- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04174261
Ticagrelor in Remote Ischemic Preconditioning Study (TRIP)
Remote ischemic preconditioning (RIPC) reduces periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) through various pathways, including an adenosine-triggered pathway. Ticagrelor inhibits adenosine uptake, thus may potentiate the effects of RIPC.
This randomized trial tested the hypothesis that ticagrelor potentiates the effect of RIPC and reduces PMI, as assessed by post-procedural troponin release
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Percutaneous coronary intervention (PCI) is often complicated by peri-procedural myocardial injury, with widespread adoption of sensitive cardiac biomarkers assays allowing detection of smaller amounts of myocardial necrosis (1, 2). Peri-procedural cardiac troponin elevation has been associated with new irreversible myocardial injury, detected by delayed-enhancement magnetic resonance imaging (3), and even though the prognostic significance of peri-procedural cardiac troponin elevation has been highly debated (4), several studies have reported that peri-procedural injury is associated with worse prognosis (5, 6).
Peri-procedural myocardial injury attenuation is expected to improve cardiovascular outcomes following PCI, and this could be achieved through such cardioprotective interventions as ischemic preconditioning (IPC) (2). Converging experimental and clinical evidence suggests that the long-established therapeutic potential of remote IPC or ischemic perconditioning may find clinical use in the setting of elective PCI or ST-elevation myocardial infarction (MI)(7-9). Nevertheless, recent clinical trials suggest that the cardioprotective effect of remote IPC is moderate (10, 11), thus demonstrating the need to explore methods to augment it.
The ischemic conditioning signal is considered a summation of signals derived from multiple disparate receptor-ligand interactions, which reaches a threshold once sufficient combined signals are generated (12, 13). Adenosine, with its plasma levels increasing after cellular stresses and ischemia, is a crucial trigger of the preconditioning cascade (14), however it is rapidly taken up by cells through sodium-independent equilibrative nucleoside transporters (ENT 1/2) and sodium-dependent concentrative nucleoside transporters (CNT 2/3) (15).
Experimental data suggest that ticagrelor inhibits cellular reuptake of adenosine, thereby increasing systemic and tissue adenosine levels (15-17). Moreover, the antiplatelet effects of ticagrelor have been shown to be partly mediated by increased extracellular adenosine levels and ticagrelor enhances the hyperemic response to adenosine (16, 18). Clinical evidence suggests that in patients with acute coronary syndromes (ACS) ticagrelor treatment is associated with higher adenosine levels and an augmentation of coronary blood flow velocity in response to adenosine (19, 20). The investigators hypothesized that ticagrelor treatment would potentiate the effects of remote IPC and would thereby reduce peri-procedural myocardial injury and the incidence of post-PCI MI.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Attica
-
Athens, Attica, Greece, 11526
- Athens Red Cross Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provision of informed consent prior to any study specific procedures
- Patients (Female and male) ≥ 18 of age
- Patients with NSTE-ACS undergoing coronary angiography, eligible for PCI
Exclusion Criteria:
- Women of childbearing potential
- Severe comorbidity (estimated life expectancy <6 months)
- Baseline cTnI before PCI that is not stable or falling or is > 5 ×99th percentile URL.
- End-stage renal disease(eGFR<15 ml/min/1.73 m2)
- CRUSADE Bleeding Score >50
- Patients with an indication for oral anticoagulation
- On maintenance therapy with ticagrelor or those that have received clopidogrel for less than 3 days
- Use of nicorandil or glibenclamide
- Concomitant theophylline/aminophylline use
- Known contraindications to the use of ticagrelor Hypersensitivity to the active substance or to any of the excipients
- Active pathological bleeding
- History of intracranial haemorrhage
- Moderate to severe hepatic impairment
- Co-administration of ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir).
- Patients meeting criteria for immediate or early (<24h) invasive strategy based on the current relevant European Society of Cardiology guidelines
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Ticagrelor - Remote Ischemic Preconditioning
Ticagrelor 180mg loading dose, and 90mg b.i.d thereafter.
3 cycles of 5-minute ischemia/5-minute reperfusion using a BP cuff around the non-dominant arm
|
Preprocedural ticagrelor loading and standard dose thereafter
Preprocedural remote ischemic preconditioning on the non-dominant arm
|
OTHER: Ticagrelor - Control
Ticagrelor 180mg loading dose, and 90mg b.i.d thereafter.
BP-cuff uninflated around the non-dominant arm
|
Preprocedural ticagrelor loading and standard dose thereafter
|
ACTIVE_COMPARATOR: Clopidogrel - Remote Ischemic Preconditioning
Clopidogel 300mg loading dose, and 75mg q.d.
thereafter.
3 cycles of 5-minute ischemia/5-minute reperfusion using a BP cuff around the non-dominant arm
|
Preprocedural remote ischemic preconditioning on the non-dominant arm
Preprocedural clopidogrel loading and standard dose thereafter
|
OTHER: Clopidogrel - Control
Clopidogel 300mg loading dose, and 75mg q.d.
thereafter.
