UMIN-CTR Clinical Trial

Basic information
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
Condition	Prosthetic paravalvular regurgitation after heart valve replacement
Classification by specialty	Cardiology Cardiovascular surgery
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
Last 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

Public contact
1st 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

Sponsor
Institute	National Cerebral and Cardiovascular Center
Institute
Department

Funding Source
Organization	National Cerebral and Cardiovascular Center
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
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
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 03 Month 11 Day

Related information
URL releasing protocol
Publication of results	Published

Result
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

Progress
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
Other related information

Management information
Registered date	2016 Year 03 Month 10 Day
Last modified on	2019 Year 03 Month 25 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000024400