Clinical trial NCT02422888: Reducing Micro Vascular Dysfunction in Acute Myocardial Infarction by Ticagrelor
Official title: Reducing Micro Vascular Dysfunction In Revascularized ST-elevation Myocardial Infarction Patients by Off-target Properties of Ticagrelor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: ST elevation myocardial infarction
Percutaneous coronary intervention
Endothelial function
Ticagrelor
Prasugrel
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: Hospital San Carlos, Madrid
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: University Medical Center Nijmegen
First posted: 2015-04-21
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current trial will compare the protective effect of ticagrelor and prasugrel on microvascular dysfunction in patients with revascularized ST elevation myocardial infarction.

Detailed description: Coronary microvascular dysfunction is highly prevalent in revascularized ST-elevation myocardial infarction and has important prognostic implications. Current data suggest that ticagrelor might be superior to prasugrel in the reduction of coronary microvasculature dysfunction. Thus, we have designed a clinical trial that will compare microvascular function in revascularized ST-elevation myocardial infarction patients at treatment steady state with ticagrelor or prasugrel. Coronary microvascular dysfunction will be assessed with the index of microcirculatory resistance after primary percutaneous coronary intervention and at 1 month follow-up in the infarct-related vessel and non-infarct related vessel.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Patients presenting with ST-elevation myocardial infarction \<12 hours after symptom onset
3. Successful percutaneous coronary intervention of the infarct-related vessel with a modern drug-eluting stent
4. Intermediate stenosis in non-infarct-related vessel (50-90%)

Exclusion Criteria:

1. history of myocardial infarction
2. Participation in another clinical study with an investigational product during the preceding 30 days
3. history of cerebrovascular accident (CVA) or 'transient ischaemic attack' (TIA)
4. History of intracranial haemorrhage
5. indication or use of oral anticoagulant therapy (i.e. acenocoumarol)
6. severe liver dysfunction (Child-Pugh score 10-15)
7. congestive heart failure
8. cardiogenic shock
9. left ventricular ejection fraction \< 35%
10. bleeding diathesis
11. age ≥ 75 or \< 18
12. body weight \< 60 kg
13. gout
14. coagulation disorders
15. severe pulmonary disease
16. pregnancy and breast feeding
17. limited life expectancy
18. platelet count \< 100 000/mm3
19. history of drug addiction or alcohol abuse in the past 2 years
20. need for chronic nonsteroidal anti-inflammatory drug
21. creatinine clearance \<30 mL/min or dialysis
22. chronic total occlusion (CTO)
23. Left main disease
24. allergy or contra-indication for ticagrelor or prasugrel
25. Contra-indication for adenosine
26. Patients unable to be followed on-site
27. Unable to undergo or contra-indications for MRI
28. Contra-indication for drug-eluting stent
29. Inability to obtain informed consent
30. Coronary artery bypass grafting in medical history

Primary outcomes:
measure: Index of microcirculatory resistance (IMR)
timeFrame: 1 month after primary PCI
Secondary outcomes:
measure: Delta Index of microcirculatory resistance (IMR)
timeFrame: Baseline vs. 1 month follow-up
measure: The reactive hyperemia index (RHI)
timeFrame: 1 month and 1 year after primary PCI
measure: Myocardial salvage
timeFrame: 1 month after primary PCI
measure: Left ventricular ejection fraction (LVEF) recovery
timeFrame: 1 month after primary PCI
measure: Microvascular obstruction
timeFrame: 3 days after primary PCI
measure: Asymmetric Dimethylarginine (ADMA) levels
timeFrame: 1 month after primary PCI
measure: Intra-myocardial haemorrhage
timeFrame: 3 days after primary PCI
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
state: Noord-Holland
Study officials:
References:
citation: van der Hoeven NW, Janssens GN, Everaars H, Nap A, Lemkes JS, de Waard GA, van de Ven PM, van Rossum AC, Escaned J, Mejia-Renteria H, Ten Cate TJF, Piek JJ, von Birgelen C, Valgimigli M, Diletti R, Riksen NP, Van Mieghem NM, Nijveldt R, van Leeuwen MAH, van Royen N. Platelet Inhibition, Endothelial Function, and Clinical Outcome in Patients Presenting With ST-Segment-Elevation Myocardial Infarction Randomized to Ticagrelor Versus Prasugrel Maintenance Therapy: Long-Term Follow-Up of the REDUCE-MVI Trial. J Am Heart Assoc. 2020 Mar 3;9(5):e014411. doi: 10.1161/JAHA.119.014411. Epub 2020 Mar 3.
citation: van Leeuwen MAH, van der Hoeven NW, Janssens GN, Everaars H, Nap A, Lemkes JS, de Waard GA, van de Ven PM, van Rossum AC, Ten Cate TJF, Piek JJ, von Birgelen C, Escaned J, Valgimigli M, Diletti R, Riksen NP, van Mieghem NM, Nijveldt R, van Royen N. Evaluation of Microvascular Injury in Revascularized Patients With ST-Segment-Elevation Myocardial Infarction Treated With Ticagrelor Versus Prasugrel. Circulation. 2019 Jan 29;139(5):636-646. doi: 10.1161/CIRCULATIONAHA.118.035931.
citation: Janssens GN, van Leeuwen MAH, van der Hoeven NW, de Waard GA, Nijveldt R, Diletti R, Zijlstra F, von Birgelen C, Escaned J, Valgimigli M, van Royen N. Reducing Microvascular Dysfunction in Revascularized Patients with ST-Elevation Myocardial Infarction by Off-Target Properties of Ticagrelor versus Prasugrel. Rationale and Design of the REDUCE-MVI Study. J Cardiovasc Transl Res. 2016 Jun;9(3):249-256. doi: 10.1007/s12265-016-9691-3. Epub 2016 Apr 21.