UMIN-CTR Clinical Trial

Public title

Safety and Efficacy of transcatheter closure of paravalvular leaks

Acronym

Catheter closure of PVL

Scientific Title

Safety and Efficacy of transcatheter closure of paravalvular leaks

Scientific Title:Acronym

Catheter closure of PVL

Region

Japan

Condition

symptomatic paravalvular leak after valve replacement surgery

Classification by specialty

Medicine in general	Cardiology	Cardiovascular surgery

Classification by malignancy

Others

Genomic information

NO

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

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

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Takeshi Arita

Organization

Kyushu University Hospital

Division name

Heart Center

Zip code

Address

3-1-1, Maidashi,Higashi-ku, Fukuoka

TEL

092-642-5235

Email

takeshi.arita@gmail.com

Name of contact person

1st name
Middle name
Last name	Takeshi Arita

Organization

Kyushu University Hospital

Division name

Heart Center

Zip code

Address

3-1-1, Maidashi, Higashi-ku, Fukuoka

TEL

092-642-5235

Homepage URL

Email

takeshi.arita@gmail.com

Institute

Kyushu University Hospital

Institute

Department

Personal name

Organization

Educational donation

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2015

Year

11

Month

10

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

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

Terminated

Date of protocol fixation

2015

Year

11

Month

10

Day

Date of IRB

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

Other related information

Registered date

2015

Year

11

Month

06

Day

Last modified on

2018

Year

07

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022445