UMIN-CTR Clinical Trial

Public title

Single center, Exploratory Safety Evaluation Study
of Transcatheter Closure of Prosthetic Paravalvular Regurgitation

Acronym

Exploratory Evaluation Study
of Transcatheter Closure of Prosthetic Paravalvular Regurgitation (STOP PARA study)

Scientific Title

Single center, Exploratory Safety Evaluation Study
of Transcatheter Closure of Prosthetic Paravalvular Regurgitation

Scientific Title:Acronym

Exploratory Evaluation Study
of Transcatheter Closure of Prosthetic Paravalvular Regurgitation (STOP PARA study)

Region

Japan

Condition

Prosthetic paravalvular regurgitation after heart valve replacement

Classification by specialty

Cardiology

Cardiovascular surgery

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Prosthetic paravalvular regurgitation indicates the condition of the regurgitation through the adjacent position of prosthetic valve without prosthetic valve failure itself. Paravalvular regurgitation occurs in 2-10% of surgical prostheses of aortic valve and 7-17% of patients of those of
mitral valve. Most of patients with paravalvular prosthetic regurgitation do not have symptoms, but 1-5% of them have symptoms of severe heart failure or haemolytic anemia, and 1-3% of patients with paravalvular leak require reoperations due to symptomatic paravalvular leak. Conservative treatment for the clinically-severe regurgitation results in 10-year survival rates of about 30%. For those patients, the treatment of paravalvular prosthetic regurgitation traditionally has been repeat open surgery, which may be challenging because of technical factors and can be associated with high
operative risk and variable results. Actually, the mortality of repeated open surgery for paravalvular regurgitation is as high as 6-42% (13%, 15% and 37% after the first, second and third or subsequent
reoperation, respectively). Additionally, the incidence of stroke during the perioperative period, wound infection on sternotomy, infective endocarditis, and re-paravalvular regurtitation are 5.1%,
25%, 7.5%, and 20-37%, respectively. Overall, 10-year survival rates after the repeated open surgery are 63%.
Recently, percutaneous approaches to treatment of paravalvular prosthetic regurgitation have been developed and can be performed with a relatively high rate of procedural success and an acceptable incidence of complications. Overall,the 30-day complication rate was 8.7%
This study seeks to evaluate the safety of transcatheter closure of prosthetic paravalvular regurgitation for patients with heart failure and/or hemolytic anemia caused by prosthetic paravalvular regurgitation after heart valve replacement in a hospital specializing in heart diseases in Japan.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Primary outcomes

1. Major complication and failure during the procedure
Death, stroke, myocardial infarction, cardiac perforation, cardiac tamponade, cardiogenic shock, prosthetic valve failure, major bleeding, injury of great vessels caused by the procedure, embolism of organs, and embolism and/or malposition of the device.
2. Success rate and efficacy of the procedure
Acute procedural success was defined as successful deployment of one and more occluder devices that resulted in significant reduction in paravalvular regurgitation to mild or less-residual
regurgitation.

Key secondary outcomes

1. Assessment of the effectiveness
The effectiveness of the procedure is evaluated by the following items, which are compared with those before the procedure:
(1) Paravalvular regurgitation evaluated by transthoracic echocardiography at day 7 and 30 after the procedure.
(2) Paravalvular regurgitation evaluated by transesophageal echocardiography at day 7 and 30 after the procedure.
(3) NYHA class at day 7 and 30 after the procedure.
(4) 6-minute walk distance at day 7 after the procedure.
(5) Left ventricular diastolic diameters at day 7 and 30 after the procedure.
(6) Left ventricular ejection fraction at day 7 and 30 after the procedure.
(7) Plasma BNP levels at day 7 and 30 after the procedure, compared with those before the procedure.
(8) Pulmonary capillary wedge pressure immdediately after the procedure.
(9) Cardiac index immdediately after the procedure.

2. Assessment of the safety
The safety of the procedure is evaluated by the following items:
(1) Overall death in 30 days after the procedure
(2) Exacerbation of heart failure in 30 days after the procedure
(3) Exacerbation of hemolytic anemia in 30 days after the procedure
(4) Major complication and failure in 30 days after the procedure, including death from any causes, stroke, myocardial infarction, acute renal failure, cardiac perforation, cardiac tamponade, cardiogenic shock, prosthetic valve failure, valve endocarditis, major bleeding, injury of great vessels caused by the procedure, embolism of organs, and embolism and/or malposition of the device.
(5) Major adverse events in 30 days after the procedure

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

The occlusion device (Amplatzer Vascular Plug II, St. Jude Medical, Inc. MN, USA) will be implanted via percutaneous approach. The size and number of the device will be scheduled using transesophageal echocardiography and CT perfomed before the procedure. Actual size and number of the device will be
finally determined during the procedure, evaluating the residual paravalvular regurgitation after the implantation of each device with transesophageal echocardiography.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

The candidates of this study are those who are not eligible to undergo elective open-chest surgery for the repair of the paravalvular leak because of the high risk of the operation, although heart failure and/or hemolytic anemia caused by the paravalvular leak are resistant to medical therapy.

Patients will be considered for percutaneous repair if the following criteria were met:
(1) Age of 20 years old and above when got informed concent.
(2) More than mild paravalvular prosthetic regurgitation.
(3) Heart failure or hemolysis anemia which are resistant to medical treatments.
(4) High surgical risk by STS scores or the consensus between a local independent cardiologist and a cardiac surgeon that conventional surgery would be associated with excessive morbidity and mortality.

Key exclusion criteria

Patients will not be considered for percutaneous repair if the following criteria were met:
(1) Patients with metal allergy
(2) Patients with allergy to contrast agent
(3) Echocardiographic evidence of intra-cardiac mass, thrombus, or vegetation
(4) Patients in shock
(5) Patients who are or are posslibly, or are lactating
(6) Patients who are participating, or going to participate in other clinical studies.
(7) Patients judged inappropriate for the study by the principal

Target sample size

5

Name of lead principal investigator

1st name	Junjiro
Middle name
Last name	Kobayashi

Organization

National Cerebral and Cardiovascular Center

Division name

Cardiovascular Surgery

Zip code

5658565

Address

5-7-1, Fujishiro-dai, Suita, Osaka, JAPAN

TEL

81-6-6833-5012

Email

hasegawa@ncvc.go.jp

Name of contact person

1st name	Takuya
Middle name
Last name	Hasegawa

Organization

National Cerebral and Cardiovascular Center

Division name

Cardiovascular Medicine

Zip code

5658565

Address

5-7-1, Fujishiro-dai, Suita, Osaka, JAPAN

TEL

81-6-6833-5012

Homepage URL

Email

hasegawa@ncvc.go.jp

Institute

National Cerebral and Cardiovascular Center

Institute

Department

Personal name

Organization

National Cerebral and Cardiovascular Center

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

National Cerebral and Cardiovascular Center

Address

5-7-1, Fujishiro-dai, Suita, Osaka JAPAN

Tel

06-6833-5012

Email

plandiv@ml.ncvc.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2016

Year

03

Month

11

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

4

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

02

Month

26

Day

Date of IRB

2016

Year

02

Month

26

Day

Anticipated trial start date

2016

Year

02

Month

27

Day

Last follow-up date

2018

Year

12

Month

08

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2018

Year

12

Month

08

Day

Other related information

Registered date

2016

Year

03

Month

10

Day

Last modified on

2019

Year

03

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024400