1. Experience as a DES PI in Japan-USA efforts: How it has changed?
Shigeru SAITO, MD, FACC
Kamakura, JAPAN

2. Shigeru Saito, MD
I have no real or apparent conflicts of interest to report.

3. Steps forward for good clinical research in ShonanKamakura General Hospital
Apr 1998
SOP version 1
Nov 1999
IRBSOP version 1
Dec 2002
IRB revised
Independent office defined
CRC defined
Jan 2004
SOP and IRBSOP revised
Mar 2004
MHLW/FDA/Duke team visit
HBD panel discussion during JCS
Oct 2004
HBD panel discussion during CCT

4. It was in the year of 2004.
The regulatory system for device approval was completely changing to present-day system in Japan.
Industrial companies were struggling to find out the investigators, who could work hard as partners, understand new system well, and change their own style according to the new system.

5. It was in the year of 2004.
I guess the Regulatory Authority was also struggling to find how the new system could be implanted in Japanese clinical environment.
Some of physicians, including I, were also struggling how to implant the new system in their own hospitals.

6. It was in the year of 2004.
Among many industrial companies, both Medtronic and Guidant/Abbott were planning to conduct clinical trials (Chiken) in Japan for their new DES (Endeavor and SPIRIT, respectively).
However, the situation was different in those companies;
Endeavor program had been already completed, although SPIRIT program was before starting.

7. It was in the year of 2004.
Guidant/Abbott and I were discussing how to find adequate investigators for new system in order to complete SPIRIT program in Japan.
The solution was to run a “test” clinical trial program.

8. RAPID (Role of Adjunctive Post Dilatation Under IVUS Guidance for Optimal Stent Deployment) Study Overview
Study Design:
Prospective, randomized, open label, multi-center study using PENTA
Study Objective:
To evaluate the impact on long-term results of performing post dilatation after stent deployment by comparing the evaluation of optimal stent deployment results based on IVUS vs. angiography.
Major Endpoints:
Primary: In-segment minimal lumen diameter (MLD) based on 6 month angiographic follow-up.
Secondary: In-segment late lumen loss assessed by IVUS follow-up at 6 months and Clinically Driven TVF at 180 days.
Patient Enrollment:
60 patients (1:1 randomization IVUS and Non-IVUS) to be enrolled at 12 sites in Japan.

9. It was in the year of 2004.
Although RAPID trial was terminated before the total enrollment, we learnt how big and what kinds of difficulties we encountered in each hospital for the conduction of clinical trials for DES.
Long-term period for IRB approval
Poor infrastructures for the conduction of clinical trials
Poor understanding of clinical trials

10. Actual conduction of clinical trials for DES as PoC of HBD:
What we have done so far?
Actual conduction of clinical trials for DES as PoC of HBD:
Endeavor – Japan Arm
SIRIT III – Japan Arm
CoStar II – Japan Arm

11. Endeavor Japan Program as the 1st Project of HBD-Poc
Started from the Meeting with Medtronic people with Dr. Sase
On January

12. A maximum of two de novo lesions
SPIRIT III 2 : 1
Total (N=1,380)
US (N=1,292)
Japan (N=88)
A maximum of two de novo lesions
Main US RCT mm
N=1,002
XIENCE™ V
N=668
TAXUS® Control
N=334
US Non-randomized 2.25 mm arm (N=105)
Non-randomized arm in Japan mm (N=88)
US Non-randomized 4.0 mm arm (N=80)
US Non-randomized 38 mm arm (N=105)

13. CoStar Japan Arm CoStar™ Stent n=900 Main IDE RCT 2.5- 3.5 mm n=1,500*: 2
Single/Multi vessel
de novo lesions
Main IDE RCT mm
n=1,500*
CoStar™ Stent
n=900
TAXUS® Control
n=600
Non-randomized arm in Japan mm (n=100**)
IDE Direct Stenting Registry mm (n=350)
IDE PK sub-study (n=50 Single25, Multi25)
(CoStar™ n=30, TAXUS ® n=20)
*1,700 Total Patients n = 1,500 Patients (expected evaluable)
** 120 Total Patients n = 100 Patients (expected evaluable)

14. What we have learnt?
There are both similarities and differences on clinical practice between Japan and US.
The superior aspects in these differences trigger the improvement in practice in the inferior side.
Not well organized clinical trial infrastructure in Japan was much improved after launching HBD program, which was led by the superior aspects in US.
Higher proportion of use of IVUS and/or high-pressure post dilatation showed better clinical outcomes in Japan than in US.

