UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Safety and Efficacy of transcatheter closure of paravalvular leaks
Title of the study (Brief title)	Catheter closure of PVL
Region	Japan

Condition
Condition	symptomatic paravalvular leak after valve replacement surgery
Classification by specialty	Medicine in general Cardiology Cardiovascular surgery
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Paravalvular leak(PVL) is often observed in patients post valve replacement or valve implantation(TAVI) with a reported frequency at 2-17%. Most patients with PVLs are asymptomatic hence requiring no additional therapy, however, small portion of patients can present either with recurrent hemolytic anemia or heart failure due to paravalvular regurgitation or both. Re-do surgery has been proposed as gold standard therapy for these symptomatic PVLs. However, re-do surgery per se are often underwent with high perioperative mortality and morbidity and recurrent PVLs are frequently observed after surgery due to calcification and fragility of the tissue. Under those circumstances, transcatheter therapy for PVLs has been developed with a first successful report for consecutive four PVL cases in 1992. Afterwards a number of case report or cohort study has been published. A meta-analysis published in 2014 reports that overall procedural success rate were 76.5% . Moreover, ACC/AHA guideline about management of valvular heart disease published in 2014 endorses transcatheter therapy for PVLs to patients with high operative risk as class IIb. Most reported cases hitherto were treated with Amplatzer Vascular Plug family which are approved for occlusion of the abnormal vessels but not approved for this purpose in Japan as well as other countries. On the other hand, Occultech PLD device (Occultech, Helsingborg, Sweden) were approved for CE mark as specifically designed device for PVL closure at EU in 2014 October. Occultech PLD device has suitable structure for closing the flow across the PVLs due to PTE sheet inside the device, therefore will be considered and utilized more as a special device for this treatment. To summarize, the transcatheter therapy has been developed and underwent for over 10 years all over the world except Japan. Therefore this exploring clinical study was designed to assess safety and efficacy of transcatheter therapy using the device
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Technical success rate of deployment of the closing device in the acute settings.
Key secondary outcomes	Severe Adverse events observed during the whole study period. Improvement of hemolytic anemia (LDH, Hb, Ht, Haptoglobin, TBil, urine bil) Improvement of paravalvular regurgitation (by Echo), LV function, LV size, BNP level Improvement of NYHA class Improvement of QOL score as determined by MLHFQ

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	To deploy occlusion device( Amplatzer Vascular Plug II(IV) or Occultech PLD device) according to the size and shape of the PVLs. Anatomy and location of the PVL should be carefully reviewed to determine the access route, i.e. transfemoral-transseptal approach(femoral vein/artery puncture) or transapical approach(requiring surgical minithoracotomy)
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	Patients who meet all the following criteria at the screening period are eligible for the study: 1) More than 20 years of age 2) Presence of paravalvular leak after valve replacement 3) Life expectancy more than 1 year 4) Suitable anatomy for transcatheter closure of the PVLs 5) No coagulopathy disease 6) Presence of either or both for symptomatic(NYHA class 2 or more)heart failure due to paravalvular regurgitation post valve replacement of the mitral /aortic valve or refractory hemolytic anemia due to PVLs requiring frequent episodes of transfusion(Hb<10g/dl and LDH>600IU/l and haptoglobin<10mg/dl. or requirement of MAP transfusion or EPO administration during recent 90days to achieve Hb level >10g/dl). 7) Patients deemed as high risk or inoperable for re-do surgery 8) Patients is informed well and can understand the study protocol by the attending physician. 9) Patients give written informed consent voluntarily to attend the study.
Key exclusion criteria	Patients who, at the start of screening, meet any of the following criteria are not eligible for the study: 1) Uncorrectable coagulopathy or bleeding tendency. 2) Contraindication for emergent transfusion/antiplatelet 3) Anatomically difficult for femoral puncture 4) Severe liver dysfunction 5) Severe uncontrollable systemic or local infection 6) Known allergy or contraindication for contrast 7) Known allergy for nickel/titan/stenless steel/platinum/iridium 8) Past history of severe drug allergy 9) Patients with organic lesion with hemorrhagic risk including hemorrhagic stroke within past six months 10) Patients with possible bleeding disorder(internal malignancy, diverticulitis, colitis, subacute bacterial endocarditis, severe hypertension, uncontrolled diabetes etc) 11) Patients enrolled to other clinical study with intervention or clinical trial by medicine or device within past six months 12) Intracardiac thrombus formation 13) Patients deemed as inappropriate for participating in the study by principal investigator or subinvestigator
Target sample size	15

Research contact person
Name of lead principal investigator	Takeshi Arita
Organization	Kyushu University Hospital
Division name	Heart Center
Address	3-1-1, Maidashi,Higashi-ku, Fukuoka
TEL	092-642-5235
Email	takeshi.arita@gmail.com

Public contact
Name of contact person	Takeshi Arita
Organization	Kyushu University Hospital
Division name	Heart Center
Address	3-1-1, Maidashi, Higashi-ku, Fukuoka
TEL	092-642-5235
Homepage URL
Email	takeshi.arita@gmail.com

Sponsor
Institute	Kyushu University Hospital
Institute
Department

Funding Source
Organization	Educational donation
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

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

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	九州大学病院（福岡県）、東邦大学医療センター大橋病院（東京都）

Other administrative information
Date of disclosure of the study information	2015 Year 11 Month 10 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2015 Year 11 Month 10 Day
Anticipated trial start date	2015 Year 12 Month 25 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 11 Month 06 Day
Last modified on	2018 Year 07 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000022445