Acute Coronary Syndromes

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Lessons from the TASTE trial
Prospective Registry based Randomized Clinical
Trials (RRCT) a new concept for clinical
research

• Stefan James, Uppsala University
• Ole Fröbert, Örebro University, Göran Olivecrona,
  Lund University, David Erlinge, Lund University,
  Tomas Jernberg, Karolinska Institute, Stockholm,
  Bertil Lindahl, Uppsala University, Lars
  Wallenting, Uppsala University, Bo Lagerqvist,
  Uppsala University

Sweden
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Weaknesses
Randomized Clinical Trials- RCT
Strengths

• Correctly designed studies with adequate power
  are gold standard
• Extinguishes confounding

• Expensive
• Highly selected populations due to exclusion
  criteria
• Often selected specialized study centers
• Often surrogate endpoints
• Long time to plan and complete
• Often sponsored by industry- only studies with
  economic interest will be performed

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Thrombus aspirationin Sweden
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TAPAS
Vlaar, P.J. et al. The Lancet 2008 3711915-20
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• Number of cases annually 80 000
• RIKS-HIA 73 CCU hospitals, 100
• SCAAR 30 PCI hospitals, 100
• Percutaneous valves 7 hospitals, 100
• Heart surgery 7 hospitals, 100
• Secondary prevention 65 hospitals, 85
• gt150 variables
• (Baseline data, procedural and outcome
  measures)
• At monitoring 95-96 agreement between files and
  registry.

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Registry based Randomized Trial
Personal data
Data entry on line by the operator
Automatic linkage with population registry
Clinical background and prior CV disease
Automated data checks
Angiographic background data
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Two questions need to be answered Did the
patient consent orally? Are inclusion and no
exclusion criteria met?
Did the patient consent?
Are inclusion and exclusion crieteria met?
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Information for consent
Did the patient consent?
Are inclusion and exclusion crieteria met?
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TASTE inclusion rate
Patients
All primary PCIs
Randomized
7244 patients
Date
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TASTE trial enrollment flow chart
All patients with STEMI in Sweden and Iceland
undergoing primary or rescue PCI. N11 709 )
Enrolled in Denmark N247
Enrolled in TASTE N7259
Not enrolled N4697
Erroneous enrollments N15
Randomized in TASTE N7244
No patients (0) were lost to follow-up of the
primary outcome!
N3621 assigned to thrombus aspiration
N3623 assigned to conventional PCI
N3399 underwent thrombus aspiration N222
underwent conventional PCI
N3535 underwent conventional PCI
N1162 underwent thrombus aspiration
N3445 underwent conventional PCI N178
underwent thrombus aspiration
N3621 were followed up
N3623 were followed up
N1162 were followed up
N3535 were followed up
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Ongoing and planned R-RCTs
DETOX-AMI DETermination of the role of OXygen in
Acute Myocardial Infarction, N7000 VALIDATE
Bivalirudin versus Heparin in NST and ST-
Elevation myocardial infarction in patients on
modern antiplatelet therapy in SWEDEHEART,
N6000 SWEDEPADSWEdish Drug Elution trial in
Peripheral Arterial Disease N2500 Prospect
II-Absorb To test if the progress of non-flow
obstructing lesions with a plaque burden gt70 is
reduced by treatment with Absorb Bioresorbable
Vascular Scaffold (BVS) as compared to optimal
medical therapy (OMT) N300
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R-RCT vs. classical RCT

• New concept for clinical research
• Combines the advantages of a clinical registry
  and randomized study
• Complement to classical RCT No substitute

• RRCT
• Evaluation of therapeutic options available/used
  in routine clinical care

RCT Approval of new pharmaceutical agents and
medical devices
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RRCT Registry based Randomized Clinical Trials

• Challenges
• Design simple, one main hypothesis
• Variable definitions
• Randomization on-line
• Data completeness
• Data validity
• Monitoring- limited
• Primary outcome variable- defined and available
• Adjudication selected outcome variables
• Work load for regular clinical staff

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Conclusions

• Large need for randomized trials (RCT)
  particularly for the evaluation of strategies,
  devices, pharmacological therapies
• Classical RCTs are often not performed in broad
  representative patient populations
• National clinical registries have representative
  patient populations and networks for
  collaboration
• Prospective Registry based Randomized Clinical
  Trials (RRCT) is a new opportunity for clinical
  research
• RRCT is ideal for one clinically important
  hypothesis with reliable hard endpoints