15. Experiences from Endeavor, SPIRIT and CoStar Trials as PI:
Everybody was proud of joining the PoC program of HBD.
We did know what was the most important to conduct clinical trials?:
The relationship based on the mutual trust between the physician, hospitals, patients and their family.
This relationship is only created through the daily practice.
Investigators’ enthusiasm to conduct the trial.

16. What we have achieved through the conduction of HBD activities?
Frank communication became possible between Japan-US, Academia, Authorities and Industries.
Attitude, enthusiasm and infrastructures to conduct high-level clinical trials have been improved.
Those outcomes were achieved, because the most important part of HBD activities was “doing”.

17. PREDICTION of Progression of
Coronary Artery Disease and Clinical Outcomes
Using Vascular Profiling of Shear Stress and Wall Morphology
PREDICTION TRIAL Investigator-initiated Japan-US clinical trial, which is co-organized by BMW, the Harvard Foundation and NPO International TRI Network.
Innovative International Collaboration Between Brigham & Women’s Hospital, Harvard Medical School and Japanese Cardiologists

18. PREDICTION: Cumulative Recruitment
November 26, 2009
506 Patients Enrolled
2.7 analyzable arteries/pt
The achievement of complete enrollment in the PREDICTION Trial was possible only after the participation in HBD activities.
6-10 Mo Followup Procedure
performed in 321 patients 18

19. Do not talk about the past! It is the sign that you got old!
I want to be young, so that I will talk about the future!

20. Live Demonstration of PCI connecting from Sapporo to Beijing, Fukuoka and Miyazaki through high-speed Internet: An Empirical Experiment was done on June 28, 2008.
Sapporo
Peking University, Beijing
Kyushu University
Miyazaki

21. International Network (APAN: Asian-Pacific Advanced Network)
Netherland, Czech
Kazakhstan
Jilin
Sapporo
2003.2
2004.7
Hamburg
Bordeaux
Seoul
Iwate
Rome
2005.7
Beijing
Tokyo
2004.1
2007.8
Shanghai
Yokohama
Fukuoka
2005.6
New Dehli
Rapid progress in Information Technology will promote HBD activities around the world!
California
SirGanga Ram Hospital
HongKong
Taipei
Stanford, UC Irvine
2006.7
2007.1
Hanoi
2007.1
Taichung
Hawaii
Mumbai
HaLong
Bangkok
2004.1
Tata MH
2006.6
2005.1
Manila
Philippine U
2007.1
Ho Chi Min
我々のプロジェクトに対しては、既に韓国以外のアジア諸国からの関心も高く、ハワイを始め、北京、バンコク、台北、オーストラリアのケアンズなどとも接続済みです。
また上海・シンガポールを始めいろいろなアジア地域とも具体的な話が進行中ですが、今後は国が進めるアジアブロードバンド計画とも呼応する形で、この計画を進める必要があると考えております。
Kuala Lumper
Adelaide
Cairnes
Cho Rai Hosp
2007.3
2007.1
Flinder’s Hosp
2004.7
Before 2005
Singapore
Bandung
ITB
Canberra
NUS
Auckland
After 2008
ANU
2007.3
2006.7
Brisbane
Melbourne
Sydney
Jakarta, UI
＜Asia Medical Project＞
Brazil 21

22. In Conclusion: How we changed!
Now we finished enrolling, are doing or will do so many DES trials
Endeavor Resolute
NOBORI
Platinum-SV
Endeavor Resolute SV
Xience Prime SV
DEB-ISR
DEB-SV
BVS (Bioresorbable Vascular Scaffolding)
Now we are ready to start FIM for DES in Japan!