Study of Access Site for Enhancement of PCI for Women (SAFE-PCI for Women)

1. Study of Access site For
Enhancement of PCI for
Women (SAFE-PCI for
Women)
Sunil V. Rao MD
Duke Clinical Research Institute

2. Disclosures
 Consultant/Honoraria
 Zoll, The Medicines Company, Terumo Medical,
Daiichi Sankyo Lilly, Astra Zeneca
 Research funding
 Ikaria, Cordis
 Off-label uses of drugs or devices will not be
discussed in this presentation

3. TREATT I ThinkTank
 The rate of radial approach is lower in the US
compared with other countries
 Lack of education and perhaps lack of large US-
based randomized data may be responsible
 Large appetite for a randomized trial looking at
clinical outcomes
 Less enthusiasm for labeling changes
 Challenge is randomization
 Femoralists unable to randomize to radial
 Radialists unwilling to randomize to femoral

4. Female gender and access site complications
Ahmed B, et. al. Circulation 2009

5. Predictors of Major Femoral Bleeding
N=17,901 pts from Mayo Clinic 1994-2005
Major femoral bleeding defined as hematoma > 4 cm, external bleeding requiring surgery
or blood transfusion, or retroperitoneal hematoma
Doyle BJ, et. al. JACC:Interventions 2008

6. PCI-related outcomes in women
N=22,725 PCI pts in the BMC2 Registry
Risk of PCI outcomes Women vs. Men
Duvernoy CS, et. al. AHJ 2010

7. CATH-PCI Registry: Trend in the Use of radial PCI Over
Time in Key Subgroups
n=593,094
Radial access: 1.32%
Rao, S. V. et al. J Am Coll Cardiol Intv 2008;1:379-386

9. Transradial PCI in women
 Smaller diameter arteries
 May not accommodate 6F systems readily
 May be associated with greater degree of spasm
 Female sex independently associated with forearm
hematomas in the EASY trial
Saito S, et. al. CCI 1999
Bertrand OF, et. al. AHJ 2009

10. SAFE-PCI Equipoise
 Females at higher risk for vascular and bleeding
complications
 It may be more difficult to complete transradial
procedures in women
 Women may be at higher risk for bleeding after
transradial PCI

11. SAFE-PCI for Women Trial Structure
 Clinical and Data Coordinating Center - DCRI
 Study chair - Mitch W. Krucoff MD,
 Principal Investigator - Sunil V. Rao MD
 DCRI Project lead – Britt Barham
 Sponsors
 Terumo Medical, Abbott Vascular, The Medicines Company,
Eli Lilly others pending approval of applications
 Partners
 NCRI (David Kong, Eric Peterson, Bob Harrington), ACC, FDA
Office of Women’s Health, CSRC
 DSMB
 Spencer King (chair), Olivier Bertrand, Alexandra Lansky,
Statistician TBD

12. Objectives
 To determine the efficacy and feasibilty of the
transradial approach to PCI in women
 Secondary:
 To determine the association between transradial
PCI and procedure time, radiation dose, and
contrast volume
 To determine the association between transradial
PCI and resource use, patient preferences, and
quality of life*
 To determine the association between transradial
PCI and 30-day death, vascular complications and
repeat revascularization
*If funding can be obtained

13. Inclusion/exclusion criteria
Inclusion Exclusion
 Age > 18 years  Non-palpable radial or femoral
pulses
 Female patient undergoing  Bilateral IMA grafts
elective or urgent PCI or
 Bilateral abnormal Barbeau tests
 Undergoing diagnostic  Hemodialysis AV fistula or graft
angiography to evaluate in arm to be used for PCI
ischemic symptoms with the  INR ≥ 1.5
possibility of PCI  Planned staged PCI within 30d
of index PCI
 Have capacity to sign
informed consent  Valvular heart disease requiring
surgery
 Planned RHC
 Primary PCI for STEMI

14. Primary efficacy and feasibility endpoints
 Efficacy – BARC Types 2, 3, and 5 bleeding or major
vascular complications occurring within 72 hrs of PCI or
hospital discharge, whichever comes first
 Vascular complications defined as:
 AV fistula
 Arterial pseudoaneurysm
Requiring surgical intervention
 Arterial occlusion
 Primary feasibility endpoint
 Procedural failure – inability to complete the procedure from
the assigned access site.
 CEC adjudication of Bleeding and vascular complication
endpoints

15. Study of Access site For Enhancing PCI for
Women (SAFE-PCI for Women)*
Female patient undergoing urgent or elective PCI
Best background medical therapy
Bivalirudin, Clopidogrel, Prasugrel
2b3a at investigator’s discretion
N=1800 pts, 30 sites
Sites from NCRI
Radial Femoral
Patent hemostasis required
Vascular closure devices allowed
Primary Efficacy Endpoint: BARC Types 2, 3, or 5 bleeding or Vascular
Complications requiring surgical intervention
Primary Feasibility Endpoint: Procedural failure
Secondary endpoints: Procedure duration, total radiation dose, total contrast
volume
*Planned in collaboration with ACC, CSRC, FDA Office of Women ’s Health

16. Sample size assumptions and calculations
 Assumptions:
 Rate of primary composite endpoint in femoral arm –
8.0%
 Assume 50% reduction with radial approach
 Sample size:
 1800 patients provides >90% power at 2-sided
alpha=0.05

17. NCRI
 Case report form built on the CathPCI registry form
 60% of the crf completed
 Adding randomization to data acquisition harnesses the
NCDR backbone to create an efficient platform for large
simple randomized clinical trials.
 Site identification (> 1000 sites represented in the
registry)
 How many radials are being at each site?
 How many PCIs in women are being done at each
sites?
 How many radial PCIs are being done in women at
each site?
 21 CFR 11 compliant

18. Funding Support
 American Recovery & Reinvestment Act of 2009 (ARRA)
 NIH Research and Research Infrastructure “Grand
Opportunities” (GO) initiative
 “Substantially accelerate comparative effectiveness
research, advance methods development and priority
setting, and forge robust infrastructure to support the
conduct of comparative effectiveness research.”
 NHLBI Award 1RC2HL101512-01
 $2.6M over 2 years

19. SAFE-PCI for Women
 The first large multicenter collaborative trial
comparing radial and femoral approaches in the
modern (post-RIVAL) era
 One of the few interventional randomized trials in
women
 Opportunities and challenges to answering
important questions related to access site
approaches and bleeding risks
 Develop a template for future interventional trials