Study to Learn When Platelets Return to Normal After One Loading Dose of Anti-platelet Drugs in Patients With Symptoms of Acute Coronary Syndromes

This study has been terminated.
(Terminated due to Enrollment futility)
Sponsor:
Collaborator:
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01107899
First received: April 19, 2010
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

To investigate how platelets recover to normal function in subjects who have symptoms of a heart attack or unstable angina and who get a loading dose of prasugrel or clopidogrel for planned coronary angiography.


Condition Intervention Phase
Acute Coronary Syndromes
Drug: clopidogrel
Drug: prasugrel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recovery of Platelet Function After a Loading Dose of Prasugrel or Clopidogrel in Aspirin-Treated Subjects Presenting With Symptoms of Acute Coronary Syndromes

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of Participants Returning to Baseline Platelet Function [ Time Frame: Days 3, 5, 7, 9, and 11 ] [ Designated as safety issue: Yes ]
    Participants were classified as having platelet function return to baseline after loading dose (LD) on the first day that P2Y12 Reaction Units (PRU) was no more than 60 PRU below baseline and remained in this range. PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation.


Secondary Outcome Measures:
  • The Day on Which 50%, 75% and 90% of Subjects Return to Baseline Platelet Function Following a Single LD of 30-mg or 60-mg Prasugrel or 600-mg Clopidogrel [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    This outcome measure was not analyzed due to the limited sample size.

  • The Day When the Proportion of Participants Who Return to Baseline Platelet Function in the 30-mg and 60-mg Prasugrel Groups is Similar to the 600-mg Clopidogrel Group at Day 5 and Day 7 [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    The day at which the proportion of participants who return to baseline platelet P2Y12 receptor function in the prasugrel 30 mg and 60 mg LD groups is similar (within 10% absolute difference) to the proportion of subjects who return to baseline platelet P2Y12 receptor function at day 5 and day 7 in the clopidogrel 600 mg LD group, obtained from Kaplan Meier curves for the primary washout population, was to be presented. This outcome measure was not analyzed due to the limited sample size.

  • Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    The return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by Verify Now™ P2Y12 Reaction Units (VN-PRU). This outcome measure was not analyzed because it was not appropriate to estimate the days based on the non-inferiority approach due to the limited sample size.

  • Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    To show effect of initial inhibition of platelet aggregation as measured by Accumetrics Verify Now™ P2Y12 on the day to return to baseline platelet function, a regression model was fitted with day to return as outcome variable and initial inhibition as fixed effect. Results are reported as the predicted day to return to baseline platelet function by derived VN-PRU percent (%) inhibition at 24 hours post LD. The derived VN-PRU % inhibition is calculated as a percent decrease of PRU from baseline using the following formula: ([PRU at baseline - PRU at 24 hours post LD]/PRU at baseline) x 100%.

  • Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by VN-PRU [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of adenosine diphosphate (ADP)-stimulated platelet aggregation. This outcome measure was not analyzed due to the limited sample size.

  • Platelet Function 24 Hours Post Loading Dose [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
    PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation.

  • Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
    Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230.

  • Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 μM ADP. Maximum platelet aggregation (MPA) is reported by day.

  • Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    Return of baseline platelet function was assessed by Multiplate® ADP test and ADP test High Sensitivity (HS). Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. The agonist ADP was added to stirred whole blood after dilution (1:2 with 0.9% NaCl solution) in a final concentration of 6.4 µM (ADP Test) or in final concentration of 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADPtest HS). Platelet aggregation was continuously recorded for 5 minutes and quantified as area under the aggregation curve (AUC=AU*min) of aggregation units (AU).

  • Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hours Post-LD) by LTA (5 and 20 μM ADP) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    Maximum platelet aggregation (MPA) to 5 and 20 μM ADP were assessed by LTA. This outcome measure was not analyzed due to limited sample size.

  • Mean Number of Days to the Return of Baseline Platelet Function in All Treatment Arms (Adjusted for Level of Inhibition 24 Hrs Post-LD) by Multiplate® ADP Test and ADP Test High Sensitivity (HS) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
    The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM Prostaglandin E1 (PGE1) (ADP test HS), area under the aggregation curve (AUC) was calculated. This outcome measure was not analyzed due to limited sample size.

  • Platelet Function by LTA at 5 and 20 μM ADP [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
    MPA to 5 and 20 μM ADP were assessed by LTA.

  • Platelet Function by Multiplate® ADP Test and ADP Test HS [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
    The Multiplate analyzer was used to assess platelet aggregation based on impedance aggregometry in whole blood. After adding 6.4 µM ADP (ADP test) or 6.4 µM ADP plus 9.4 nM PGE1 (ADP test HS), area under the aggregation curve (AUC) were calculated.


Enrollment: 29
Study Start Date: October 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: clopidogrel 600 mg Drug: clopidogrel
taken orally, day one, single dose
Active Comparator: prasugrel 60 mg Drug: prasugrel
taken orally, day one, single dose
Other Names:
  • Efient®
  • Effient®
  • LY640315
  • CS747
Experimental: prasugrel 30 mg Drug: prasugrel
taken orally, day one, single dose
Other Names:
  • Efient®
  • Effient®
  • LY640315
  • CS747

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women ≥18 to <80 years of age who present with any one of the following:
  • symptoms of Acute Coronary Syndromes (ACS)
  • clinical symptoms of angina, or a positive stress test or who return for routine follow up angiography post stent placement in whom co-administration of aspirin and a thienopyridine (that is, clopidogrel, ticlopidine, or prasugrel) is not contraindicated

Exclusion Criteria:

  • Those presenting with ST-elevation MI (STEMI)
  • histories of refractory ventricular arrhythmias
  • an implanted defibrillator device
  • congestive heart failure (NYHA Class III or above) within 6 months prior to screening
  • significant hypertension
  • subjects with a history or clinical suspicion of cerebral vascular malformations, transient ischaemic attack, or stroke
  • bleeding disorders
  • women known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01107899

Locations
Germany
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Munich, Germany, 80636
Sponsors and Collaborators
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01107899     History of Changes
Other Study ID Numbers: 11983, H7T-MC-TACM
Study First Received: April 19, 2010
Results First Received: December 1, 2011
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Acute Coronary Syndromes
Angina
Platelet Function
Coronary Angiography
Clinical Symptoms of Angina
Positive Stress Test

Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Disease
Pathologic Processes
Clopidogrel
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014