TIARA-I: Early Feasibility Study of the Neovasc Tiara™ Mitral Valve System

• Sponsor: Neovasc Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02276547
• Collaborator: (none)
• Enrollment: 27
• Locations: 10
• Arm: 1
• Duration (Months): 122.1
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and initial performance of the Neovasc Tiara Mitral Transcatheter Heart Valve with the Tiara Transapical Delivery System.

Condition or Disease	Intervention/Treatment	Phase
Mitral Valve Regurgitation	Device: Mitral valve replacement	N/A

Detailed Description

This is an international, multicenter, single arm, prospective, Early Feasibility Clinical Study to evaluate the safety and performance of the Neovasc Tiara Mitral Valve System in subjects with symptomatic severe mitral regurgitation requiring mitral valve replacement who are at high risk for open chest surgery.

A maximum of 30 subjects will be implanted in this study at a maximum of 10 sites. A maximum of 15 subjects will be implanted in the United States.

Subjects satisfying the inclusion criteria and exclusion criteria will be enrolled to receive the Neovasc Tiara Mitral Transcatheter Heart Valve with the Tiara Delivery System via a transcatheter mitral valve replacement (TMVR) procedure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Feasibility Study of the Neovasc Tiara™ Mitral Transcatheter Heart Valve With the Tiara™ Transapical Delivery System
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Jan 6, 2020
• Anticipated Study Completion Date: Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Transcatheter mitral valve replacement with the TIARA valve and transapical delivery system	Device: Mitral valve replacement; Transcatheter mitral valve replacement; Other Names: TIARA Mitral Transcatheter Heart Valve, TIARA Transapical Delivery System

Outcome Measures

Primary Outcome Measures

1. Freedom From All-cause Mortality and Major Adverse Events [From the time of implant procedure to 30 days or hospital discharge (whichever is later)]

   Defined as disabling stroke, myocardial infarction, renal failure requiring dialysis, life-threatening bleeding, and cardiac surgical or transcatheter reintervention

Secondary Outcome Measures

1. Number and Percentage of Subjects With All-cause Mortality, Disabling Stroke, Myocardial Infarction, Renal Failure Requiring Dialysis, Life-threatening Bleeding and Cardiac Surgical or Transcatheter Reintervention [30 days, 90 days, 180 days and annually to five years]

2. Individual 30 Day Rates of Device and Procedure Related Major Adverse Events [30 days]

   All mortality All stroke Residual MR > mild (1+) Life threatening bleeding Acute kidney injury Grade 3 New pacemaker/LBBB Coronary occlusion/myocardial infarction Urgent/emergent surgery or reintervention

3. Number and Percentage of Subjects With Progression of Heart Failure [One year]

   Readmission for Heart Failure Need for Heart Failure device implantation Cardiac transplantation Listing for transplantation

4. Device Success; Delivery and Deployment of the Device in the Correct Position and Retrieval of Delivery Catheter [Post procedure, discharge, 30 days, 90 days, 180 days and annually for five years]

   Mitral regurgitation < moderate (2+) Effective valve orifice area ≥ 1.5 cm2 as assessed by post-procedural echocardiogram Mitral Valve gradient < 5 mmHg No migration No fracture No endocarditis Stroke free No additional valve/access related interventional or surgical procedures

5. Performance [30 days, 90 days, 180 days and annually for five years]

   Clinical performance as measured by NYHA Functional Class, 6MWT, and the KCCQ Hemodynamic performance as assessed by echocardiography: mean MV gradient, mitral regurgitation, effective orifice area of the MV, LV systolic and diastolic dimensions as well as volume Stroke free survival Original intended device in place No additional valve/access-related interventional or surgical procedures

6. Days Alive and Out of Hospital [At one year]

   Number of days alive and not hospitalized

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Severe symptomatic mitral regurgitation (Stage D)

• High surgical risk for open mitral valve surgery

• Subject meets the anatomical eligibility criteria for available size(s)

• NYHA Class III or IV heart failure

Exclusion Criteria:

• DMR deemed by the heart team to be operable.

• Prohibitive risk, deemed too frail or listed for cardiac transplant.

• Unsuitable cardiac structure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
2	Northwestern University	Chicago	Illinois	United States	60611
3	Henry Ford Health System	Detroit	Michigan	United States	48188
4	Washington University	Saint Louis	Missouri	United States	63110
5	Columbia University Medical Center	New York	New York	United States	10032
6	University of Washington Medical Center	Seattle	Washington	United States	98195
7	ZNA Middelheim	Antwerpen		Belgium	B 2060
8	University of Alberta	Edmonton	Alberta	Canada	T6G 2B7
9	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
10	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5

Sponsors and Collaborators

• Neovasc Inc.

