #: AUT-CP-001
• Status: Recruiting
• Phase: N/A
• Start date: February 5, 2024
• Est. completion date: February 2036

Study information

• Verified date: February 2024
• Source: Autus Valve Technologies, Inc.
• Contact: Sophie-Charlotte Hofferberth, MD.
• Phone: 617-390-6468
• Email: shofferberth[@]autusvalve.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, single-arm, multi-center study to evaluate safety and 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 months, and annually through 10 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 2036
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 16 Years

Eligibility

Inclusion Criteria:

Candidates must meet all of the following inclusion criteria to be considered for enrollment in this study.

1. Age 18 months to 16 years.

2. Male or female.

3. Subject has a native or repaired right ventricular outflow tract.

4. Subject has been recommended for surgical pulmonary valve replacement by treating clinical team (cardiologist and cardiac surgeon).

5. Subject has at least one of the following echocardiographic findings:

1. Severe pulmonary stenosis (defined as RV to PA peak instantaneous gradient =60 mmHg);

2. Moderate or greater pulmonary regurgitation;

3. Moderate or greater pulmonary stenosis plus moderate or greater pulmonary regurgitation.

6. Subject's body size is suitable for implantation of a study device ranging from 12.7 to 22 mm (internal diameter).

7. Subject and parent/legal representative, where appropriate, are willing to provide informed written consent.

8. 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:

1. Subject requires valve replacement in a non-pulmonary position.

2. 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).

3. Subject has pulmonary arterial hypertension (defined as mean PA pressure =25 mmHg).

4. Subject has pulmonary atresia and major aortopulmonary collaterals.

5. Subject has significant peripheral pulmonary artery stenosis.

6. Subject has an active infection requiring current systemic antibiotic therapy (if temporary illness, subject may be a candidate 4 weeks after discontinuation of antibiotics).

7. Subject has active endocarditis or a history of infective endocarditis.

8. 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.

9. Subject has leukopenia (defined as a white blood cell (WBC) count <3.5 x 103/µL)

10. Subject has acute or chronic anemia (defined as hemoglobin (Hgb) <10.0 g/dl or 6 mmol/L).

11. Subject has thrombocytopenia (defined as platelet count <50 x 103/µL.

12. Subject has a known hypersensitivity to anticoagulants and antiplatelet drugs.

13. Subject has a known autoimmune disease or receives immunosuppressant and/or immunostimulant drugs that the Investigator or Eligibility Screening Committee (ESC) believes may negatively affect study outcomes.

14. Subject needs emergency cardiac or vascular surgery or intervention.

15. Positive pregnancy test prior to valve implant procedure in female subjects who have had their first menses.

16. Subject has, in the opinion of the Investigator, a life expectancy of less than 5 years.

17. Subject or parent/legal representative refuses blood transfusions.

18. Subject has medical, social or psychosocial factors that, in the opinion of the Investigator or ESC, could impact safety or compliance with study procedures.

19. Subject is participating in an investigational study of a new drug, biologic or device at the time of study screening.

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

Device:
• Pulmonary Valve Replacement Surgery
Pulmonary valve replacement surgery with the Autus Valve

