A 30 day study to evaluate efficacy and safety of pre-hospital vs. in-hospital initiation of ticagrelor therapy in STEMI patients planned for Percutaneous Coronary Intervention (PCI) - ATLANTIC

Study identifier:D5130L00006

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 30 day international, randomized, parallel-group, double-blind, placebo-controlled phase IV study to evaluate efficacy and safety of pre-hospital vs. in-hospital initiation of ticagrelor therapy in STEMI patients planned for PCI.

Medical condition

myocardial infarction

Phase

Phase 4

Healthy volunteers

Study drug

Ticagrelor, Placebo

Sex

All

Actual Enrollment

1875

Study type

Interventional

Age

18 Years - 150 Years

Date

Study Start Date: 01 Sept 2011

Primary Completion Date: 01 Nov 2013

Study Completion Date: 01 Nov 2013

Study design

Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2015 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

ALGIERS, Algeria

Location

Research Site

BLIDA, Algeria

Location

Research Site

Herston, Australia

Location

Research Site

Southport, Australia

Location

Research Site

Woolloongabba, Australia

Location

Research Site

Graz, Austria

Location

Research Site

Innsbruck, Austria

Location

Research Site

Wien, Austria

Arms	Assigned Interventions
Experimental: Ticagrelor Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.	Drug: Ticagrelor Oral Ticagrelor loading dose (180 mg) followed by matching placebo
Experimental: Placebo Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.	Drug: Placebo Placebo followed by oral Ticagrelor loading dose (180 mg)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were randomized in pre-hospital settings at 102 Emergency Medical Services between September 2011 and October 2013. 1875 patients were recruited in the study, 1862 consented patients were randomized.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Participant Flow: Overall Study

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
STARTED	909^[1]	953^[2]
Modified Intent to Treat population	906^[3]	952^[4]
Safety population	908^[5]	950^[6]
COMPLETED	844^[7]	897^[8]
NOT COMPLETED	65	56
Withdrawal by Subject	13	23
Death	30	19
Protocol Violation	10	7
Lost to Follow-up	3	1
Had other reason	9	6

[1]	based on randomized treatment
[2]	based on randomized treatment
[3]	based on randomized treatment
[4]	based on randomized treatment
[5]	based on actual treatment
[6]	based on actual treatment
[7]	based on randomized treatment
[8]	based on randomized treatment

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Baseline Measures

	Pre-hospital Ticagrelor	In-hospital Ticagrelor	Total
Number of Participants [units: Participants]	909	953	1862
Age Continuous [units: Years] Mean ± Standard Deviation Years	60.6 ± 12.38	61.0 ± 12.49	60.8 ± 12.43
Gender, Male/Female [units: participants]
Female	173	196	369
Male	736	757	1493
Diabetes mellitus [units: patients]
yes	115	138	253
no/unknown	794	815	1609
TIMI risk score ^[1] [units: patients]
0-2	552	573	1125
3-6	337	365	702
>6	20	15	35
Killip class ^[2] [units: patients]
I	819	862	1681
II, III, IV	51	43	94
unknown	39	48	87
First medical contact [units: patients]
in ambulance	689	723	1412
in emergency department	220	230	450
PCI ^[3] [units: Patients]
yes	800	830	1630
no	109	123	232
type of PCI ^[4] [units: patients]
with stent	760	776	1536
without stent	40	54	94
Time between the 2 loading doses [units: minutes] Median ( Inter-Quartile Range )	32 (22 to 45)	30 (22 to 43)	31 (22 to 44)

Outcome Measures

1. Primary Outcome Measure: Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 of MI culprit vessel at initial angiography (co-primary endpoint) [ Time Frame: At initial angiography, pre PCI ]

Measure Type	Primary
Measure Name	Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 of MI culprit vessel at initial angiography (co-primary endpoint)
Measure Description	(TIMI) flow grade classification is used to assess coronary blood flow in acute coronary syndromes. grade 0:no reperfusion, grade 1: penetration without perfusion, grade 2: Partial reperfusion, grade 3: complete perfusion.
Time Frame	At initial angiography, pre PCI
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT, on patients with non missing values

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	824	856
Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 of MI culprit vessel at initial angiography (co-primary endpoint) [units: patients]	143	145

Statistical Analysis 1 for Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 of MI culprit vessel at initial angiography (co-primary endpoint)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.8214
Odds Ratio (OR)^[5]	1.030
95% Confidence Interval	( 0.799 to 1.327 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	pvalue at 0.025 , adjusted for multiple comparisons
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: ST-segment elevation resolution pre PCI ≥70% (co-primary endpoint) [ Time Frame: Between baseline and PCI ]

Measure Type	Primary
Measure Name	ST-segment elevation resolution pre PCI ≥70% (co-primary endpoint)
Measure Description	ST segment elevation resolution is the mean ST elevation pre-hospital minus the mean STelevation pre-PCI divided by the mean ST elevation pre-hospital. It is expressed as a percentage and split in 2 categories , complete (≥70%) versus incomplete (<70%) resolution.
Time Frame	Between baseline and PCI
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT, on patients with non missing values

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	774	824
ST-segment elevation resolution pre PCI ≥70% (co-primary endpoint) [units: patients]	102	102

Statistical Analysis 1 for ST-segment elevation resolution pre PCI ≥70% (co-primary endpoint)

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.6322
Odds Ratio (OR)^[5]	1.074
95% Confidence Interval	( 0.801 to 1.441 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P value at 0.025 adjusted for multiple comparisons
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: 1st Composite clinical endpoint [ Time Frame: during the 30 days of treatment ]

Measure Type	Secondary
Measure Name	1st Composite clinical endpoint
Measure Description	death/MI/stroke/urgent revascularization/stent thrombosis. Adjudicated events except death
Time Frame	during the 30 days of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	906	952
1st Composite clinical endpoint [units: patients]	41	42

Statistical Analysis 1 for 1st Composite clinical endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.9056
Odds Ratio (OR)^[5]	1.027
95% Confidence Interval	( 0.661 to 1.595 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: 2nd composite clinical endpoint [ Time Frame: within 30 days of study ]

Measure Type	Secondary
Measure Name	2nd composite clinical endpoint
Measure Description	Death/MI/urgent revascularization. Adjudicated events except death
Time Frame	within 30 days of study
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	906	952
2nd composite clinical endpoint [units: patients]	39	34

Statistical Analysis 1 for 2nd composite clinical endpoint

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.4168
Odds Ratio (OR)^[5]	1.215
95% Confidence Interval	( 0.760 to 1.942 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Definite stent thrombosis [ Time Frame: during 30 days of treatment ]

Measure Type	Secondary
Measure Name	Definite stent thrombosis
Measure Description	Definite stent thrombosis is considered to have occurred by either angiographic or pathologic confirmation. It is an adjudicated endpoint
Time Frame	during 30 days of treatment
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	906	952
Definite stent thrombosis [units: patients]	2	11

Statistical Analysis 1 for Definite stent thrombosis

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.0307
Odds Ratio (OR)^[5]	0.189
95% Confidence Interval	( 0.042 to 0.856 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: TIMI flow grade 3 post -PCI [ Time Frame: at coroangiography post-PCI ]

Measure Type	Secondary
Measure Name	TIMI flow grade 3 post -PCI
Measure Description	TIMI) flow grade 3 is complete perfusion post-PCI.
Time Frame	at coroangiography post-PCI
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT, on patients with non missing TIMI flow grade values

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	760	784
TIMI flow grade 3 post -PCI [units: patients]	625	630

Statistical Analysis 1 for TIMI flow grade 3 post -PCI

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.344
Odds Ratio (OR)^[5]	1.132
95% Confidence Interval	( 0.876 to 1.462 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: ST segment elevation resolution post-PCI >= 70% [ Time Frame: Between baseline and ECG 60 mn post-PCI ]

Measure Type	Secondary
Measure Name	ST segment elevation resolution post-PCI >= 70%
Measure Description	ST segment elevation resolution post PCI >=70% is defined as complete resolution
Time Frame	Between baseline and ECG 60 mn post-PCI
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT on patients with non missing ECG values

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	713	743
ST segment elevation resolution post-PCI >= 70% [units: patients]	410	390

