Periprocedural Myocardial InfarctionPhase 4TRIPNCT04174261
Ticagrelor in Remote Ischemic Preconditioning Study
A Phase 4 study testing Ticagrelor, Remote Ischemic Preconditioning and Clopidogrel in people with Periprocedural Myocardial Infarction, run by Hellenic Society of Interventional Cardiology at 1 site in Greece.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Periprocedural Myocardial Infarction
- What is being tested?
- Ticagrelor, Remote Ischemic Preconditioning and Clopidogrel
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 245 participants
- Where
- 1 siteGreece
- Study dates
- 29 Jan 2017to 17 Jan 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Conditions
- Periprocedural Myocardial Infarction
- Being tested
- Ticagrelor, Remote Ischemic Preconditioning, Clopidogrel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Preprocedural ticagrelor loading and standard dose thereafter
Remote Ischemic PreconditioningProcedure or surgery
Preprocedural remote ischemic preconditioning on the non-dominant arm
ClopidogrelDrug
Preprocedural clopidogrel loading and standard dose thereafter
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor - Remote Ischemic Preconditioning | Experimental | 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 Receives: Drug: Ticagrelor; Procedure: Remote Ischemic Preconditioning |
| Ticagrelor - Control | Other | Ticagrelor 180mg loading dose, and 90mg b.i.d thereafter. BP-cuff uninflated around the non-dominant arm Receives: Drug: Ticagrelor |
| Clopidogrel - Remote Ischemic Preconditioning | Active comparator | 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 Receives: Procedure: Remote Ischemic Preconditioning; Drug: Clopidogrel |
| Clopidogrel - Control | Other | Clopidogel 300mg loading dose, and 75mg q.d. thereafter. BP-cuff uninflated around the non-dominant arm Receives: Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
deltaTnI
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.
Measured: At the time of PCI / 24 hours post-PCI
Secondary outcomes (3)
Peri-procedural MI (type 4a MI)
The prevalence of peri-procedural MI (type 4a MI) according to the third universal definition of MI (5xULN) was a secondary endpoint.
Measured: 24 hours post-PCI
Chest pain during PCI: analog 10-point scale
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).
Measured: During the PCI procedure
ST-segment deviation during PCI
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.
Measured: During the PCI procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start29 Jan 2017
- Primary completion18 Dec 2017
- Study completion17 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Periprocedural Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- The TRIP study was a randomized, assessor-blind, active comparator-controlled, clinical trial using a 2×2 factorial design, with 1:1 patient allocation to ticagrelor or clopidogrel and within each treatment a 1:1 allocation to RIPC or control.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 245 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hellenic Society of Interventional Cardiology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Apostolos Katsivas, Principal investigator, Head Cardiology Department, Athens Red Cross Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04174261
- Sponsor's protocol ID
- ESR-14-10310
- Acronym
- TRIP
- Status last verified
- Nov 2019
- First submitted
- 20 Nov 2019
- Last updated
- 22 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ticagrelor in Remote Ischemic Preconditioning Study
- ClinicalTrials.gov ID
- NCT04174261
- Acronym / sponsor ID
- TRIP / ESR-14-10310
- Conditions
- Periprocedural Myocardial Infarction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 245 participants (actual)
- Lead sponsor
- Hellenic Society of Interventional CardiologyUniversity, hospital or other
- Study start
- 29 Jan 2017 (actual)
- Primary completion
- 18 Dec 2017 (actual)
- Study completion
- 17 Jan 2018 (actual)
- First posted
- 22 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- The TRIP study was a randomized, assessor-blind, active comparator-controlled, clinical trial using a 2×2 factorial design, with 1:1 patient allocation to ticagrelor or clopidogrel and within each treatment a 1:1 allocation to RIPC or control.
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor - Remote Ischemic Preconditioning | Experimental | Drug: Ticagrelor, Procedure: Remote Ischemic PreconditioningTicagrelor 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 |
| Ticagrelor - Control | Other | Drug: TicagrelorTicagrelor 180mg loading dose, and 90mg b.i.d thereafter. BP-cuff uninflated around the non-dominant arm |
| Clopidogrel - Remote Ischemic Preconditioning | Active comparator | Procedure: Remote Ischemic Preconditioning, Drug: ClopidogrelClopidogel 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 |
| Clopidogrel - Control | Other | Drug: ClopidogrelClopidogel 300mg loading dose, and 75mg q.d. thereafter. BP-cuff uninflated around the non-dominant arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TicagrelorPreprocedural ticagrelor loading and standard dose thereafter | Drug | Ticagrelor - Control, Ticagrelor - Remote Ischemic Preconditioning |
| Remote Ischemic PreconditioningPreprocedural remote ischemic preconditioning on the non-dominant arm | Procedure or surgery | Clopidogrel - Remote Ischemic Preconditioning, Ticagrelor - Remote Ischemic Preconditioning |
| ClopidogrelPreprocedural clopidogrel loading and standard dose thereafter | Drug | Clopidogrel - Control, Clopidogrel - Remote Ischemic Preconditioning |
Primary outcome
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.
3 secondary outcomes
Peri-procedural MI (type 4a MI)
Time frame: 24 hours post-PCI
Chest pain during PCI: analog 10-point scale
Time frame: During the PCI procedure
ST-segment deviation during PCI
Time frame: During the PCI procedure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Apostolos Katsivas principal investigator
Head Cardiology Department, Athens Red Cross Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ticagrelor, Remote Ischemic Preconditioning and Clopidogrel in people with Periprocedural Myocardial Infarction, run by Hellenic Society of Interventional Cardiology at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
deltaTnI (time frame: At the time of PCI / 24 hours post-PCI). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.