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

• Sponsor: Collegium Medicum w Bydgoszczy (Other)
• Overall Status: Completed
• CT.gov ID: NCT02217878
• Collaborator: (none)
• Enrollment: 74
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 7.4

Study Details

Study Description

Brief Summary

The purpose of the IMPRESSION study is to determine whether intravenous administration of morphine prior to ticagrelor administration in ST-segment elevation myocardial infarction (STEMI) patients and in non-ST-segment elevation myocardial infarction (NSTEMI) patients alters the plasma concentrations of ticagrelor and its active metabolite and whether it is associated with any negative impact on the antiplatelet effect of ticagrelor.

Condition or Disease	Intervention/Treatment	Phase
ST-segment Elevation Myocardial Infarction; Non-ST-segment Elevation Myocardial Infarction; VA Drug Interactions	Drug: Morphine; Drug: Placebo; Drug: Ticagrelor	Phase 4

Detailed Description

The European Society of Cardiology and American Heart Association guidelines recommend use of morphine as a treatment of choice for pain relief in STEMI patients. However, this recommendation, although strong, is only based on expert consensus (class of recommendation I, level of evidence C). Morphine, apart from its analgesic effects, also alleviates the work of breathing and reduces anxiety. On the other hand, despite its favorable analgesic and sedative actions, morphine also exerts adverse effects, which include hypotension, bradycardia, respiratory depression, vomiting and reduction of gastrointestinal motility. Some of the previously listed morphine's side effects could affect the intestinal absorption and thus pharmacokinetics and pharmacodynamics of orally administered drugs which are concomitantly used with morphine. At present, no pharmacokinetic and pharmacodynamic data regarding the concurrent use of morphine and P2Y12 blockers in the STEMI or NSTEMI setting are available. Therefore, evidence-based verification of morphine's influence on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) could provide a valuable insight in the knowledge regarding modern acute myocardial infarction management.

Predefined subanalysis: aimed to investigate which one of platelet reactivity assessment methods utilized in the study (VASP assay, MEA, LTA, VerifyNow) best reflects concentration of ticagrelor and its active metabolite (AR-C124910XX).

Since there is no reference study examining pharmacokinetics of ticagrelor in STEMI or NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients for each arm) for estimating the final sample size.

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind Study Evaluating the Influence of Morphine on Pharmacokinetics and Pharmacodynamics of Ticagrelor and Its Active Metabolite (AR-C124910XX) in Patients With ST-segment Elevation Myocardial Infarction and Non-ST-segment Elevation Myocardial Infarction.
• Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Morphine morphine sulfate 5 mg IV followed by 180 mg loading dose of ticagrelor	Drug: Morphine; IV bolus injection; Other Names: Morphine sulfate ; Drug: Ticagrelor; 180 mg loading dose; Other Names: Brilique
Placebo Comparator: Placebo sodium chloride 0,9% 5 mg IV followed by 180 mg loading dose of ticagrelor	Drug: Placebo; IV bolus injection; Other Names: Sodium chloride 0,9% ; Drug: Ticagrelor; 180 mg loading dose; Other Names: Brilique

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-12h) [prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose]

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

Secondary Outcome Measures

1. Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-12h) [prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose]

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

2. Maximum Concentration of Ticagrelor [12 hours]

   Maximum concentration (Cmax) of ticagrelor

3. Maximum Concentration of AR-C124910XX [12 hours]

   Maximum concentration (Cmax) of AR-C124910XX

4. Time to Maximum Concentration for Ticagrelor [12 hours]

   Time to maximum concentration (Tmax) for ticagrelor

5. Time to Maximum Concentration for AR-C124910XX [12 hours]

   Time to maximum concentration (Tmax) for AR-C124910XX

6. Area Under the Plasma Concentration-time Curve for Ticagrelor (AUC 0-6h) [prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose]

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

7. Area Under the Plasma Concentration-time Curve for AR-C124910XX (AUC 0-6) [prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose]

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

8. Platelet Reactivity Index Assessed by VASP Assay [prior to the initial ticagrelor dose]

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

9. Platelet Reactivity Index Assessed by VASP Assay [30 minutes post ticagrelor dose]

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

10. Platelet Reactivity Index Assessed by VASP Assay [1 hour post ticagrelor dose]

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

11. Platelet Reactivity Index Assessed by VASP Assay [2 hours post ticagrelor dose]

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

12. Platelet Reactivity Index Assessed by VASP Assay [3 hours post ticagrelor dose]

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

13. Platelet Reactivity Index Assessed by VASP Assay [4 hours post ticagrelor dose]

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

14. Platelet Reactivity Index Assessed by VASP Assay [6 hours post ticagrelor dose]

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

15. Platelet Reactivity Index Assessed by VASP Assay [12 hours post ticagrelor dose]

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

16. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [prior to the initial ticagrelor dose]

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

17. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [30 minutes post ticagrelor dose]

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

18. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [1 hour post ticagrelor dose]