BP-cuff uninflated around the non-dominant arm
|
Preprocedural clopidogrel loading and standard dose thereafter
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
deltaTnI
Time Frame: At the time of PCI / 24 hours post-PCI
|
The primary outcome measure of the study was deltaTnI, defined as the difference between cardiac troponin I (cTnI) levels at 24 hours post-PCI and cTnI levels before the procedure.
|
At the time of PCI / 24 hours post-PCI
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Peri-procedural MI (type 4a MI)
Time Frame: 24 hours post-PCI
|
The prevalence of peri-procedural MI (type 4a MI) according to the third universal definition of MI (5xULN) was a secondary endpoint.
|
24 hours post-PCI
|
Chest pain during PCI: analog 10-point scale
Time Frame: During the PCI procedure
|
Chest pain during PCI was assessed at the post-PCI clinical examination of the subject by an appropriately qualified person, who was unaware of patient's treatment allocation.
An analog 10-point scale was used (0: no pain, 10: most severe discomfort ever experienced).
|
During the PCI procedure
|
ST-segment deviation during PCI
Time Frame: During the PCI procedure
|
ST-segment deviation during PCI was monitored by an appropriately qualified person, who was unaware of patient's treatment allocation.
It was defined as the absolute value of ST-segment deviation at 60-80ms after the J-point in mm at the beginning of coronary angiography minus ST-segment deviation at 60-80ms after the J-point in mm during balloon occlusion.
|
During the PCI procedure
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bleeding
Time Frame: At the time of PCI / 24 hours post-PCI
|
Bleeding, according to the Thrombolysis In Myocardial Infarction (TIMI) criteria, was considered as a safety outcome.
|
At the time of PCI / 24 hours post-PCI
|
Collaborators and Investigators
Investigators
- Principal Investigator: Apostolos Katsivas, Head Cardiology Department, Athens Red Cross Hospital
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Platelet Aggregation Inhibitors
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Ticagrelor
- Clopidogrel
Other Study ID Numbers
- ESR-14-10310
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Periprocedural Myocardial Infarction
-
Sohag UniversityNot yet recruitingPeriprocedural Myocardial Injury | Periprocedural Myocardial Infarction
-
University of Roma La SapienzaCompletedRosuvastatin in Preventing Myonecrosis in Elective Percutaneous Coronary Interventions (PCIs) (ROMA)Periprocedural Myocardial NecrosisItaly
-
Gennaro SardellaCompletedAssess the Periprocedural Myocardial NecrosisItaly
-
Fundación para la Investigación del Hospital Clínico...Completed
-
Shanghai Zhongshan HospitalUnknownCoronary Artery Disease | Percutaneous Coronary Intervention | Periprocedural Myocardial InjuryChina
-
Azienda ULSS 5 PolesanaUniversity of PadovaUnknownMyocardial Infarction, Acute | ST Segment Elevation Myocardial Infarction | Non-ST Elevation Myocardial Infarction (nSTEMI)Italy
-
University Medical Centre LjubljanaCompletedCardiac Arrest | Postresuscitation Syndrome | Myocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)Slovenia
-
Fundacio Privada Mon Clinic BarcelonaMiracor Medical SANot yet recruiting
-
Stiftung Institut fuer HerzinfarktforschungGlaxoSmithKline; University Hospital Muenster; Klinikum NürnbergCompletedMyocardial Infarction | ST-Elevation Myocardial Infarction | Non-ST-Elevation Myocardial InfarctionGermany
-
Population Health Research InstituteCanadian Institutes of Health Research (CIHR); Boston Scientific CorporationActive, not recruitingST Elevation Myocardial Infarction | Non ST Elevation Myocardial InfarctionCanada
Clinical Trials on Ticagrelor
-
Collegium Medicum w BydgoszczyCompleted
-
Federico II UniversityAdvicePharma GroupCompletedMyocardial Infarction | Coronary Artery Disease | Acute Coronary Syndrome | STEMI | NSTEMIItaly
-
University of FloridaCompleted
-
AstraZenecaParexelCompletedSickle Cell DiseaseGermany
-
University of FloridaAstraZenecaCompleted
-
University of FloridaThe Medicines CompanyCompletedCoronary Artery DiseaseUnited States
-
David AntoniucciAstraZeneca; A.R. CARD Onlus FoundationCompletedAcute Coronary Syndrome | Adverse Reaction to Antiplatelet AgentItaly, Greece
-
Centro Hospitalario La ConcepcionRecruiting
-
Sheba Medical CenterCompletedST Elevation Myocardial Infarction | Acute Coronary SyndromesIsrael
-
AstraZenecaCompletedMyocardial Infarction | Stroke | Atherothrombosis | Cardiovascular DeathSweden, United States, Australia, Brazil, Bulgaria, Czech Republic, France, Italy, Korea, Republic of, Peru, Poland, Russian Federation, South Africa, Spain, Turkey, United Kingdom, Germany, Philippines, China, Hungary, Romania, U... and more