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Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Acute Myocardial Infarction (IMPRESSION)

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ClinicalTrials.gov Identifier: NCT02217878
Recruitment Status : Completed
First Posted : August 15, 2014
Results First Posted : March 3, 2016
Last Update Posted : September 12, 2017
Sponsor:
Information provided by (Responsible Party):
Jacek Kubica, Collegium Medicum w Bydgoszczy

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions ST-segment Elevation Myocardial Infarction
Non-ST-segment Elevation Myocardial Infarction
VA Drug Interactions
Interventions Drug: Morphine
Drug: Placebo
Drug: Ticagrelor
Enrollment 74
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Morphine Placebo
Hide Arm/Group Description

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Period Title: Overall Study
Started 37 37
Completed 35 35
Not Completed 2 2
Reason Not Completed
required morphine due to chest pain             1             2
initial diagnosis of STEMI not confirmed             1             0
Arm/Group Title Morphine Placebo Total
Hide Arm/Group Description

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Total of all reporting groups
Overall Number of Baseline Participants 35 35 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 35 participants 70 participants
60.7  (10.5) 62.5  (10.5) 61.5  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
Female
12
  34.3%
7
  20.0%
19
  27.1%
Male
23
  65.7%
28
  80.0%
51
  72.9%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 35 participants 35 participants 70 participants
27.6  (4.3) 27.4  (4.0) 27.5  (4.2)
STEMI  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
24 21 45
GP IIb/IIIa administration  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
10 6 16
Hypertension  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
15 21 36
Diabetes mellitus  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
8 5 13
Dyslipidaemia  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
30 31 61
Current smoker  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
17 14 31
Prior AMI  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
5 8 13
Prior PCI  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
4 9 13
Prior CABG  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
0 0 0
Prior non-severe heart failure  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
0 3 3
Prior non-haemorrhagic stroke  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
1 0 1
Peripheral arterial disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
3 1 4
Chronic renal disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
1 2 3
Chronic obstructive pulmonary disease  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
2 0 2
Gout  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants 35 participants 70 participants
1 2 3
1.Primary Outcome
Title Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h)
Hide Description Exposure to ticagrelor during the first 12 hours after ticagrelor loading dose
Time Frame prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
6307  (4359) 9791  (5136)
2.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h)
Hide Description Exposure to ticagrelor metabolite during the first 12 hours after ticagrelor loading dose
Time Frame prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
1503  (1138) 2388  (1555)
3.Secondary Outcome
Title Maximum Concentration of Ticagrelor
Hide Description Maximum concentration (Cmax) of ticagrelor
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Mean (Standard Deviation)
Unit of Measure: ng/mL
1156  (771) 1683  (847)
4.Secondary Outcome
Title Maximum Concentration of AR-C124910XX
Hide Description Maximum concentration (Cmax) of AR-C124910XX
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
1085
(508 to 1709)
1043
(792 to 1572)
5.Secondary Outcome
Title Time to Maximum Concentration for Ticagrelor
Hide Description Time to maximum concentration (Tmax) for ticagrelor
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: hours
4
(3 to 12)
2
(2 to 4)
6.Secondary Outcome
Title Time to Maximum Concentration for AR-C124910XX
Hide Description Time to maximum concentration (Tmax) for AR-C124910XX
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: hours
4
(3 to 12)
4
(3 to 6)
7.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h)
Hide Description Exposure to ticagrelor during the first 6 hours after ticagrelor loading dose
Time Frame prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: ng*h/mL
2491
(189 to 5764)
5587
(2810 to 8546)
8.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6)
Hide Description Exposure to ticagrelor metabolite during the first 6 hours after ticagrelor loading dose
Time Frame prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: ng*h/mL
472
(0 to 1036)
1001
(643 to 1666)
9.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame prior to the initial ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
88.5
(82.9 to 93.5)
88.3
(81.5 to 94.0)
10.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 30 minutes post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
83.2
(74.5 to 89.7)
73.9
(42.6 to 87.7)
11.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 1 hour post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
70.2
(34.1 to 87.2)
42.0
(25.6 to 81.2)
12.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 2 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
52.1
(21.7 to 80.5)
26.2
(18.7 to 52.1)
13.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 3 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
37.8
(24.7 to 75.1)
26.0
(13.1 to 52.4)
14.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 4 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
36.9
(19.1 to 64.1)
23.2
(14.3 to 43.4)
15.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 6 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
27.9
(18.2 to 44.1)
19.7
(12.7 to 33.0)
16.Secondary Outcome
Title Platelet Reactivity Index Assessed by VASP Assay
Hide Description Platelet Reactivity Index (PRI) evaluated by VASP assay (cut-off value for high platelet reactivity: PRI >50%)
Time Frame 12 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Reactivity Index (%)
27.5
(17.0 to 42.3)
15.6
(12.3 to 33.1)
17.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame prior to the initial ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
85
(70 to 102)
77
(54 to 95)
18.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 30 minutes post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
86
(53 to 99)
48
(22 to 89)
19.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 1 hour post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
59
(31 to 86)
23
(17 to 60)
20.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 2 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
31
(20 to 71)
23
(10 to 36)
21.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 3 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 35
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
27
(18 to 55)
17
(10 to 23)
22.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 4 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
29
(10 to 44)
13
(9 to 22)
23.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 6 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
19
(9 to 34)
11
(5 to 15)
24.Secondary Outcome
Title Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
Hide Description Platelet reactivity assessed by Multiple Electrode Aggregometry (cut-off value for high platelet reactivity: AUC >46 Platelet Arbitrary Aggregation Units)
Time Frame 12 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: Platelet Arbitrary Aggregation Units
19
(10 to 27)
11
(7 to 16)
25.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame prior to the initial ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
232.5
(197.0 to 270.0)
238.5
(194.0 to 267.0)
26.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 30 minutes post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
268.5
(202.0 to 299.0)
210.5
(118.0 to 266.0)
27.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 1 hour post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
206.5
(88.0 to 266.0)
117.0
(10.0 to 233.0)
28.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 2 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
137.0
(27.0 to 251.0)
44.0
(7.0 to 119.0)
29.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 3 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
113.0
(31.0 to 221.0)
15.0
(4.0 to 52.0)
30.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 4 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
50.5
(8.0 to 165.0)
9.0
(4.0 to 72.0)
31.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 6 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
44.5
(6.0 to 171.0)
8.0
(3.0 to 21.0)
32.Secondary Outcome
Title P2Y12 Reaction Units Assessed by VerifyNow
Hide Description P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame 12 hours post ticagrelor dose
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: P2Y12 Reaction Units
9.0
(4.0 to 116.0)
7.5
(3.0 to 48.0)
33.Secondary Outcome
Title Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
Hide Description Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Measure Type: Number
Unit of Measure: Percentage of Patients With HPR
57 29
34.Secondary Outcome
Title Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA
Hide Description Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Measure Type: Number
Unit of Measure: Percentage of Patients With HPR
40 14
35.Secondary Outcome
Title Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow
Hide Description Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Measure Type: Number
Unit of Measure: Percentage of Patients With HPR
36 19
36.Secondary Outcome
Title Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP
Hide Description Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: hours
2.0
(1.0 to 6.0)
1
(0.5 to 3)
37.Secondary Outcome
Title Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Hide Description Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 25 29
Median (Inter-Quartile Range)
Unit of Measure: hours
2.0
(1.0 to 4.0)
1.0
(0.5 to 2.0)
38.Secondary Outcome
Title Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Hide Description Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
Time Frame 12 hours
Hide Outcome Measure Data
Hide Analysis Population Description
In line with the study protocol, VerifyNow pharmacodynamic evaluation involved >30% of the overall study population.
Arm/Group Title Morphine Placebo
Hide Arm/Group Description:

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

Overall Number of Participants Analyzed 26 35
Median (Inter-Quartile Range)
Unit of Measure: hours
1.0
(0 to 3.0)
0.5
(0 to 1.0)
Time Frame 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Morphine Placebo
Hide Arm/Group Description

morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor

Morphine: IV bolus injection

Ticagrelor: 180 mg loading dose

sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor

Placebo: IV bolus injection

Ticagrelor: 180 mg loading dose

All-Cause Mortality
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/35 (2.86%)   2/35 (5.71%) 
Cardiac disorders     
Pulmonary oedema   0/35 (0.00%)  2/35 (5.71%) 
Vascular disorders     
Stent thrombosis   1/35 (2.86%)  0/35 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Morphine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   5/35 (14.29%)   7/35 (20.00%) 
Cardiac disorders     
Bradyarrhythmic event   1/35 (2.86%)  2/35 (5.71%) 
Gastrointestinal disorders     
Nausea   2/35 (5.71%)  0/35 (0.00%) 
Vomiting   2/35 (5.71%)  0/35 (0.00%) 
Vascular disorders     
TIMI minor bleeding   0/35 (0.00%)  4/35 (11.43%) 
TIMI minimal bleeding   0/35 (0.00%)  1/35 (2.86%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Jacek Kubica
Organization: Collegium Medicum, Nicolaus Copernicus University
Phone: +485854023
EMail: jkubica@cm.umk.pl
Layout table for additonal information
Responsible Party: Jacek Kubica, Collegium Medicum w Bydgoszczy
ClinicalTrials.gov Identifier: NCT02217878    
Other Study ID Numbers: CMUMK202
First Submitted: August 14, 2014
First Posted: August 15, 2014
Results First Submitted: February 4, 2016
Results First Posted: March 3, 2016
Last Update Posted: September 12, 2017