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

19. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [2 hours post ticagrelor dose]

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

20. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [3 hours post ticagrelor dose]

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

21. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [4 hours post ticagrelor dose]

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

22. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [6 hours post ticagrelor dose]

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

23. Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry [12 hours post ticagrelor dose]

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

24. P2Y12 Reaction Units Assessed by VerifyNow [prior to the initial ticagrelor dose]

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

25. P2Y12 Reaction Units Assessed by VerifyNow [30 minutes post ticagrelor dose]

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

26. P2Y12 Reaction Units Assessed by VerifyNow [1 hour post ticagrelor dose]

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

27. P2Y12 Reaction Units Assessed by VerifyNow [2 hours post ticagrelor dose]

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

28. P2Y12 Reaction Units Assessed by VerifyNow [3 hours post ticagrelor dose]

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

29. P2Y12 Reaction Units Assessed by VerifyNow [4 hours post ticagrelor dose]

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

30. P2Y12 Reaction Units Assessed by VerifyNow [6 hours post ticagrelor dose]

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

31. P2Y12 Reaction Units Assessed by VerifyNow [12 hours post ticagrelor dose]

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

32. Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP [2 hours]

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

33. Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With MEA [2 hours]

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

34. Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VerifyNow [2 hours]

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

35. Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VASP [12 hours]

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

36. Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA [12 hours]

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

37. Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow [12 hours]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• provision of informed consent prior to any study specific procedures

• diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction

• male or non-pregnant female, aged 18-80 years old

• provision of informed consent for angiography and PCI

Exclusion Criteria:

• chest pain described by the patient as unbearable or patient's request for analgesics

• prior morphine administration during the current STEMI or NSTEMI

• treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment

• hypersensitivity to ticagrelor

• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin

• active bleeding

• history of intracranial hemorrhage

• recent gastrointestinal bleeding (within 30 days)

• history of coagulation disorders

• platelet count less than <100 x10^3/mcl

• hemoglobin concentration less than 10.0 g/dl

• history of moderate or severe hepatic impairment

• history of major surgery or severe trauma (within 3 months)

• patients considered by the investigator to be at risk of bradycardic events

• second or third degree atrioventricular block during screening for eligibility

• history of asthma or severe chronic obstructive pulmonary disease

• patient required dialysis

• manifest infection or inflammatory state

• Killip class III or IV during screening for eligibility

• respiratory failure

• history of severe chronic heart failure (NYHA class III or IV)

• concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment

• body weight below 50 kg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology Department, Dr. A. Jurasz University Hospital	Bydgoszcz	Kujawsko-pomorskie	Poland	85-094

Sponsors and Collaborators

• Collegium Medicum w Bydgoszczy

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jacek Kubica, Prof. dr hab., Collegium Medicum w Bydgoszczy
• ClinicalTrials.gov Identifier: NCT02217878
• Other Study ID Numbers: CMUMK202
• First Posted: Aug 15, 2014
• Last Update Posted: Sep 12, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jacek Kubica, Prof. dr hab., Collegium Medicum w Bydgoszczy: ST-segment elevation myocardial infarction; non-ST-segment elevation myocardial infarction; ticagrelor; morphine; pharmacokinetics; pharmacodynamics; drug interactions; VASP assay; Multiple Electrode Aggregometry; VerifyNow
• Additional relevant MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction; Morphine; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Morphine	Placebo
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

Baseline Characteristics

Arm/Group Title	Morphine	Placebo	Total
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 Participants	35	35	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.7 (10.5)	62.5 (10.5)	61.5 (10.3)
Sex: Female, Male (Count of Participants)
Female	12 34.3%	7 20%	19 27.1%
Male	23 65.7%	28 80%	51 72.9%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.6 (4.3)	27.4 (4.0)	27.5 (4.2)
STEMI (participants) [Number]
Number [participants]	24 68.6%	21 60%	45 64.3%
GP IIb/IIIa administration (participants) [Number]
Number [participants]	10 28.6%	6 17.1%	16 22.9%
Hypertension (participants) [Number]
Number [participants]	15 42.9%	21 60%	36 51.4%
Diabetes mellitus (participants) [Number]
Number [participants]	8 22.9%	5 14.3%	13 18.6%
Dyslipidaemia (participants) [Number]
Number [participants]	30 85.7%	31 88.6%	61 87.1%
Current smoker (participants) [Number]
Number [participants]	17 48.6%	14 40%	31 44.3%
Prior AMI (participants) [Number]
Number [participants]	5 14.3%	8 22.9%	13 18.6%
Prior PCI (participants) [Number]
Number [participants]	4 11.4%	9 25.7%	13 18.6%
Prior CABG (participants) [Number]
Number [participants]	0 0%	0 0%	0 0%
Prior non-severe heart failure (participants) [Number]
Number [participants]	0 0%	3 8.6%	3 4.3%
Prior non-haemorrhagic stroke (participants) [Number]
Number [participants]	1 2.9%	0 0%	1 1.4%
Peripheral arterial disease (participants) [Number]
Number [participants]	3 8.6%	1 2.9%	4 5.7%
Chronic renal disease (participants) [Number]
Number [participants]	1 2.9%	2 5.7%	3 4.3%
Chronic obstructive pulmonary disease (participants) [Number]
Number [participants]	2 5.7%	0 0%	2 2.9%
Gout (participants) [Number]
Number [participants]	1 2.9%	2 5.7%	3 4.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Mean (Standard Deviation) [ng*h/mL]	6307 (4359)	9791 (5136)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Mean (Standard Deviation) [ng*h/mL]	1503 (1138)	2388 (1555)

