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

April 19, 2010
March 7, 2012
October 2009
December 2010   (final data collection date for primary outcome measure)
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.
Return to baseline platelet function assessed by Accumetrics VerifyNow™ (VN) P2Y12 reaction units (PRU) and described by Kaplan Meier curves following a single Loading Dose (LD) of either 30 mg or 60 mg of prasugrel. [ Time Frame: 3, 5, 7, 9, and 11 days ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01107899 on ClinicalTrials.gov Archive Site
  • 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.
  • Return to baseline platelet function assessed by VerifyNow™ (VN) P2Y12 reaction units (PRU) and described by Kaplan Meier curves following a single 600-mg LD of clopidogrel. [ Time Frame: 3, 5, 7, 9 and 11 days ] [ Designated as safety issue: Yes ]
  • Describe the day to 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 ]
  • Describe the day when the proportion of subjects who return to baseline platelet function in the 30-mg and 60-mg prasugrel groups is similar to the 600-mg clopidogrel group [ Time Frame: 5 days and 7 days ] [ Designated as safety issue: Yes ]
  • Estimate the days to the return of baseline platelet function following one LD of prasugrel (30 mg or 60 mg) or 600 mg LD of clopidogrel assessed by VN-PRU [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Assess the extent of initial inhibition of platelet aggregation to the return of baseline platelet function in all treatment arms as measured by VerifyNow Platelet Reactivity Units (VN-PRU) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Compare the 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 ]
  • Compare platelet function by VN-PRU in all 3 treatment arms [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
  • Compare the proportion of poor pharmacodynamic responders in all 3 treatment arms assessed by VN-PRU greater than 230 [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
  • Assess the extent of initial inhibition of platelet aggregation to the return of baseline platelet function in all treatment arms as measured by Light Transmission Aggregometry (LTA) at 5 and 20 μM adenosine diphosphate (ADP) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Assess the extent of initial inhibition of platelet aggregation to the return of baseline platelet function in all treatment arms as measured by Multiplate® ADP test and ADP test High Sensitivity (HS) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Compare the number of days to the return of baseline platelet function in all treatment arms (adjusted for level of inhibition 24 hrs post-LD) by LTA (5 and 20 μM ADP) [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Compare the 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 HS [ Time Frame: Up through 11 days ] [ Designated as safety issue: Yes ]
  • Compare platelet function by LTA at 5 and 20 μM adenosine diphosphate (ADP) in all 3 treatment arms [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
  • Compare platelet function by Multiplate® ADP test and ADP test HS in all 3 treatment arms [ Time Frame: 24 hours post-loading dose ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study to Learn When Platelets Return to Normal After One Loading Dose of Anti-platelet Drugs in Patients With Symptoms of Acute Coronary Syndromes
Recovery of Platelet Function After a Loading Dose of Prasugrel or Clopidogrel in Aspirin-Treated Subjects Presenting With Symptoms of Acute Coronary Syndromes

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Coronary Syndromes
  • Drug: clopidogrel
    taken orally, day one, single dose
  • Drug: prasugrel
    taken orally, day one, single dose
    Other Names:
    • Efient®
    • Effient®
    • LY640315
    • CS747
  • Active Comparator: clopidogrel 600 mg
    Intervention: Drug: clopidogrel
  • Active Comparator: prasugrel 60 mg
    Intervention: Drug: prasugrel
  • Experimental: prasugrel 30 mg
    Intervention: Drug: prasugrel
Bernlochner I, Morath T, Brown PB, Zhou C, Baker BA, Gupta N, Jakubowski JA, Winters KJ, Schömig A, Kastrati A, Sibbing D. A prospective randomized trial comparing the recovery of platelet function after loading dose administration of prasugrel or clopidogrel. Platelets. 2013;24(1):15-25. doi: 10.3109/09537104.2011.654003. Epub 2012 Feb 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
29
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01107899
11983, H7T-MC-TACM
No
Eli Lilly and Company
Eli Lilly and Company
Daiichi Sankyo Co., Ltd.
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
Eli Lilly and Company
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP