P3AMI Antiplatelet Trial

• Sponsor: The Royal Wolverhampton Hospitals NHS Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT02376283
• Collaborator: (none)
• Enrollment: 87
• Location: 1
• Arms: 6
• Actual Duration (Months): 19.8
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

Major heart attacks are caused by a numerous factors, including sudden clot formation in a coronary artery leading to a blockage and heart muscle death. The clots are largely made of sticky clotting blood cells (platelets). A patient having a major heart attack is treated with emergency primary percutaneous coronary intervention (PPCI) where a wire and balloon are used to reopen the coronary artery and a stent (a slotted metal tube) is placed to keep the artery open.

Aspirin, and one of two other antiplatelet drugs (prasugrel or ticagrelor) are given prior to PPCI to prevent further clots formation. Both antiplatelet drugs are taken in tablet form and in healthy stable patients these drugs take at least 30 min to 2 hours to exert an adequate effect. Often PPCI procedures are performed well within this timescale. It is possible that having a major heart attack limits the bodies ability to absorb the drugs also.

In this study, patients with major or minor heart attacks will be given either prasugrel or ticagrelor as per licensed indications and guideline recommendations. A 15 ml blood sample will be taken at first balloon inflation to reopen the blocked artery, then after 20 minutes, 60 minutes, and 4 hours after taking the drugs. Each blood sample will be subjected to a variety of tests to determine antiplatelet drug activity.

This study will identify which of the two agents used are working effectively during PPCI, given the very short timescales involved. It will also show if patients with major heart attacks absorb the drugs less well than patients with less severe heart attacks. In the future it might be that an intravenous agent will be more valuable in the setting of PPCI.

Condition or Disease	Intervention/Treatment	Phase
Heart Attack	Drug: Prasugrel; Drug: Clopidogrel; Drug: ticagrelor	Phase 4

Detailed Description

This is a pilot study by design, which will be nonrandomized in nature. A total of 90 subjects will be included in the study distributed equally into 6 patient groups which have been carefully selected so that all patients will receive antiplatelet drugs as per current accepted NICE (National Institute for Health and aCare Excellence) guidelines and licensed indications.

In the current ethically approved protocol ver 1.4 (5/11/12) Groups 1,3 and 4 have already been recruited to and a full data set has been collected; Group 1 STEMI (ST-segment elevation myocardial infarction) prasugrel Group 3 STEMI clopidogrel Group 4 NSTEMI (Non-ST segment elevation myocardial infarction) clopidogrel

The current protocol allows for a specific group of NSTEMI patients (diabetic <75 years of age, >60 kg) treated with prasugrel to be recruited. The restrictive nature of these criteria would not allow us to make a direct comparison to STEMI patients treated with prasugrel. In light of this the eligibility criteria has been widened for NSTEMI patients to be treated with prasugrel. The proposed NSTEMI criteria is as follows:

1. Group 2: Patients with NSTEMI who are under 75 years of age and greater than 60kg in weight receive prasugrel loading (60mg) (in line with the manufacturers recommendations and licensing) after the 4 hour sample collection period those patients who are treated with percutaneous coronary intervention will receive prasugrel at a maintenance dose of 10mg daily (in line with NICE recommendations and local guidelines), those patients who do not proceed to be treated with percutaneous coronary intervention will be switched to clopidogrel 75mg daily (in line with NICE recommendations and local guidelines) on the following day.

The investigators also propose to include recruitment of the following two groups in which ticagrelor will prescribed in accordance with NICE guidance and licenced indications:

1. Group 5: Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)(in line with manufacturer's recommendations and licensing).

2. Group 6: Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)(in line with manufacturer's recommendations and licensing) The investigators will only begin recruitment to groups 5 and 6 once patient recruitment is completed in group 2

PROCEDURE LOG:

STEMI patients will be identified following admission for PPCI. Patient consent for this group shall be a 2 stage process. Initially, a shortened patient information sheet shall be read to the patient on admission prior to PPCI as to not delay treatment. Once verbal consent has been obtained a P2Y12 inhibitor ticagrelor will be administered to the patient as per current local and national guidance. The time of loading dose will be carefully recorded and the patient transferred to the cardiac catheterization suite for PPCI. After the insertion of the radial or femoral sheath, 15 ml (approx 3 teaspoonfuls in volume) of whole blood will be drawn from this sheath at 20 minutes post dosing (or as close to this time point as practicable) and also at the first balloon inflation time. A further 15 ml will be taken at 60 minutes post dosing (or as close as is practicable). The second stage of consent will occur after PPCI when the patient has been transferred to the ward and is pain free and has been able to rest. At this stage a full patient information sheet shall be given to the patient to read and written consent will be sought. A final 15ml blood sample will be taken after 4 hours post dosing, after which the patient's participation in this study will come to an end.

NSTEMI/UA (Unstable Angina) Potential patients will be approached by a member of the research team, who will offer the patient a full written patient information sheet and obtain written consent. Following consent the patient will have been administered a P2Y12 inhibitor (prasugrel or ticagrelor). The time of loading dose will be carefully recorded. 15 ml (approx 3 teaspoonfuls in volume ) of blood will be taken at 20 minutes, 60 minutes and then 4 hours post dosing, after which the patient's participation in this study will come to an end.

For both STEMI and NSTEMI/UA groups, aspirin will already have been given in the ambulance and will be assessed at 20 minutes after P2Y12 inhibitor loading and again at 60 minutes.

Each blood sample taken will undergo a series of tests which will encompass the presence and function of the antiplatelet medication after a patient has suffered either a major or minor heart attack.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics and Pharmacodynamics of Platelet P2Y12 Inhibitors in Patients Undergoing Percutaneous Coronary Intervention (PCI) for Acute Myocardial Infarction: A Pilot Study
• Actual Study Start Date: Mar 9, 2015
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: STEMI prasugrel Patients with diabetes mellitus admitted with STEMI who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel Loading (60mg) and maintenance (10mg per day).	Drug: Prasugrel
Other: STEMI clopidogrel Patients admitted with STEMI over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).	Drug: Clopidogrel
Other: NSTEMI clopidogrel Patients admitted with NSTEMI/UA over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).	Drug: Clopidogrel
Other: Patients with NSTEMI who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel loading (60mg) however: - i. After sample collection patients treated with intracoronary stent placement on the same day as loading will receive prasugrel maintenance dose (10mg per day) as per licensing agreement for prasugrel ii. After sample collection patients who are not stented after loading will receive clopidogrel maintenance dose (75mg per day).	Drug: Prasugrel; Drug: Clopidogrel
Other: Patients admitted with STEMI receiving ticagrelor loading Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)	Drug: ticagrelor
Other: Patients Admitted with NSTEMI receiving ticagrelor loading Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day).	Drug: ticagrelor

Outcome Measures

Primary Outcome Measures

1. Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by Verify Now Point of Care Assay and Expressed as P2Y12 Reaction Units (PRU) [Balloon Inflation as Baseline, 20, 60, 240 minutes]

2. Pharmacokinetic Quantification of Plasma Concentration of Clopidogrel and Prasugrel Active Metabolite and Ticagrelor Parent Compound and Active Metabolite Assessed Using Liquid Chromatography in Tandem With Mass Spectrometry (LC-MS/MS) Expressed as ng/ml [Balloon Inflation as Baseline, 20, 60, 240 minutes]

   The parent compound of Ticagrelor was also analysed within the same patient group of Ticagrelor as it is a directly acting agent that does not require metabolic conversion to its active form.

Secondary Outcome Measures

1. Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by VASP (Vasodilator Stimulated Phosphoprotein Phosphorylation) Flow Cytometry and Expressed as %PRI (Platelet Reactivity Index) [Balloon Inflation as Baseline, 20, 60, 240 minutes]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients presenting with STEMI for PCI (characterized by chest discomfort, and prominent STsegment elevation)

2. Patients presenting with NSTEMI (characterized by chest discomfort, raised levels of myocardial enzymes and/or STsegment depression or prominent T wave inversion)

3. Able to give verbal consent (STEMI patients pre procedure) and/or written consent (STEMI after procedure and NSTEMI patients prior to enrolment).

4. Age>18 years of age

5. Able to take Aspirin and either prasugrel or ticagrelor.

6. Have no concurrent septic or inflammatory illness

7. Thienopyridine naive

Exclusion Criteria:

1. Be unable to provide verbal and written consent

2. Allergic to aspirin or any of the P2Y12 antagonists in the trial

3. Have preexisting cardiogenic shock

4. Have a concurrent septic or inflammatory disease e.g. rheumatoid arthritis, lupus, pneumonia.

5. Already taking a P2Y12 inhibitor

6. Known bleeding diathesis

7. Patients under 75 years of age or under 60 kg or those who have had a previous stroke/transient ischaemic attack, will not be eligible for prasugrel but rather ticagrelor.

8. Patients with a history of intracranial haemorrhage will not receive prasugrel or ticagrelor but rather will receive treatment with clopidogrel.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Royal Wolverhampton NHS Trust	Wolverhampton	West Midlands	United Kingdom	WV10 0QP

Sponsors and Collaborators

• The Royal Wolverhampton Hospitals NHS Trust

Investigators

• Study Director: James Cotton, MD, FRCP, The Royal Wolverhampton NHS Trust

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 21, 2015

More Information

Publications

None provided.

• Responsible Party: The Royal Wolverhampton Hospitals NHS Trust
• ClinicalTrials.gov Identifier: NCT02376283
• Other Study ID Numbers: 2012-004-04-02-CARD
• First Posted: Mar 3, 2015
• Last Update Posted: Feb 10, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by The Royal Wolverhampton Hospitals NHS Trust: STEMI; NSTEMI; PPCI
• Additional relevant MeSH terms: Myocardial Infarction; Clopidogrel; Ticagrelor; Prasugrel Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Clopidogrel	Prasugrel	Ticagrelor
Arm/Group Description	STEMI (ST-segment elevation myocardial infarction) (n = 14) and NSTEMI (Non-ST segment elevation myocardial infarction) (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.
Period Title: Overall Study
STARTED	27	30	30
COMPLETED	27	30	30
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Clopidogrel	Prasugrel	Ticagrelor	Total
Arm/Group Description	STEMI (n = 14) and NSTEMI (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	Total of all reporting groups
Overall Participants	27	30	30	87
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 33.3%	19 63.3%	13 43.3%	41 47.1%
>=65 years	18 66.7%	11 36.7%	17 56.7%	46 52.9%
Sex: Female, Male (Count of Participants)
Female	8 29.6%	5 16.7%	6 20%	19 21.8%
Male	19 70.4%	25 83.3%	24 80%	68 78.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	27 100%	30 100%	30 100%	87 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by Verify Now Point of Care Assay and Expressed as P2Y12 Reaction Units (PRU)
Time Frame	Balloon Inflation as Baseline, 20, 60, 240 minutes

Outcome Measure Data

Analysis Population Description

The overall group consists of STEMI and NSTEMI participants -outcome measure is broken down into the time points for each specific sub-group reported separately by Row. These two categories represent a subpopulation within the Overall Number of Participants Analyzed, therefore it has been indicated how many participants were analyzed for each Row.

Arm/Group Title	Clopidogrel	Prasugrel	Ticagrelor
Arm/Group Description	STEMI (n = 14) and NSTEMI (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.
Measure Participants	27	30	30
STEMI at 20 mins	270.23 (38.56)	247.73 (48.78)	256.73 (50.81)
STEMI at balloon inflation	286.46 (33.12)	253.73 (57.17)	257.93 (61.12)
STEMI at 60 mins	293.46 (31.68)	262.87 (43.43)	225.20 (82.70)
STEMI at 240 mins	226.42 (69.44)	128.64 (89.16)	176.27 (84.92)
NSTEMI at 20 mins	213.21 (51.74)	125.80 (89.34)	172.80 (92.54)
NSTEMI at 60 mins	227.36 (61.19)	76.93 (99.24)	114.20 (122.22)
NSTEMI at 240 mins	214.00 (69.98)	31.87 (45.52)	23.00 (18.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor
	Comments	Continuous variables expressed as mean ± SD (standard deviation) and categorical variables as frequencies (%).Continuous variables analysed individually using student's independent sample t-tests. Categorical variables assessed using separate Fisher's exact (Chi-square) test.
	Type of Statistical Test	Other
	Comments	A p value < 0.05 was considered to be statistically significant.Comparison of means between groups assessed using ANOVA allowing comparison of more than 2 means and enabled assessment made of the relationship between different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Assessment made of relationship between groups-clop vs pras vs tic,rows of STEMI vs NSTEMI/UA and different time points.P-values reported are calculated values based on data collated during sample collection and review of clinical characteristics.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor
	Comments	STEMI- clop vs prasl vs tic
	Type of Statistical Test	Other
	Comments	Comparison of means between groups assessed using ANOVA allowing comparison of more than 2 means and enabled assessment made of the relationship between different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	ANOVA
	Comments	ANOVA F(3,36) = 12.282

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor
	Comments	NSTEMI- clopidogrel vs prasugrel vs ticagrelor
	Type of Statistical Test	Other
	Comments	Comparison of means between groups assessed using ANOVA allowing comparison of more than 2 means and enabled assessment made of the relationship between different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Assessment made of relationship between groups-clop vs pras vs tic,rows of STEMI vs NSTEMI/UA and different time points.P-values reported are calculated values based on data collated during sample collection and review of clinical characteristics.
	Method	ANOVA
	Comments	ANOVA F(2,40) = 29.097

2. Primary Outcome

Title	Pharmacokinetic Quantification of Plasma Concentration of Clopidogrel and Prasugrel Active Metabolite and Ticagrelor Parent Compound and Active Metabolite Assessed Using Liquid Chromatography in Tandem With Mass Spectrometry (LC-MS/MS) Expressed as ng/ml
Description	The parent compound of Ticagrelor was also analysed within the same patient group of Ticagrelor as it is a directly acting agent that does not require metabolic conversion to its active form.
Time Frame	Balloon Inflation as Baseline, 20, 60, 240 minutes

Outcome Measure Data

Analysis Population Description

The overall group consists of STEMI and NSTEMI participants -outcome measure is broken down into the time points for each specific sub-group reported separately by Row. These two categories represent a subpopulation within the Overall Number of Participants Analyzed, therefore it has been indicated how many participants were analyzed for each Row.

Arm/Group Title	Clopidogrel	Prasugrel	Ticagrelor	Ticagrelor Parent Compound
Arm/Group Description	STEMI (n = 14) and NSTEMI (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI/NSTEMI patients. (Ticagrelor was used in our centre only after the use of prasugrel was discontinued) The parent compound was also analysed as it is a directly acting agent that does not require metabolic conversion to its active form
Measure Participants	27	30	30	30
STEMI at 20 mins	39.12 (16.17)	14.27 (8.80)	0.16 (0.16)	9.04 (4.12)
STEMI at balloon inflation	107.83 (44.08)	24.20 (13.07)	1.64 (1.17)	28.56 (12.58)
STEMI at 60 mins	71.02 (27.21)	36.86 (13.27)	14.43 (7.28)	47.13 (24.09)
STEMI at 240 mins	32.41 (6.71)	38.44 (7.59)	53.38 (25.21)	84.92 (42.00)
NSTEMI at 20 mins	41.99 (25.27)	515.80 (126.84)	7.72 (5.10)	22.78 (10.27)
NSTEMI at 60 mins	93.35 (49.65)	194.59 (29.97)	58.40 (25.41)	84.13 (34.02)
NSTEMI at 240 mins	27.71 (6.90)	36.80 (4.59)	113.59 (19.20)	140.61 (36.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor, Ticagrelor Parent Compound
	Comments	Continuous variables were expressed as mean ± SEM (Standard Error of Measurement) and categorical variables as frequencies (%). Continuous variables were analysed individually using student's independent sample t-tests. Categorical variables were assessed using separate Fisher's exact (Chi-square) test.
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel active metabolite vs prasugrel active metabolite vs ticagrelor parent compound and active metabolite), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Assessment made of relationship between groups-clop vs pras vs tic, rows of STEMI vs NSTEMI/UA and different time points. P-values reported are calculated values based on data collated during sample collection and review of clinical characteristics.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor, Ticagrelor Parent Compound
	Comments	STEMI- different drugs (as stated above)
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel active metabolite vs prasugrel active metabolite vs ticagrelor parent compound and active metabolite), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	=0.123
	Comments
	Method	ANOVA
	Comments	ANOVA F(6,56)=1.707

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor, Ticagrelor Parent Compound
	Comments	NSTEMI- different drugs (as stated above)
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel active metabolite vs prasugrel active metabolite vs ticagrelor parent compound and active metabolite), different clinical states (STEMI vs NSTEMI/UA (Unstable angina)) and different time points.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Assessment made of relationship between groups-clop vs pras vs tic, rows of STEMI vs NSTEMI/UA and different time points. P-values reported are calculated values based on data collated during sample collection and review of clinical characteristics.
	Method	ANOVA
	Comments	ANOVA F(4,62)=18.932

3. Secondary Outcome

Title	Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by VASP (Vasodilator Stimulated Phosphoprotein Phosphorylation) Flow Cytometry and Expressed as %PRI (Platelet Reactivity Index)
Time Frame	Balloon Inflation as Baseline, 20, 60, 240 minutes

Outcome Measure Data

Analysis Population Description

The overall group consists of STEMI and NSTEMI participants -outcome measure is broken down into the time points for each specific sub-group reported separately by Row. These two categories represent a subpopulation within the Overall Number of Participants Analyzed, therefore it has been indicated how many participants were analyzed for each Row.