Locations

Country	Name	City	State
United States	University of Michigan - Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Columbia University Irving Medical Center/New York Presbyterian Morgan Stanley Children's Hospital	New York	New York
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Autus Valve Technologies, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other Safety Outcome - Composite	The following other safety outcome will be evaluated at 6 months, and annually through 10 years post-valve implantation by an independent Clinical Events Committee. The composite outcome includes device-related: Death; Valve thrombosis requiring intervention; Symptomatic thromboembolism.	6 months and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Mortality	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Mortality, including: all cause, cardiac-related, procedure-related and device-related	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Valve Thrombosis	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Valve thrombosis	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Thromboembolism	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Thromboembolism	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Cardiac or Valve Intervention	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Other cardiac or valve intervention (surgical or transcatheter)	30 days, 6 months, and annually through a minimum of 510 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Major Hemorrhage	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Major hemorrhage	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Endocarditis	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Endocarditis	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Hemolysis	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Hemolysis	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Device Explantation	The following measure will be evaluated by an independent Clinical Events Committee at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Device explantation	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Adverse Events (AE)	The following measure will be reported at 30 days, 6 months, and annually through 10 years post-valve implantation. Subjects that undergo valve expansion in year 10 after device implantation will be followed for an additional year.; • Adverse events	30 days, 6 months, and annually through a minimum of 10 years and up to 11 years post-valve implantation
Other	Other Safety Outcome - Valve/Stent Fracture	An independent Medical Reviewer will review post-implant chest x-rays to assess for valve/stent fracture. Chest x-rays will be performed at the following timepoints: post-valve implantation at hospital discharge, and annually through 5 years post-valve implantation. If a post-implant valve expansion procedure is performed, chest x-rays will be performed at hospital discharge and 12 months post-procedure.	pre-discharge, 12 months, and annually through a minimum of 5 years and up to 6 years post-valve implantation. Subjects that undergo post-implant valve expansion will be evaluated pre-discharge and at 12 months post-valve expansion.
Other	Other Effectiveness Outcome - 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
Other	Other Effectiveness Outcome - Pulmonary Regurgitation Grade	Pulmonary regurgitation grade categorized as none, trivial, mild, moderate, severe as evaluated by the Echo Core Laboratory.	Baseline, 30 days, 6 months, and annually through 10 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion.
Other	Other Effectiveness Outcome - Pulmonary Stenosis Grade	Pulmonary stenosis grade categorized as none/trivial, mild, moderate, severe, as evaluated by the Echo Core Laboratory.	Baseline, 30 days, 6 months, and annually through 10 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion.
Other	Other Effectiveness Outcome - Right Ventricular Measures	Right ventricular (RV) measures, including RV dimension and strain will be evaluated by the Echo Core Laboratory.	Baseline, 30 days, 6 months, and annually through 5 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion.
Other	Other Effectiveness Outcome - Left Ventricular Measures	Left ventricular (LV) measures, including LV ejection fraction and strain will be evaluated by the Echo Core Laboratory.	Baseline, 30 days, 6 months, and annually through 10 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion.
Other	Other Effectiveness Outcome - Modified Ross Functional Classification	Modified Ross Functional Class as assessed by the Site Investigators	Baseline, 30 days, 6 months, and annually through 10 years post-valve implant and 30 days, 6 months, and 12 months post-valve expansion.
Other	Other Effectiveness Outcome - PedsQL - Cardiac Module	The Pediatric Qualify of Life Inventory (PedsQL) Cardiac Module will be administered by Site Personnel.	Baseline, 6 months and annually through 10 years post-valve implantation. Subjects that undergo post-implant valve expansion will be evaluated pre-valve expansion, and at 6 and 12 months post-valve expansion.
Other	Other Post-Implant Valve Expansion Safety Outcome - Composite	Composite Endpoint: Freedom from device-related complication through 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 after each post-implant valve expansion procedure
Other	Other Post-Implant Valve Expansion Effectiveness Outcome - 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
Other	Other Post-Implant Valve Expansion Effectiveness Outcome - Hemodynamic Performance	Clinically acceptable hemodynamic performance at 6 months post-valve expansion procedure, as assessed by the Echo Core Laboratory via TTE, defined as: Less than moderate pulmonary regurgitation (PR) by Doppler echocardiography; Transvalvular gradient (assessed by CW Doppler) at 6-months is lower than the pre-expansion gradient.	6 months after each post-implant valve expansion procedure
Primary	Valve Implantation Primary Safety Endpoint	Composite Endpoint: Freedom from a device-related complication through 30 days post-valve implantation as adjudicated by an independent Clinical Events Committee (CEC), including: Death; Valve thrombosis requiring intervention; Symptomatic thromboembolism.	30 Days post-valve implantation
Primary	Valve Implantation Primary Effectiveness Endpoint	Acceptable hemodynamic performance at 6 months post-valve implantation, as assessed by the Echocardiography Core Laboratory or Clinical Events Committee, defined as: A mean RVOT gradient less than or equal to 40 mmHg and; Less than moderate pulmonary regurgitation by transthoracic echo and; No Autus Valve reintervention except for valve expansion to address prosthesis-patient mismatch.	6 Months post-valve implantation