Statistical Analysis 1 for ST segment elevation resolution post-PCI >= 70%

Groups^[1]	Pre-hospital Ticagrelor
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.0547
Odds Ratio (OR)^[5]	1.225
95% Confidence Interval	( 0.996 to 1.506 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI [ Time Frame: during PCI ]

Measure Type	Secondary
Measure Name	Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI
Measure Description	Glycoprotein (GP) IIb/IIIa inhibitors are often used as a rescue or bailout therapy to manage complications arising during percutaneous coronary intervention.
Time Frame	during PCI
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mITT

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	906	952
Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI [units: patients]	78	100

Statistical Analysis 1 for Thrombotic bail-out with GPIIb/IIIa inhibitors at initial PCI

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Regression, Logistic
P-Value^[4]	0.1660
Odds Ratio (OR)^[5]	0.803
95% Confidence Interval	( 0.588 to 1.096 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Major Bleeds within 48 hours [ Time Frame: within 48 hours of first dose ]

Measure Type	Secondary
Measure Name	Major Bleeds within 48 hours
Measure Description	non CABG related bleeds, (PLATO definition) include Life threatening and other major bleeds
Time Frame	within 48 hours of first dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	908	950
Major Bleeds within 48 hours [units: patients]	16	15

No statistical analysis provided for Major Bleeds within 48 hours

10. Secondary Outcome Measure: Minor and Major bleedings within 48 hours [ Time Frame: within 48 hours of first dose ]

Measure Type	Secondary
Measure Name	Minor and Major bleedings within 48 hours
Measure Description	non CABG related bleeds (PLATO definition)
Time Frame	within 48 hours of first dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	908	950
Minor and Major bleedings within 48 hours [units: patients]	24	24

No statistical analysis provided for Minor and Major bleedings within 48 hours

11. Secondary Outcome Measure: Major Bleeds after 48 hours [ Time Frame: after 48hours post-first dose ]

Measure Type	Secondary
Measure Name	Major Bleeds after 48 hours
Measure Description	non CABG related bleeds (PLATO definition) include life threatening and other major bleedings
Time Frame	after 48hours post-first dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
safety

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	908	950
Major Bleeds after 48 hours [units: patients]	11	11

No statistical analysis provided for Major Bleeds after 48 hours

12. Secondary Outcome Measure: Minor and Major bleeds after 48 hours [ Time Frame: after 48 hours post first dose ]

Measure Type	Secondary
Measure Name	Minor and Major bleeds after 48 hours
Measure Description	non CABG related bleeds (PLATO definition)
Time Frame	after 48 hours post first dose
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
safety

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Measured Values

	Pre-hospital Ticagrelor	In-hospital Ticagrelor
Number of Participants Analyzed [units:participants]	908	950
Minor and Major bleeds after 48 hours [units: patients]	18	16

No statistical analysis provided for Minor and Major bleeds after 48 hours

Serious Adverse Events

Time Frame	within 30 days of study
Additional Description	Actual Treatment Safety analysis set concerns 1858 patients- Ticagrelor pre-hosp:908 and Ticagrelor in-hosp: 950. 4 patients receiveived study medication not according to randomization assignment

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Serious Adverse Events

Pre-hospital Ticagrelor

In-hospital Ticagrelor

Total, serious adverse events

# participants affected / at risk

140/908 (15.42%)

143/950 (15.05%)

General disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

13/908 (1.43%)

13/950 (1.37%)

Respiratory, thoracic and mediastinal disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

13/908 (1.43%)

13/950 (1.37%)

Gastrointestinal disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

11/908 (1.21%)

8/950 (0.84%)

Infections and infestations

On treatment SAE (incl. bleeding)

# participants affected / at risk

10/908 (1.10%)

4/950 (0.42%)

Injury, poisoning and procedural complications

On treatment SAE (incl. bleeding)

# participants affected / at risk

9/908 (0.99%)

4/950 (0.42%)

Cardiac disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

91/908 (10.02%)

101/950 (10.63%)

Nervous system disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

7/908 (0.77%)

7/950 (0.74%)

Vascular disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

7/908 (0.77%)

5/950 (0.53%)

