PERIGON Japan Trial

A Multi-center, Non-randomized Trial to Determine the Safety and Effectiveness of the 17mm MDT-2215 Aortic Valve Bioprosthesis in Patients With Aortic Valve Disease

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02686814

Enrollment

Registered

2016-02-22

Start date

2016-03-31

Completion date

2022-07-15

Last updated

2024-04-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aortic Stenosis

Keywords

Valvular heart disease, Severe aortic stenosis, Aortic valve replacement

Brief summary

The purpose of this study is to evaluate the safety and effectiveness of the 17mm MDT-2215 aortic valve bioprosthesis.

Detailed description

This is a prospective, interventional, non-randomized, multi-center trial, with each site following a common protocol in Japan. A maximum of 20 subjects will be implanted at a maximum of 10 sites in Japan. The trial will include male and female patients of legal age to provide informed consent in Japan, requiring replacement for a diseased, damaged, or malfunctioning native or prosthetic aortic valve. Patients will be followed and assessed after implant for up to 5 years. This clinical trial information was submitted voluntarily under the applicable law and therefore, certain submission deadlines may not apply. (that is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CRF 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act of 42 CRF 11.24 and 11.44.)

Interventions

DEVICE17mm MDT-2215 aortic valve bioprosthesis

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion criteria

1. Patient has severe aortic stenosis or regurgitation, and there is clinical indication for replacement of their native or prosthetic aortic valve with a bioprosthesis, with or without concomitant procedures, which are limited to any of the following: * Left atrial appendage (LAA) ligation * Coronary artery bypass graft (CABG) * Patent foramen ovale (PFO) closure * Ascending aortic aneurysm or dissection repair not requiring circulatory arrest * Resection of a sub-aortic membrane not requiring myectomy 2. Patient is geographically stable and willing to return to the implanting site for all follow-up visits 3. Patient is of legal age to provide informed consent 4. Patient has been adequately informed of risks and requirements of the trial and is willing and able to provide informed consent for participation in the clinical trial 5. In the opinion of the investigator, pre-operative imaging indicates the patient may be suitable for a 17mm size valve

Exclusion criteria

1. Patient has a pre-existing prosthetic valve or annuloplasty device in another position or requires replacement or repair of the mitral, pulmonary or tricuspid valve 2. Patient has had previous implant and then explant of the MDT-2215 aortic valve bioprosthesis 3. Patient presents with active endocarditis, active myocarditis or other systemic infection 4. Patient has an anatomical abnormality which would increase surgical risk of morbidity or mortality, including: * Ascending aortic aneurysm or dissection repair requiring circulatory arrest * Acute type A aortic dissection * Ventricular aneurysm * Porcelain aorta * Hostile mediastinum * Hypertrophic obstructive cardiomyopathy (HOCM) * Documented pulmonary hypertension (systolic \>60mmHg) 5. Patient has a non-cardiac major or progressive disease, with a life expectancy of less than 2 years. These conditions include, but are not limited to: * Child-Pugh Class C liver disease * Terminal cancer * End-stage lung disease 6. Patient has renal failure, defined as dialysis therapy or glomerular filtration rate (GFR)\<30 mL/min/1.73 m2 7. Patient has hyperparathyroidism 8. Patient is participating in another investigational device or drug trial or observational competitive study 9. Patient is pregnant, lactating or planning to become pregnant 10. Patient has a documented history of substance (drug or alcohol) abuse 11. Patient has greater than mild mitral valve regurgitation or greater than mild tricuspid valve regurgitation as assessed by echocardiography 12. Patient has systolic ejection fraction (EF)\<20% as assessed by echocardiography 13. Patient has grade IV diastolic dysfunction 14. Patient has documented bleeding diatheses 15. Patient has had an acute preoperative neurological deficit or myocardial infarction and has not returned to baseline or stabilized ≥30 days prior to enrollment 16. Patient requires emergency surgery 17. Patient is in NYHA Class I 18. Operative

