SAFE STEMI for Seniors: a PASSION proof of concept study

Predictable And SuStainable Implementation Of National CardioVascular Registries Thinktank(PASSION CV Registries Thinktank)

SAFE STEMI for Seniors: a PASSION proof of concept study

Predictable And SuStainable Implementation Of National CardioVascular Registries Thinktank(PASSION CV Registries Thinktank)

October 15, 2014October 15, 2014

Proof of Concept vs. Leap of Faith?

Proof of Concept vs. Leap of Faith?

NCRI Data InfrastructureNCRI Data Infrastructure

Internal Randomization Integrated EMR->NCDR->EDC data EDC data collection for supplemental research

data (e.g. study drug admin, efficacy details) Consistent application of data validation rules Data output using CDISC SDTM 21CFR11 Compliant

NCRI WorkflowNCRI Workflow

Data Standards HarmonizationData Standards Harmonization

Initial Proof of ConceptInitial Proof of Concept

Randomized open-label trial of women undergoing PCI Hypothesis: Compared with femoral, the radial approach is:

Superior with respect to bleeding and vascular complications Non-inferior with respect to procedural failure

Protocol standardized “Best” background medical therapy to minimize bleeding risk and ischemic complications

Bivalirudin Prasugrel for ACS patients < 75 years old, no prior stroke, body

weight > 60 kg; clopidogrel otherwise GP IIb/IIIa inhibitors at operators’ discretion, intention specified

prior to randomization Arteriotomy management

Patent hemostasis mandated for radial patients Femoral closure devices allowed at operator discretion

Randomized open-label trial of women undergoing PCI Hypothesis: Compared with femoral, the radial approach is:

Superior with respect to bleeding and vascular complications Non-inferior with respect to procedural failure

Protocol standardized “Best” background medical therapy to minimize bleeding risk and ischemic complications

Bivalirudin Prasugrel for ACS patients < 75 years old, no prior stroke, body

weight > 60 kg; clopidogrel otherwise GP IIb/IIIa inhibitors at operators’ discretion, intention specified

prior to randomization Arteriotomy management

Patent hemostasis mandated for radial patients Femoral closure devices allowed at operator discretion

Initial Proof-of-Concept: TREATT / SAFE-PCIInitial Proof-of-Concept: TREATT / SAFE-PCI

SAFE-PCI Study designSAFE-PCI Study design

Female patient undergoing PCI or cardiac cath w/poss. PCI

Best background medical therapyBivalirudin, P2Y12 inhibitors

2b3a at investigator’s discretion

N=3000 pts randomized for 1800 PCI ptsPatent hemostasis required

Vascular closure devices allowed

Primary Efficacy Endpoint (72 hrs or hospital discharge):

BARC Types 2, 3, or 5 bleeding or Vascular Complications requiring intervention

Primary Feasibility Endpoint: Access site crossover

Secondary endpoints: Procedure duration, total radiation dose, total contrast volume, 30-day death/vascular complications/unplanned revascularization

Radial Femoral

NCRI and TREATT / SAFE-PCINCRI and TREATT / SAFE-PCI

As the first registry-based randomized trial in the US, the SAFE-PCI for Women trial demonstrated a new paradigm for conducting efficient pragmatic clinical trials using a National Cardiovascular Research Infrastructure

1787 women randomized at 60 US sites 96.7% of sites enrolled ≥ 1 subject 70.9% of sites enrolled ≥ 10 subjects

High quality data; Adjudication possible

CFR Part 11 compliant – IND and IDE applications

Faster enrollment, Reduced site workload by ~ 30%

Reduced costs (total budget ~ $5 million)

As the first registry-based randomized trial in the US, the SAFE-PCI for Women trial demonstrated a new paradigm for conducting efficient pragmatic clinical trials using a National Cardiovascular Research Infrastructure

1787 women randomized at 60 US sites 96.7% of sites enrolled ≥ 1 subject 70.9% of sites enrolled ≥ 10 subjects

High quality data; Adjudication possible

CFR Part 11 compliant – IND and IDE applications

Faster enrollment, Reduced site workload by ~ 30%

Reduced costs (total budget ~ $5 million)

Proof of ConceptProof of Concept

Study of Access site For Enhancing PCI in STEMI for Seniors(SAFE-STEMI for Seniors)

Study of Access site For Enhancing PCI in STEMI for Seniors(SAFE-STEMI for Seniors)

Next stage in proofs-of-concept

Public health focus: Senior population (both genders, age >= 65 years)

NCDR registry prospectively linked with claims data for long term (1-year) follow up

Randomization with factorial design radial vs. femoral access Single IRA only vs. IFR guided multivessel

intervention

Next stage in proofs-of-concept

Public health focus: Senior population (both genders, age >= 65 years)

NCDR registry prospectively linked with claims data for long term (1-year) follow up

Randomization with factorial design radial vs. femoral access Single IRA only vs. IFR guided multivessel

intervention

SAFE-STEMI for SeniorsSAFE-STEMI for Seniors

Data to evaluate therapeutic strategy and support two independent IDEs

Hypotheses: Superior bleeding and clinical outcome (NACE) at 1

year associated with radial vs. femoral vascular access

Superior death, re-MI & refractory angina associated with iFR guided multi-vessel PCI vs. IRA-only

1 year MACE performance goal for second generation DES

Data to evaluate therapeutic strategy and support two independent IDEs

Hypotheses: Superior bleeding and clinical outcome (NACE) at 1

year associated with radial vs. femoral vascular access

Superior death, re-MI & refractory angina associated with iFR guided multi-vessel PCI vs. IRA-only

1 year MACE performance goal for second generation DES

SAFE-STEMI for SeniorsStudy Design (n=~1650)SAFE-STEMI for SeniorsStudy Design (n=~1650)

Key ChallengesKey Challenges

Data Specifications Atomic definitions Timing Qualifiers Observed vs explicit

response

Parallel Workflows Patient Care Clinical Research QI Registry

Systems Interfaces More interfaces Validation purpose

Data Specifications Atomic definitions Timing Qualifiers Observed vs explicit

response

Parallel Workflows Patient Care Clinical Research QI Registry

Systems Interfaces More interfaces Validation purpose

Opportunity: ReusabilityOpportunity: Reusability

Beyond the horizonBeyond the horizon

Reusable infrastructure may facilitate opportunities for informative registry-based studies and simultaneous evaluation of treatment strategies

Consistent data standards and workflows create downstream efficiencies for future investigations

Integration with EHR initiatives will evaporate the distinction between source documents and CRFs

Reusable infrastructure may facilitate opportunities for informative registry-based studies and simultaneous evaluation of treatment strategies

Consistent data standards and workflows create downstream efficiencies for future investigations

Integration with EHR initiatives will evaporate the distinction between source documents and CRFs