3. Secondary Outcome

Title	Maximum Concentration of Ticagrelor
Description	Maximum concentration (Cmax) of ticagrelor
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Mean (Standard Deviation) [ng/mL]	1156 (771)	1683 (847)

4. Secondary Outcome

Title	Maximum Concentration of AR-C124910XX
Description	Maximum concentration (Cmax) of AR-C124910XX
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [ng/mL]	1085	1043

5. Secondary Outcome

Title	Time to Maximum Concentration for Ticagrelor
Description	Time to maximum concentration (Tmax) for ticagrelor
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [hours]	4	2

6. Secondary Outcome

Title	Time to Maximum Concentration for AR-C124910XX
Description	Time to maximum concentration (Tmax) for AR-C124910XX
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [hours]	4	4

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [ng*h/mL]	2491	5587

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [ng*h/mL]	472	1001

9. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	88.5	88.3

10. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	83.2	73.9

11. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	70.2	42.0

12. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	52.1	26.2

13. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	37.8	26.0

14. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	36.9	23.2

15. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	27.9	19.7

16. Secondary Outcome

Title	Platelet Reactivity Index Assessed by VASP Assay
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [Platelet Reactivity Index (%)]	27.5	15.6

17. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	85	77

18. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	86	48

19. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	59	23

20. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	31	23

21. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	35
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	27	17

22. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	29	13

23. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	19	11

24. Secondary Outcome

Title	Platelet Arbitrary Aggregation Units Assessed by Multiple Electrode Aggregometry
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

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [Platelet Arbitrary Aggregation Units]	19	11

25. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	232.5	238.5

26. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	30 minutes post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	268.5	210.5

27. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	1 hour post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	206.5	117.0

28. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	2 hours post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	137.0	44.0

29. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	3 hours post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	113.0	15.0

30. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	4 hours post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	50.5	9.0

31. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	6 hours post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	44.5	8.0

32. Secondary Outcome

Title	P2Y12 Reaction Units Assessed by VerifyNow
Description	P2Y12 Reaction Units (PRU) Assessed by VerifyNow (cut-off value for high platelet reactivity: PRU >208)
Time Frame	12 hours post ticagrelor dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [P2Y12 Reaction Units]	9.0	7.5

33. Secondary Outcome

Title	Percentage of Patients With High Platelet Reactivity After the Loading Dose of Ticagrelor Assessed With VASP
Description	Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VASP
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Number [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
Description	Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With MEA
Time Frame	2 hours

Outcome Measure Data

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
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
Measure Participants	25	29
Number [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
Description	Percentage of Patients With High Platelet Reactivity (HPR) After the Loading Dose of Ticagrelor Assessed With VerifyNow
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Number [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
Description	Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VASP
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Placebo
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
Measure Participants	35	35
Median (Inter-Quartile Range) [hours]	2.0	1

37. Secondary Outcome

Title	Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With MEA
Description	Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With MEA
Time Frame	12 hours

Outcome Measure Data

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
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
Measure Participants	25	29
Median (Inter-Quartile Range) [hours]	2.0	1.0

38. Secondary Outcome

Title	Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity Evaluated With VerifyNow
Description	Time to Reach Platelet Reactivity Below the Cut-off Value for High Platelet Reactivity (HPR) Evaluated With VerifyNow
Time Frame	12 hours

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Morphine	Placebo
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
Measure Participants	26	35
Median (Inter-Quartile Range) [hours]	1.0	0.5

Adverse Events

Time Frame	7 days
Arm/Group Title	Morphine		Placebo
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Morphine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/35 (2.9%)		2/35 (5.7%)
Cardiac disorders
Pulmonary oedema	0/35 (0%)		2/35 (5.7%)
Vascular disorders
Stent thrombosis	1/35 (2.9%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Morphine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/35 (14.3%)		7/35 (20%)
Cardiac disorders
Bradyarrhythmic event	1/35 (2.9%)		2/35 (5.7%)
Gastrointestinal disorders
Nausea	2/35 (5.7%)		0/35 (0%)
Vomiting	2/35 (5.7%)		0/35 (0%)
Vascular disorders
TIMI minor bleeding	0/35 (0%)		4/35 (11.4%)
TIMI minimal bleeding	0/35 (0%)		1/35 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

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.