Arm/Group Title	Clopidogrel	Prasugrel	Ticagrelor
Arm/Group Description	STEMI (n = 14) and NSTEMI (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.	STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.
Measure Participants	27	30	30
STEMI at 20 mins	76.29 (8.77)	46.25 (13.91)	79.75 (9.20)
STEMI at balloon inflation	74.86 (9.00)	41.13 (12.71)	74.63 (11.42)
STEMI at 60 mins	71.57 (11.68)	50.50 (11.88)	76.25 (11.12)
STEMI at 240 mins	63.14 (13.26)	57.00 (10.39)	51.38 (14.06)
NSTEMI at 20 mins	75.17 (2.74)	33.27 (10.66)	62.00 (8.79)
NSTEMI at 60 mins	76.75 (4.35)	21.91 (9.72)	33.17 (17.73)
NSTEMI at 240 mins	61.83 (5.82)	15.18 (5.85)	20.17 (10.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor
	Comments	Continuous variables were expressed as mean ± SD and categorical variables as frequencies (%). Continuous variables were analysed individually using student's independent sample t-tests. Categorical variables were assessed using separate Fisher's exact (Chi-square) test.
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA) and different time points.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Assessment made of relationship between groups-clop vs pras vs tic, rows of STEMI vs NSTEMI/UA and different time points. P-values reported are calculated values based on data collated during sample collection and review of clinical characteristics.
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Prasugrel, Ticagrelor
	Comments	Continuous variables were expressed as mean ± SD and categorical variables as frequencies (%). Continuous variables were analysed individually using student's independent sample t-tests. Categorical variables were assessed using separate Fisher's exact (Chi-square) test.
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA) and different time points.
Statistical Test of Hypothesis	p-Value	=0.810
	Comments	STEMI- clopidogrel vs prasugrel vs ticagrelor
	Method	ANOVA
	Comments	ANOVA F(3,17) = 0.321

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel, Ticagrelor
	Comments	Continuous variables were expressed as mean ± SD and categorical variables as frequencies (%). Continuous variables were analysed individually using student's independent sample t-tests. Categorical variables were assessed using separate Fisher's exact (Chi-square) test.
	Type of Statistical Test	Other
	Comments	Comparison of means between groups was assessed using analysis of variance (ANOVA) technique. ANOVA allowed for a comparison of more than two means and enabled an assessment to be made of the relationship between, different drugs (clopidogrel vs prasugrel vs ticagrelor), different clinical states (STEMI vs NSTEMI/UA) and different time points.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	NSTEMI- clopi vs pras vs tic
	Method	ANOVA
	Comments	ANOVA F(2,25) = 14.103

Adverse Events

Time Frame	4 hours
Arm/Group Title	Clopidogrel		Prasugrel		Ticagrelor
Arm/Group Description	STEMI (n = 14) and NSTEMI (n = 13) patients were administered a clopidogrel 600mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.		STEMI (n = 15) and NSTEMI (n = 15) patients were administered a prasugrel 90mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition were obtained. Plasma samples to allow for pharmacokinetic quantification of active metabolites were extracted from whole blood samples collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.		STEMI (n = 15) and NSTEMI (n = 15) patients were administered a ticagrelor 180mg loading dose and whole blood samples (15ml) for pharmacodynamic assessment of the degree of platelet inhibition and pharmacokinetic quantification of parent compound and active metabolites were collected. Samples were collected at 20 minutes, 60 minutes and 240 minutes post loading. In the STEMI group an additional sample was collected at the time of angioplasty. The participants involvement in the study ceased following the collection of the 240-minute blood sample.
All Cause Mortality
	Clopidogrel		Prasugrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Clopidogrel		Prasugrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Clopidogrel		Prasugrel		Ticagrelor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/30 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.