Influence of Morphine on Pharmacokinetics and Pharmacodyn... | NCT02217878

Label	Type	Description	Intervention Names
Morphine	Active Comparator	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor	Drug: Morphine Drug: Ticagrelor
Placebo	Placebo Comparator	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor	Drug: Placebo Drug: Ticagrelor

Name	Type	Description	Arm Group Labels	Other Names
Morphine	Drug	IV bolus injection	Morphine	Morphine sulfate

Measure	Description	Time Frame
Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)	Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose	prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose

Measure	Description	Time Frame
Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)	Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose	prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Maximum Concentration of Ticagrelor

Name	Affiliation	Role
Prof. Jacek Kubica, MD, PhD	Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Cardiology Department, Dr. A. Jurasz University Hospital		Bydgoszcz	Kuyavian-Pomeranian Voivodeship	85-094	Poland

PubMed Identifier	Type	Citation	Retractions
26491112	Derived	Kubica J, Adamski P, Ostrowska M, Sikora J, Kubica JM, Sroka WD, Stankowska K, Buszko K, Navarese EP, Jilma B, Siller-Matula JM, Marszall MP, Rosc D, Kozinski M. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016 Jan 14;37(3):245-52. doi: 10.1093/eurheartj/ehv547. Epub 2015 Oct 21.
25925591

ID	Title	Description
FG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
FG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)

Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose

Posted

Mean

Standard Deviation

ng*h/mL

prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG00035 OG00135

Title

Denominators

Categories

Title	Measurements
	OG0006307± 4359 OG0019791± 5136

Secondary

Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)

Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose

Posted

Mean

Standard Deviation

ng*h/mL

prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Maximum Concentration of Ticagrelor

Maximum concentration (Cmax) of ticagrelor

Posted

Mean

Standard Deviation

ng/mL

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Maximum Concentration of AR-C124910XX

Maximum concentration (Cmax) of AR-C124910XX

Posted

Median

Inter-Quartile Range

ng/mL

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Time to Maximum Concentration for Ticagrelor

Time to maximum concentration (Tmax) for ticagrelor

Posted

Median

Inter-Quartile Range

hours

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Time to Maximum Concentration for AR-C124910XX

Time to maximum concentration (Tmax) for AR-C124910XX

Posted

Median

Inter-Quartile Range

hours

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)

Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose

Posted

Median

Inter-Quartile Range

ng*h/mL

prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)

Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose

Posted

Median

Inter-Quartile Range

ng*h/mL

prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

prior to the initial ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

30 minutes post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

1 hour post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

2 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

3 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

4 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

6 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Reactivity Index Assessed by VASP Assay

Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)

Posted

Median

Inter-Quartile Range

Platelet Reactivity Index (%)

12 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

prior to the initial ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

30 minutes post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

1 hour post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

2 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

3 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

4 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

6 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry

Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

Platelet Arbitrary Aggregation Units

12 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

prior to the initial ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

30 minutes post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

1 hour post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

2 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

3 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

4 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

6 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

P2Y12 Reaction Units Assessed by VerifyNow

P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

P2Y12 Reaction Units

12 hours post ticagrelor dose

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP

Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP

Posted

Number

Percentage of Patients With HPR

2 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA

Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Number

Percentage of Patients With HPR

2 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow

Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Number

Percentage of Patients With HPR

2 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP

Posted

Median

Inter-Quartile Range

hours

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA

According to the study protocol multiple electrode aggregometry pharmacodynamic evaluation was performed in all patients except for those treated with glycoprotein (GP) IIb/IIIa receptor inhibitors.

Posted

Median

Inter-Quartile Range

hours

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Secondary

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow

Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow

In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.

Posted

Median

Inter-Quartile Range

hours

12 hours

ID	Title	Description
OG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
OG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose

Units	Counts
Participants	OG000

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Stent thrombosis	Vascular disorders		Systematic Assessment		EG0001 affected35 at risk EG0010 affected35 at risk
Pulmonary oedema	Cardiac disorders		Systematic Assessment		EG0000 affected35 at risk EG0012 affected35 at risk

Term	Organ System	Assessment Type	Statistical Information
TIMI minor bleeding	Vascular disorders	Systematic Assessment	EG0000 affected35 at risk EG0014 affected35 at risk
TIMI minimal bleeding	Vascular disorders	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk
Bradyarrhythmic event	Cardiac disorders	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk

ID	Term
D009203	Myocardial Infarction
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases
D007238	Infarction
D007511	Ischemia
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009336	Necrosis

ID	Term
D009022	Morphine Derivatives
D009019	Morphinans
D053610	Opiate Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D006572	Heterocyclic Compounds, Bridged-Ring
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D010616	Phenanthrenes
D011084	Polycyclic Aromatic Hydrocarbons
D011083	Polycyclic Compounds
D000241	Adenosine
D011684	Purine Nucleosides
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides

ID	Title	Description
BG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose
BG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Morphine	morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor Morphine: IV bolus injection Ticagrelor: 180 mg loading dose			1	35	5	35
EG001	Placebo	sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor Placebo: IV bolus injection Ticagrelor: 180 mg loading dose			2	35	7	35