NCT02701140

Brief Summary

The aim of this study is to assess the pleiotropic effects of ticagrelor that could represent possible mechanisms for its beneficial effects on cardiovascular mortality. We will test three different hypotheses:

  1. 1.Ticagrelor may increase ischemic preconditioning as compared to clopidogrel in patients with stable coronary disease, showing multivessel coronary artery disease and undergoing staged PCI.
  2. 2.Ticagrelor may improve microvascular perfusion in the myocardium of patients with multivessel coronary artery disease undergoing staged PCI.
  3. 3.Ticagrelor may exert positive effects enhancing the paracrine modulation, migration, homing and survival of hBMDSC, with a potential impact on the microvascular dysfunction and on the protective response to ischemia (cellular preconditioning).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
58

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 2, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 8, 2016

Completed
3 months until next milestone

Study Start

First participant enrolled

June 1, 2016

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2020

Completed
Last Updated

November 16, 2020

Status Verified

November 1, 2020

Enrollment Period

4.4 years

First QC Date

March 2, 2016

Last Update Submit

November 13, 2020

Conditions

Myocardial Ischemia

Outcome Measures

Primary Outcomes (1)

  • delta (difference) ST-segment elevation by intracoronary ECG

    Comparison of ticagrelor and clopidogrel on delta (difference) ST-segment elevation by intracoronary ECG during two-step sequential coronary balloon inflation in the culprit vessel

    within one hour

Secondary Outcomes (2)

  • CFR, IMR and FFR measured in the culprit vessel and reference vessel at the end of PCI

    within one hour

  • ticagrelor and clopidogrel on angina score

    within one hour

Study Arms (2)

Ticagrelor

ACTIVE COMPARATOR

Ticagrelor will be given in a loading dose of 180 mg followed by a dose of 90 mg twice daily.

Procedure: Coronary stentingProcedure: intracoronary ECG recordingProcedure: Coronary Flow reserveProcedure: Index of Microcirculatory ResistanceProcedure: Fractional Flow Reserve

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel will be given in a loading dose of 600 mg followed by a dose of 75 mg once a day.

Procedure: Coronary stentingProcedure: intracoronary ECG recordingProcedure: Coronary Flow reserveProcedure: Index of Microcirculatory ResistanceProcedure: Fractional Flow Reserve

Interventions

Coronary stentingPROCEDURE

Within 1h after the first PCI, patients will be randomized to either ticagrelor or clopidogrel.

ClopidogrelTicagrelor
intracoronary ECG recordingPROCEDURE

Measurement of ST segment elevation using intracoronary ECG recording

ClopidogrelTicagrelor
Coronary Flow reservePROCEDURE

measured with an intracoronary pressure/temperature sensor-tipped guidewire

Also known as: CFR
ClopidogrelTicagrelor
Index of Microcirculatory ResistancePROCEDURE

measured with an intracoronary pressure/temperature sensor-tipped guidewire

Also known as: IMR
ClopidogrelTicagrelor
Fractional Flow ReservePROCEDURE

measurement of Fractional Flow Reserve during hyperemic phase.

Also known as: FFR
ClopidogrelTicagrelor

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \> 18 and \< 75 years
  • Weight \> 60 Kg
  • Participants must have read and approved the informed consent and be compliant with the study procedures

You may not qualify if:

  • Pretreatment (before the first angiogram) with either prasugrel or ticagrelor. Patients initially treated with clopidogrel (including those who had a loading dose) will be enrolled.
  • Known hypersensitivity to aspirin, clopidogrel, ticagrelor or any excipients
  • Need for concomitant cardiac procedure, such as valve repair or replacement
  • Any previous history of ischemic stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm)
  • Any active pathological bleeding or history of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months, other bleeding diathesis, or considered by investigator to be at high risk for bleeding
  • Concomitant oral or IV therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices, (cyclosporine, quinidine), or strong CYP3A inducers (rifampin/rifampicin, phenytoin, carbamazepine).
  • Increased risk of bradycardia events
  • Known pregnancy, breast-feeding, or intend to become pregnant during the study period
  • Age \< 18 or ≥ 75 years
  • Severe uncontrolled chronic obstructive pulmonary disease
  • Concomitant theophylline/aminophylline use
  • Baseline ECG with infarct or conduction abnormalities (i.e. LVH with repolarization abnormality, bundle branch block, ST-segment abnormalities)
  • Evidence of prior myocardial infarction by cardiac imaging
  • Depressed left ventricular systolic function at randomization (ejection fraction \< 50% within 24 hours after first PCI)
  • Clinical congestive heart failure
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Catholic University of the Sacred Heart

Rome, 00168, Italy

Location

Related Publications (2)

  • D'Amario D, Galli M, Restivo A, Canonico F, Vergallo R, Migliaro S, Trani C, Burzotta F, Aurigemma C, Laborante R, Romagnoli E, Francese F, Ceccarelli I, Borovac JA, Angiolillo DJ, Tavazzi B, Leone AM, Crea F, Patti G, Porto I. Ticagrelor enhances the cardioprotective effects of ischemic preconditioning in stable patients undergoing percutaneous coronary intervention: the TAPER-S randomized study. Eur Heart J Cardiovasc Pharmacother. 2024 May 4;10(3):190-200. doi: 10.1093/ehjcvp/pvad092.

    PMID: 38006237DERIVED

  • D'Amario D, Restivo A, Leone AM, Vergallo R, Migliaro S, Canonico F, Galli M, Trani C, Burzotta F, Aurigemma C, Niccoli G, Buffon A, Montone RA, Flex A, Franceschi F, Tinelli G, Limbruno U, Francese F, Ceccarelli I, Borovac JA, Porto I, Crea F. Ticagrelor and preconditioning in patients with stable coronary artery disease (TAPER-S): a randomized pilot clinical trial. Trials. 2020 Feb 17;21(1):192. doi: 10.1186/s13063-020-4116-7.

    PMID: 32066489DERIVED

MeSH Terms

Conditions

Myocardial Ischemia

Interventions

Fractional Flow Reserve, Myocardial

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

Coronary CirculationBlood CirculationCardiovascular Physiological PhenomenaCirculatory and Respiratory Physiological Phenomena

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
PROBE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: PROBE
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

March 2, 2016

First Posted

March 8, 2016

Study Start

June 1, 2016

Primary Completion

November 1, 2020

Study Completion

November 1, 2020

Last Updated

November 16, 2020

Record last verified: 2020-11

Locations

IT(1)