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Changes in NYHA Classification From Baseline to 1 Year Post-procedure	This outcome will be identified from measurement at baseline and 1 year.	Change in New York Heart Association (NYHA) functional classification from baseline to 1 year post-procedure will be evaluated. Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.
Effective Orifice Area Index at Baseline and 1 Year Post-procedure	This outcome will be measured at 1 year.	Effective Orifice Area Index (EOAI) at 1 year post-procedure will be evaluated. Effective Orifice Area Index (EOAI) in cm\^2/m\^2 EOAI = EOA/BSA Where: EOA is the effective orifice area in cm\^2, and BSA is the body surface area in m\^2
Number of Participants With Composite New York Heart Association (NYHA) Classification and Effective Orifice EOAI Endpoint Improvement From Baseline to 1 Year	This outcome will be identified from measurement at baseline and 1 year.	Composite number of participants with NYHA change from baseline to 1 year post-procedure of 1 or greater and effective number of participants with effective EOAI 0.6cm\^2/m\^2 or greater at 1 year post implant will be evaluated. The objective is met if at least 60% of the subjects achieve the specified improvement in NYHA and EOAI. See Objective 1 for NYHA definition See Objective 2 for EOAI definition

Secondary

Measure	Time frame	Description
Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	This outcome will be evaluated at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	NYHA functional classification evaluation at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years. Measure Description: Cardiac Disease with Functional Classes I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.
Mean Effective Orifice Area Index (cm^2/m^2) From Baseline up to 5 Years	This outcome will be evaluated at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	Effective orifice area index at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter through 5 years as measured by effective orifice area (cm\^2) per unit body surface area (m\^2). The achievement criterion for the effective orifice area index (EOAI) is defined to be ≥0.6 cm\^2/m\^2. Effective Orifice Area Index (EOAI) in cm\^2/m\^2 EOAI = EOA/BSA Where: EOA is the effective orifice area in cm\^2, and BSA is the body surface area in m\^2
Effective Orifice Area (cm^2) From Baseline up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Peak Pressure Gradient (mmHg) From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Mean Pressure Gradient (mmHg) From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Degree of Paravalvular Regurgitation From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Degree of Transvalvular Regurgitation From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Degree of Total Valvular Regurgitation From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Performance Index (L/Min) From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Cardiac Output (L/Min) From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Cardiac Index (L/Min/m^2) From Discharge up to 5 Years	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.
Safety:Valve-related Adverse Events	This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.	The early (\<=30days post-procedure), late (\>30days post-procedure) and 1-year participant counts of the following valve-related adverse events will be evaluated: * thromboembolism * thrombosis * hemorrhage * paravalvular leak * endocarditis * hemolysis * structural valve deterioration * non-structural dysfunction * reintervention * explant * death
Quality of Life Assessment - Physical Component Summary (Physical Functioning, Role-physical, Bodily Pain, General Health, Vitality)	This outcome will be evaluated at baseline, 3-6 months, 1 year and annually thereafter up to 5 years.	SF-36 Questionnaire Physical Component Summary (physical functioning, role-physical, bodily pain, general health, vitality) at baseline, 3-6 months, 1 year and annually thereafter through 5 years, where a higher score indicates a higher physical quality of life. Physical Component Summary Scale Lowest possible score: -7.28 Highest possible score: 52.71
Quality of Life Assessment - Mental Component Summary (Social Functioning, Role-emotional, Mental Health)	This outcome will be evaluated at baseline, 3-6 months, 1 year and annually thereafter up to 5 years.	SF-36 Questionnaire Mental Component Summary (social functioning, role-emotional, mental health) at baseline, 3-6 months, 1 year and annually thereafter through 5 years, where a higher score indicates a higher quality of mental life. Lowest possible score: 31.63 Highest possible score: 66.69

Countries

Japan

Participant flow

Participants by arm

Arm	Count
MDT-2215 17mm MDT-2215 aortic valve bioprosthesis	11
Total	11

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Physician Decision	14
Overall Study	Withdrawal by Subject	4

Baseline characteristics

Characteristic	MDT-2215
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	11 Participants
Age, Categorical Between 18 and 65 years	0 Participants
Age, Continuous	77.7 years STANDARD_DEVIATION 5.2
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
New York Heart Association (NYHA) Classification Class I	0 Participants
New York Heart Association (NYHA) Classification Class II	11 Participants
New York Heart Association (NYHA) Classification Class III	0 Participants
New York Heart Association (NYHA) Classification Class IV	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	11 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment Japan	11 participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 11
other Total, other adverse events	10 / 11
serious Total, serious adverse events	2 / 11

