AFFECT EV: Antiplatelet Therapy Effect on Extracellular Vesicles in Acute Myocardial Infarction

• Sponsor: Medical University of Warsaw (Other)
• Overall Status: Completed
• CT.gov ID: NCT02931045
• Collaborator: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
• Enrollment: 60
• Locations: 2
• Arms: 2
• Actual Duration (Months): 24
• Patients Per Site: 30
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Platelet activation and aggregation leads to myocardial infarction. Platelet P2Y12 receptors are essential for platelet activation. Antagonists against the P2Y12 receptor, which are established in secondary prevention of myocardial infarction, have unexplained anti-inflammatory effects. A novel P2Y12 receptor antagonist ticagrelor reduced infection-related mortality compared to clopidogrel, previous standard treatment for patients with myocardial infarction. Activated platelets release pro-inflammatory and procoagulant platelet extracellular vesicles. The investigators assume that decrease in infection-related mortality in patients treated with ticagrelor may be explained by greater inhibition of the release of platelet vesicles by ticagrelor, compared to clopidogrel. This study is expected to identify an additional mechanism of action of ticagrelor, which might contribute to the observed clinical benefits in patients treated with ticagrelor.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: Ticagrelor; Drug: Clopidogrel	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Antiplatelet Therapy Effect on Platelet Extracellular Vesicles in Acute Myocardial Infarction
• Actual Study Start Date: Dec 30, 2017
• Actual Primary Completion Date: Dec 30, 2018
• Actual Study Completion Date: Dec 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ticagrelor Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose)	Drug: Ticagrelor; Comparison of ticagrelor with another antiplatelet drug (clopidogrel); Other Names: Brilique
Active Comparator: Clopidogrel Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose)	Drug: Clopidogrel; Comparison of clopidogrel with another antiplatelet drug (ticagrelor); Other Names: Plavix

Outcome Measures

Primary Outcome Measures

1. Concentration of Platelet Extracellular Vesicles/ml [6 months following the beginning of antiplatelet therapy]

   Concentration of platelet extracellular vesicles/ml measured with flow cytometry

Secondary Outcome Measures

1. Concentration of Extracellular Vesicles Exposing Fibrinogen [6 months]

   Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry

2. Concentration of Extracellular Vesicles Exposing Phosphatidylserine [6 months]

   Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry

3. Concentration of Extracellular Vesicles From Endothelial Cells [6 months]

   The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry

4. Concentration of Extracellular Vesicles From Leukocytes [6 months]

   Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age > 18 years

• Informed consent to participate in the study

• Percutaneous coronary intervention with stent implantation due to first S T elevation myocardial infarction, or first non S T -elevation myocardial infarction

• Administration of a loading dose of clopidogrel

Exclusion Criteria:

• Known coagulopathy

• Known history of bleeding disorder

• Suspicion of intracranial haemorrhage

• Need for oral anticoagulation therapy

• Administration of glycoprotein (GP) II b - III a antagonists

• Cardiogenic shock

• Severe chronic renal failure (estimated glomerular filtration rate < 30 mL/min)

• Severe liver insufficiency

• Chronic dyspnea

• Increased risk of bradycardia

• Autoimmune disease

• Infectious disease

• Neoplasms

• Pregnancy

• Study drug intolerance

• Co-administration of ticagrelor or clopidogrel with strong CYP3A4 inhibitors

• Participation in any previous study with ticagrelor or clopidogrel

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laboratory of Experimental Clinical Chemistry, Academic Medical Centre of the University of Amsterdam	Amsterdam		Netherlands
2	1st Chair and Department of Cardiology, Medical University of Warsaw	Warsaw		Poland

Sponsors and Collaborators

• Medical University of Warsaw
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

• Principal Investigator: Aleksandra Gasecka, MD, 1st Chair and Department of Cardiology, Medical University of Warsaw

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 21, 2016

More Information

Additional Information:

• Related Info

Publications

• Gasecka A, Nieuwland R, van der Pol E, Hajji N, Ćwiek A, Pluta K, Konwerski M, Filipiak KJ. P2Y12 antagonist ticagrelor inhibits the release of procoagulant extracellular vesicles from activated platelets. Cardiol J. 2019;26(6):782-789. doi: 10.5603/CJ.a2018.0045. Epub 2018 Apr 19.

• Responsible Party: Aleksandra Gasecka, Medical Doctor, Medical University of Warsaw
• ClinicalTrials.gov Identifier: NCT02931045
• Other Study ID Numbers: KB/112/2016
• First Posted: Oct 12, 2016
• Last Update Posted: Dec 23, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aleksandra Gasecka, Medical Doctor, Medical University of Warsaw: extracellular vesicles; inflammation; thrombosis; antiplatelet drugs
• Additional relevant MeSH terms: Myocardial Infarction; Infarction; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Ticagrelor	Clopidogrel
Arm/Group Description	Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose)	Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose)
Period Title: Overall Study
STARTED	30	30
COMPLETED	27	28
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Ticagrelor	Clopidogrel	Total
Arm/Group Description	Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose)	Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose)	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 63.3%	16 53.3%	35 58.3%
>=65 years	11 36.7%	14 46.7%	25 41.7%
Sex: Female, Male (Count of Participants)
Female	8 26.7%	6 20%	14 23.3%
Male	22 73.3%	24 80%	46 76.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Poland	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Concentration of Platelet Extracellular Vesicles/ml
Description	Concentration of platelet extracellular vesicles/ml measured with flow cytometry
Time Frame	6 months following the beginning of antiplatelet therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ticagrelor	Clopidogrel
Arm/Group Description	Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose) 27 patients	Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose) 28 patients
Measure Participants	27	28
Median (Inter-Quartile Range) [Platelet Extracellular Vesicles/mL]	2690000	4310000

2. Secondary Outcome

Title	Concentration of Extracellular Vesicles Exposing Fibrinogen
Description	Concentration of extracellular vesicles exposing fibrinogen/ ml measured with flow cytometry
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Concentration of Extracellular Vesicles Exposing Phosphatidylserine
Description	Concentration of extracellular vesicles exposing phosphatidylserine/ml measured with flow cytometry
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Concentration of Extracellular Vesicles From Endothelial Cells
Description	The concentrations of extracellular vesicles from endothelial cells/ ml measured with flow cytometry
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Concentration of Extracellular Vesicles From Leukocytes
Description	Concentration of extracellular vesicles from leukocytes/ ml measured with flow cytometry
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 months
Arm/Group Title	Ticagrelor		Clopidogrel
Arm/Group Description	Ticagrelor: oral, 180 mg once (loading dose) followed by 90 mg twice daily (maintenance dose) 27 patients One major bleeding event from the gynecologic tract		Clopidogrel: oral, 300 mg or 600 mg once (loading dose) followed by 75 mg once daily (maintenance dose) 28 patients One major bleeding event from a diabetic foot ulcer
All Cause Mortality
	Ticagrelor		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Ticagrelor		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		1/30 (3.3%)
Reproductive system and breast disorders
One major bleeding event from the gynecologic tract	1/30 (3.3%)	1	1/30 (3.3%)	1
Skin and subcutaneous tissue disorders
One major bleeding event from a diabetic foot ulcer	1/30 (3.3%)	1	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Ticagrelor		Clopidogrel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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