Clinical Trial Commentary

1
Clinical Trial Commentary
ESPRIT

• Dr Eric Topol
• Chairman and Professor, Department of Cardiology
• Director of the Joseph J Jacobs Center for
  Thrombosis and Vascular Biology at the Cleveland
  Clinic
• Dr Robert Califf
• Professor of Cardiology
• Associate Vice Chancellor for
• Clinical Research at Duke University

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  clinical trials affecting cardiologists.
•  
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•  
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  editorial board.

3
ESPRIT trial

• Enhanced Suppression Of Platelet Receptor GP
  IIb-IIIa using INTEGRILIN Therapy
• GP IIb-IIIa inhibitors have repeatedly shown to
  be beneficial in percutaneous intervention
• these drugs have been used in less than half of
  all eligible patient in the past few years
• difference between small molecule GP IIb-IIIa
  inhibitors (egeptifibatide) and antibody
  inhibitors (egabciximab) was apparent
• ESPRIT trial designed after the IMPACT 2 study
  showed modest benefit with eptifibatide

4
ESPRIT trial early suspension

• COR Therapeutics Inc and Schering-Plough
  Corporation today announced they would suspend
  enrollment in the ongoing ESPRIT trial after
  interim analysis showed a significantly lower
  rate - about 50 - of death and MI among patients
  randomized to receive eptifibatide (Integrilin),
  a IIb-IIIa inhibitor, during stenting procedures
  

heartwire / February 4, 2000 / ESPRIT study
halted
5
ESPRIT trial

• Enhanced Suppression Of Platelet Receptor GP
  IIb-IIIa using INTEGRILIN Therapy
• Lead investigator
• Dr James Tcheng, Duke University
• Patients undergoing nonurgent percutaneous
  coronary intervention with stenting were
  randomized to eptifibatide or placebo.
• Eptifibatide was given as a 180 µg/kg bolus,
  followed by a 2 µg/kg/min infusion, followed 10
  minutes later by a second 180 µg/kg bolus. The
  infusion was continued for up to 24 hours.

6
ESPRIT trial

• The preliminary results of ESPRIT not only
  ratify the benefits of GP IIb-IIIa blockade,
  they do it with several exclamation marks.
• Dr Eric Topol
• Chairman and Professor
• Department of Cardiology
• Cleveland Clinic

7
ESPRIT trial

• Enhanced Suppression Of Platelet Receptor GP
  IIb-IIIa using INTEGRILIN Therapy
• Primary endpoint
• combined incidence of death, MI, urgent repeat
  intervention, need for bail-out GP IIb-IIIa
  inhibitor therapy at 48 hours
• Secondary endpoints
• composite endpoint and composite endpoint of
  death, MI, or urgent repeat revascularization at
  12 hours, 24 hours, 7 days and 30 days
• original randomization to include 2400 patients

8
ESPRIT trial

• Enhanced Suppression Of Platelet Receptor GP
  IIb-IIIa using INTEGRILIN Therapy
• n1758
• 30 day endpoint Integrilin vs placebo p
  value
• Combined incidence
• of death and MI 50 lower
  0.0011

9
ESPRIT trial

• significant results obtained for 30 day endpoint
  and as early as 48 hours after the procedure
• no excess of severe bleeding events with
  eptifibatide
• modest elevation in the rate of moderate
  bleeding, mostly femoral artery bleeding
• eptifibatide (Integrilin) costs 350-400,
  compared to abciximab (Reopro), which costs
  1350-1400

10
ESPRIT trial

• this trial is not a direct comparison of GP
  IIb-IIIa inhibitors
• 6-month and 1-year mortality data are unknown
• for unequivocal comparisons, would need a
  head-to-head randomized trial
• cost analyses should include benefit as a
  function of the length of infusion, since
  eptifibatide is a short-acting molecule

11
ESPRIT trial

• The results of this study reinforce our
  conviction that GP IIb-IIIa inhibitors should be
  the standard of care for patients undergoing
  intracoronary stenting.
• Dr Robert Califf
• Professor of Cardiology
• Associate Vice Chancellor for
• Clinical Research at Duke University

heartwire / February 4, 2000 / ESPRIT study
halted
12
ESPRIT trial

• The evidence was so strong before ESPRIT and now
  it goes to a whole other level. But its
  disenchanting at the very least to think that
  still more than half the patients arent getting
  the benefits of the therapy. So this trial has a
  phenomenal step in the right direction.
• Dr Eric Topol
• Chairman and Professor
• Department of Cardiology
• Cleveland Clinic

13
ESPRIT trial

• hospital pharmacy budgets are increasing
  substantially due to FDA approval of good drugs
  at record rates
• an avalanche of new drugs is anticipated with
  combinatorial chemistry and the human genome
  project
• choice of therapies and devices is an area where
  evidence based medicine, such as the ESPRIT
  trial, becomes increasingly important

14
EPISTENT trialmortality at 1 year
of pts, death
57 p 0.037



of Pts, Death
3.0
3.0
stent placebo, n 809
2.4
2.5
stent abciximab, n 794
2.5
balloon abciximab, n 796
2.1
2.0
2.0
1.5
1.5
1.0
1.0
1.0
0.5
0.5
0.0
0.0
0
60
120
180
240
300
360
0
60
120
180
240
300
360
Days from Randomization
Days from randomization