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

Acute Coronary Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01107899
• Other study ID #: 11983
• Secondary ID: H7T-MC-TACM
• Status: Terminated
• Phase: Phase 1
• First received: April 19, 2010
• Last updated: March 7, 2012
• Start date: October 2009
• Est. completion date: December 2010

Study information

• Verified date: March 2012
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• Syndrome

Intervention

Drug:
• clopidogrel
taken orally, day one, single dose
• prasugrel
taken orally, day one, single dose

Locations

Country	Name	City	State
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

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Returning to Baseline Platelet Function	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.	Days 3, 5, 7, 9, and 11	Yes
Secondary	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	This outcome measure was not analyzed due to the limited sample size.	Up through 11 days	Yes
Secondary	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	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.	Up through 11 days	Yes
Secondary	Number of Days to the Return of Baseline Platelet Function Following One Loading Dose (LD)	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.	Up through 11 days	Yes
Secondary	Effect of Initial Inhibition of Platelet Aggregation on the Day to Return to Baseline Platelet Function: VN-PRU	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%.	Up through 11 days	Yes
Secondary	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	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.	Up through 11 days	Yes
Secondary	Platelet Function 24 Hours Post Loading Dose	PRU was assessed by Accumetrics Verify Now™ P2Y12. PRU represents the rate and extent of ADP-stimulated platelet aggregation.	24 hours post-loading dose	Yes
Secondary	Percentage of Poor Pharmacodynamic Responders by Platelet Aggregation at 24 Hours Post-LD	Platelet aggregation was assessed by Accumetrics Verify Now™ P2Y12, and poor responders were those with PRU greater than or equal to 230.	24 hours post-loading dose	Yes
Secondary	Extent of Initial Inhibition of Platelet Aggregation on the Return of Baseline Platelet Function: Light Transmission Aggregometry (LTA)	Initial inhibition of platelet aggregation was measured by LTA at 5 and 20 µM ADP. Maximum platelet aggregation (MPA) is reported by day.	Up through 11 days	Yes
Secondary	Extent of Initial Inhibition of Platelet Aggregation to the Return of Baseline Platelet Function: Multiplate® ADP Test and ADP Test High Sensitivity (HS)	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).	Up through 11 days	Yes
Secondary	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)	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.	Up through 11 days	Yes
Secondary	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)	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.	Up through 11 days	Yes
Secondary	Platelet Function by LTA at 5 and 20 µM ADP	MPA to 5 and 20 µM ADP were assessed by LTA.	24 hours post-loading dose	Yes
Secondary	Platelet Function by Multiplate® ADP Test and ADP Test HS	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.	24 hours post-loading dose	Yes