Investigators

• Study Chair: Anson Cheung, MD, University of British Columbia

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 17, 2015

More Information

Additional Information:

• Company website with product information

Publications

• De Backer O, Piazza N, Banai S, Lutter G, Maisano F, Herrmann HC, Franzen OW, Søndergaard L. Percutaneous transcatheter mitral valve replacement: an overview of devices in preclinical and early clinical evaluation. Circ Cardiovasc Interv. 2014 Jun;7(3):400-9. doi: 10.1161/CIRCINTERVENTIONS.114.001607. Review.
• Kappetein AP, Head SJ, Généreux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodés-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB; Valve Academic Research Consortium-2. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Thorac Cardiovasc Surg. 2013 Jan;145(1):6-23. doi: 10.1016/j.jtcvs.2012.09.002. Epub 2012 Oct 16. Review.
• Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Creager MA, Curtis LH, DeMets D, Guyton RA, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Stevenson WG, Yancy CW; American College of Cardiology; American College of Cardiology/American Heart Association; American Heart Association. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg. 2014 Jul;148(1):e1-e132. doi: 10.1016/j.jtcvs.2014.05.014. Epub 2014 May 9. Review. Erratum in: J Thorac Cardiovasc Surg. 2014 Oct 21;64(16):1763. Dosage error in article text.

• Responsible Party: Neovasc Inc.
• ClinicalTrials.gov Identifier: NCT02276547
• Other Study ID Numbers: 047-CPT-001
• First Posted: Oct 28, 2014
• Last Update Posted: Jan 18, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Neovasc Inc.: Mitral; Regurgitation; Heart valve; Transcatheter; Transapical; Functional; Degenerative; Symptomatic, severe mitral valve regurgitation, high risk for open mitral valve surgery
• Additional relevant MeSH terms: Mitral Valve Insufficiency

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	Transcatheter mitral valve replacement with the TIARA valve and transapical delivery system Mitral valve replacement: Transcatheter mitral valve replacement
Period Title: Overall Study
STARTED	27
COMPLETED	23
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Transcatheter mitral valve replacement with the TIARA valve and transapical delivery system Mitral valve replacement: Transcatheter mitral valve replacement
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.6 (12.1)
Sex: Female, Male (Count of Participants)
Female	8 29.6%
Male	19 70.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 7.4%
Asian	2 7.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	20 74.1%
More than one race	0 0%
Unknown or Not Reported	3 11.1%
Region of Enrollment (participants) [Number]
Canada	18 66.7%
Belgium	5 18.5%
United States	4 14.8%
NYHA Functional Class (participants) [Number]
NYHA Functional Class I	0 0%
NYHA Functional Class II	0 0%
NYHA Functional Class III	26 96.3%
NYHA Functional Class IV	1 3.7%
Predicted Surgical Mortality (Probability Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Probability Percentage]	7.4 (3.7)
Ejection Fraction (Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage]	39 (8.3)
Mitral Regurgitation Severity (Count of Participants)
Severe	26 96.3%
Moderate-Severe	1 3.7%
Diabetes (Count of Participants)
Count of Participants [Participants]	8 29.6%
Hypertension (Count of Participants)
Count of Participants [Participants]	22 81.5%
Chronic Lung Disease (Count of Participants)
Count of Participants [Participants]	10 37%
Peripheral Vascular Disease (Count of Participants)
Count of Participants [Participants]	6 22.2%
Renal Dysfunction (Count of Participants)
Count of Participants [Participants]	14 51.9%
Obstructive Coronary Artery Disease (Count of Participants)
Count of Participants [Participants]	18 66.7%
Previous Coronary Artery Bypass (Count of Participants)
Count of Participants [Participants]	9 33.3%
Previous Percutaneous Coronary Intervention (Count of Participants)
Count of Participants [Participants]	11 40.7%
Previous Valve Replacement or Repair (Count of Participants)
Count of Participants [Participants]	7 25.9%
Heart Failure (Count of Participants)
Count of Participants [Participants]	27 100%
Previous Myocardial Infarction (Count of Participants)
Count of Participants [Participants]	12 44.4%
Cardiomyopathy (Count of Participants)
Count of Participants [Participants]	16 59.3%
Previous Clinically Significant Arrhythmia (Count of Participants)
Count of Participants [Participants]	23 85.2%
Prior Pacemaker/ICD/CRT (Count of Participants)
Count of Participants [Participants]	15 55.6%

Outcome Measures

1. Primary Outcome

Title	Freedom From All-cause Mortality and Major Adverse Events
Description	Defined as disabling stroke, myocardial infarction, renal failure requiring dialysis, life-threatening bleeding, and cardiac surgical or transcatheter reintervention
Time Frame	From the time of implant procedure to 30 days or hospital discharge (whichever is later)

Outcome Measure Data

Analysis Population Description

Analysis population is all participants implanted with the Tiara valve.

Arm/Group Title	Treatment
Arm/Group Description	Transcatheter mitral valve replacement with the TIARA valve and transapical delivery system Mitral valve replacement: Transcatheter mitral valve replacement
Measure Participants	27
Count of Participants [Participants]	19 70.4%

2. Secondary Outcome

Title	Number and Percentage of Subjects With All-cause Mortality, Disabling Stroke, Myocardial Infarction, Renal Failure Requiring Dialysis, Life-threatening Bleeding and Cardiac Surgical or Transcatheter Reintervention
Time Frame	30 days, 90 days, 180 days and annually to five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Individual 30 Day Rates of Device and Procedure Related Major Adverse Events
Description	All mortality All stroke Residual MR > mild (1+) Life threatening bleeding Acute kidney injury Grade 3 New pacemaker/LBBB Coronary occlusion/myocardial infarction Urgent/emergent surgery or reintervention
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number and Percentage of Subjects With Progression of Heart Failure
Description	Readmission for Heart Failure Need for Heart Failure device implantation Cardiac transplantation Listing for transplantation
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Device Success; Delivery and Deployment of the Device in the Correct Position and Retrieval of Delivery Catheter
Description	Mitral regurgitation < moderate (2+) Effective valve orifice area ≥ 1.5 cm2 as assessed by post-procedural echocardiogram Mitral Valve gradient < 5 mmHg No migration No fracture No endocarditis Stroke free No additional valve/access related interventional or surgical procedures
Time Frame	Post procedure, discharge, 30 days, 90 days, 180 days and annually for five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Performance
Description	Clinical performance as measured by NYHA Functional Class, 6MWT, and the KCCQ Hemodynamic performance as assessed by echocardiography: mean MV gradient, mitral regurgitation, effective orifice area of the MV, LV systolic and diastolic dimensions as well as volume Stroke free survival Original intended device in place No additional valve/access-related interventional or surgical procedures
Time Frame	30 days, 90 days, 180 days and annually for five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Days Alive and Out of Hospital
Description	Number of days alive and not hospitalized
Time Frame	At one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	30 days
Arm/Group Title	Treatment
Arm/Group Description	Transcatheter mitral valve replacement with the TIARA valve and transapical delivery system Mitral valve replacement: Transcatheter mitral valve replacement
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	19/27 (70.4%)
Blood and lymphatic system disorders
Bleeding	3/27 (11.1%)	3
Thrombocytopenia	1/27 (3.7%)	1
Cardiac disorders
Myocardial Infarction	2/27 (7.4%)	2
Arrhythmia and Conduction System Disturbances	2/27 (7.4%)	2
Progression of Heart Failure	10/27 (37%)	11
Decreased Ejection Fraction	1/27 (3.7%)	1
Mitral Regurgitation	1/27 (3.7%)	1
Valve Migration	2/27 (7.4%)	2
General disorders
Multi System Organ Failure	1/27 (3.7%)	1
Infections and infestations
Infection - Not related to Study Device/Procedure	5/27 (18.5%)	6
Nervous system disorders
Stroke/TIA	2/27 (7.4%)	2
Renal and urinary disorders
Acute Kidney Injury	8/27 (29.6%)	8
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/27 (3.7%)	1
Vascular disorders
Vascular Access Site and Access Related Complications	2/27 (7.4%)	2
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	6/27 (22.2%)
Cardiac disorders
Myocardial Infarction	1/27 (3.7%)	1
Eye disorders
Eye Infection	1/27 (3.7%)	1
Gastrointestinal disorders
Constipation	1/27 (3.7%)	1
Nervous system disorders
Pre Syncope	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/27 (7.4%)	2
Atelectasis	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.