Outcome results

Primary

Effective Orifice Area Index at Baseline and 1 Year Post-procedure

Effective Orifice Area Index (EOAI) at 1 year post-procedure will be evaluated. Effective Orifice Area Index (EOAI) in cm\^2/m\^2 EOAI = EOA/BSA Where: EOA is the effective orifice area in cm\^2, and BSA is the body surface area in m\^2

Time frame: This outcome will be measured at 1 year.

Arm	Measure	Group	Value (MEAN)	Dispersion
MDT-2215	Effective Orifice Area Index at Baseline and 1 Year Post-procedure	Baseline	0.44 cm^2/m^2	Standard Deviation 0.14
MDT-2215	Effective Orifice Area Index at Baseline and 1 Year Post-procedure	1 Year	0.82 cm^2/m^2	Standard Deviation 0.17

Primary

Number of Participants With Changes in NYHA Classification From Baseline to 1 Year Post-procedure

Change in New York Heart Association (NYHA) functional classification from baseline to 1 year post-procedure will be evaluated. Measure Description: Cardiac Disease with Functional Classes (lower value is more desirable than higher value) I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.

Time frame: This outcome will be identified from measurement at baseline and 1 year.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
MDT-2215	Number of Participants With Changes in NYHA Classification From Baseline to 1 Year Post-procedure	Improved 1 Class	10 Participants
MDT-2215	Number of Participants With Changes in NYHA Classification From Baseline to 1 Year Post-procedure	No Change	1 Participants

Primary

Number of Participants With Composite New York Heart Association (NYHA) Classification and Effective Orifice EOAI Endpoint Improvement From Baseline to 1 Year

Composite number of participants with NYHA change from baseline to 1 year post-procedure of 1 or greater and effective number of participants with effective EOAI 0.6cm\^2/m\^2 or greater at 1 year post implant will be evaluated. The objective is met if at least 60% of the subjects achieve the specified improvement in NYHA and EOAI. See Objective 1 for NYHA definition See Objective 2 for EOAI definition

Time frame: This outcome will be identified from measurement at baseline and 1 year.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
MDT-2215	Number of Participants With Composite New York Heart Association (NYHA) Classification and Effective Orifice EOAI Endpoint Improvement From Baseline to 1 Year	9 Participants

Secondary

Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years

NYHA functional classification evaluation at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years. Measure Description: Cardiac Disease with Functional Classes I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. II - Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. III - Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. IV - Symptoms of heart failure at rest. Any physical activity causes further discomfort.

Time frame: This outcome will be evaluated at baseline, discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.

Population: Subjects excited prior to visit. Year 2: 1 subject (death) Year 4: 1 subject (withdraw/other) Year 5: 3 subjects (withdraw/other)

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	NYHA Classification I	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	NYHA Classification II	11 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Baseline	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	NYHA Classification I	11 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	NYHA Classification II	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	Discharge up to 30 days	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	NYHA Classification I	10 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	NYHA Classification II	1 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3-6 Months	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	NYHA Classification I	10 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	NYHA Classification II	1 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	1 Year	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	NYHA Classification I	7 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	NYHA Classification II	3 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	2 Year	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	NYHA Classification I	8 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	NYHA Classification II	2 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	3 Year	Not done	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	NYHA Classification I	6 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	NYHA Classification II	2 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	4 Year	Not done	1 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	NYHA Classification I	6 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	NYHA Classification II	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	NYHA Classification III	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	NYHA Classification IV	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	NYHA Classification V	0 Participants
MDT-2215	Assessment of NYHA Functional Classification for Participants From Baseline up to 5 Years	5 Year	Not done	0 Participants

Secondary

Cardiac Index (L/Min/m^2) From Discharge up to 5 Years

This will be measured by transthoracic echocardiography technique and will be assessed by an independent core laboratory.

Time frame: This outcome will be evaluated at discharge up to 30 days, 3-6 months, 1 year and annually thereafter up to 5 years.