Renal and urinary disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

5/908 (0.55%)

3/950 (0.32%)

Investigations

On treatment SAE (incl. bleeding)

# participants affected / at risk

5/908 (0.55%)

1/950 (0.11%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

On treatment SAE (incl. bleeding)

# participants affected / at risk

3/908 (0.33%)

3/950 (0.32%)

Hepatobiliary disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

2/908 (0.22%)

3/950 (0.32%)

Musculoskeletal and connective tissue disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

2/908 (0.22%)

2/950 (0.21%)

Blood and lymphatic system disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

2/908 (0.22%)

2/950 (0.21%)

Psychiatric disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

1/908 (0.11%)

2/950 (0.21%)

Metabolism and nutrition disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

2/908 (0.22%)

0/950 (0.00%)

Congenital, familial and genetic disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

0/908 (0.00%)

1/950 (0.11%)

Ear and labyrinth disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

1/908 (0.11%)

0/950 (0.00%)

Skin and subcutaneous tissue disorders

On treatment SAE (incl. bleeding)

# participants affected / at risk

0/908 (0.00%)

1/950 (0.11%)

†	Events were collected by systematic assessment
1	Term from vocabulary,

Other Adverse Events

Time Frame	within 30 days of study
Additional Description	Actual Treatment Safety analysis set concerns 1858 patients- Ticagrelor pre-hosp:908 and Ticagrelor in-hosp: 950. 4 patients receiveived study medication not according to randomization assignment

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Pre-hospital Ticagrelor	Loading dose of Ticagrelor (180 mg) followed by matching placebo. After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.
In-hospital Ticagrelor	Placebo followed by a loading dose of Ticagrelor (180 mg). After the loading dose the patient will receive Ticagrelor (90 mg bid) for 30 days.

Other Adverse Events

Pre-hospital Ticagrelor

In-hospital Ticagrelor

Total, other (not including serious) adverse events

# participants affected / at risk

553/908 (60.90%)

563/950 (59.26%)

Cardiac disorders

On treatment AE (Incl. Bleeding)

# participants affected / at risk

355/908 (39.10%)

373/950 (39.26%)

Gastrointestinal disorders

On-treatment AE (Incl. Bleeding)

# participants affected / at risk

165/908 (18.17%)

190/950 (20.00%)

Respiratory, thoracic and mediastinal disorders

On-treatment AE (Incl. Bleeding)

# participants affected / at risk

161/908 (17.73%)

174/950 (18.32%)

General disorders

On-treatment AE (Incl. Bleeding)

# participants affected / at risk

130/908 (14.32%)

137/950 (14.42%)

Vascular disorders

On-treatment (Inc. Bleeding)

# participants affected / at risk

84/908 (9.25%)

70/950 (7.37%)

Nervous system disorders

On-treatment (Inc. Bleeding)

# participants affected / at risk

60/908 (6.61%)

72/950 (7.58%)

Infections and infestations

On-treatment (Inc. Bleeding)

# participants affected / at risk

54/908 (5.95%)

56/950 (5.89%)

Injury, poisoning and procedural complications

On-treatment (Inc. Bleeding)

# participants affected / at risk

54/908 (5.95%)

32/950 (3.37%)

Psychiatric disorders

On-treatment (Inc. Bleeding)

# participants affected / at risk

52/908 (5.73%)

46/950 (4.84%)

Metabolism and nutrition disorders

On-treatment (inc. Bleeding)

# participants affected / at risk

75/908 (8.26%)

66/950 (6.95%)

†	Events were collected by systematic assessment
1	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This urgent setting study included 8.6% of patients with symptoms of MI in ambulance but having finally not a STEMI diagnosis in cathlab. No prespecified hypothesis and procedure for adjustment was made on secondary endpoints.

Results Point of Contact

Name/Title:	Dr Tomas Andersson MD
Organization:	AstraZeneca
Phone	00 46 31 77 61966
E-mail:	[email protected]

Documents available

D5130L00006_Protocol
Download
D5130L00006_CSR_Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dr Judith Hsia

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

D5130L00006_Protocol

D5130L00006_CSR_Synopsis

Trial Results Summaries