Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

TIMES: Ticagrelor vs. Placebo/ Clopidogrel With Aspirin in Anterior STEMI Patients Treated With Primary PCI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03145194
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Papworth Hospital NHS Foundation Trust

Brief Summary:
This is a single-centred, double blind randomized controlled trial comparing ticagrelor with placebo in clopidogrel and aspirin loaded patients.

Condition or disease Intervention/treatment Phase
ST Elevation Myocardial Infarction Drug: Ticagrelor Other: Placebo Phase 2

Detailed Description:

The very early benefit of ticagrelor in STEMI is co-mediated by adenosine cardioprotection maintaining/ improving myocardial microcirculatory function, as well as via platelet inhibition or possibly other pleiotropic effects.

Ticagrelor increases circulating adenosine by reducing cellular re-uptake. Adenosine is a cardioprotective agent that utilizes cellular survival kinase pathways that may have beneficial effects on the microcirculation and myocardium in patients presenting with STEMI. Adenosine is currently used as a treatment for no-reflow and improves MVO post-STEMI when administered during PPCI. A recent study of healthy volunteers has confirmed that non-invasive coronary flow is augmented by ticagrelor and that this is mediated by adenosine. The Investigators propose that the very early beneficial effects of Ticagrelor in ACS may be adenosine mediated cardioprotection, rather than only due to an antiplatelet effect. This important research is original and a natural progression of the ticagrelor story. It expands the adenosine hypothesis and mode of action of ticagrelor and addresses a novel cardioprotective/ microcirculatory mechanism of action.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double blind until the point of primary endpoint.
Primary Purpose: Treatment
Official Title: A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) With Aspirin in Patients Presenting With Anterior STEMI Treated With Primary PCI
Actual Study Start Date : January 30, 2017
Estimated Primary Completion Date : November 30, 2018
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ticagrelor
Patients will receive Ticagrelor 180mg (2 x 90mg tablets)
Drug: Ticagrelor
2 x 90mg Ticagrelor tablets

Placebo Comparator: Placebo
Patients will receive Placebo (2 matching tablets)
Other: Placebo
2 x matching placebo tablets




Primary Outcome Measures :
  1. Index of Myocardial Resistance (IMR) [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare final Index of Myocardial Resistance (IMR) at the end of the PPCI procedure between the two arms.


Secondary Outcome Measures :
  1. Baseline IMR and change in IMR during PPCI [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare between the two arms.

  2. ACF and AMR pre/post PPCI [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare between the two arms.

  3. TIMI flow and TMBG pre/post PPCI [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare between the two arms.

  4. ST segment resolution [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare between the two arms.

  5. OCT quantified clot volume pre/post PPCI [ Time Frame: Baseline to end of PPCI procedure. ]
    To compare between the two arms.

  6. Cardiac troponin - I and CKMB levels at 0, 12 and 24 hours [ Time Frame: Baseline to 24 hours. ]
    To compare between the two arms.

  7. Cardiac MRI microvascular obstruction between 24-48 hours and infarct size at 3 months [ Time Frame: Baseline to 3 months. ]
    To compare between the two arms.


Other Outcome Measures:
  1. Creatinine levels (eGRF) at 0, 12 and 24 hours [ Time Frame: Baseline to 24 hours. ]
    Safety endpoint.

  2. NYHA Functional Classification and CCS Angina Grading Scale [ Time Frame: Discharge to 12 months. ]
    Clinical grading scales of heart failure and angina.

  3. Plasma Ticagrelor levels at the point of final IMR measurement and in-patient Cardiac MRI. [ Time Frame: End of PPCI procedure to 24-48 hours. ]
    This will explore if the IMR differences observed are related to individual differences in drug levels.

  4. Plasma Adenosine levels at the point of final IMR measurement and in-patient Cardiac MRI [ Time Frame: End of PPCI procedure to 24-48 hours. ]
    This will explore if the IMR differences observed are related to individual differences in adenosine levels.

  5. Multiplatelet® ADP aggregation assessment of platelet reactivity at the point of final IMR measurement and in-patient Cardiac MRI [ Time Frame: End of PPCI procedure to 24-48 hours. ]
    This will explore if the IMR differences observed are related to individual differences in platelet reactivity levels.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed verbal consent prior to any study specific procedures taking place with written consent confirmed prior to in-patient cardiac MRI.
  2. Male or female adult patient aged 18 - 90 years old
  3. Anterior STEMI (ST elevation ≥ 2mmHg in contiguous chest leads) with chest pain symptom onset < 12 hours

Exclusion Criteria:

  1. Cardiogenic shock*
  2. Previous anterior myocardial infarction
  3. Unfavourable coronary anatomy for PCI: left main / surgical or distal coronary disease
  4. Already prescribed Ticagrelor at the time of admission
  5. Factors affecting study drug administration/ absorption: vomiting or allergy
  6. Concomitant use of potent CYP3A4 inhibitors/ inducers (e.g ketoconazole and rifampicin) or CYP3A4 substrates with a narrow therapeutic window (e.g. cisapride and ergot alkaloids) or simvastatin / lovostatin >40mg oral dose.
  7. Severe bleeding diathesis or current active bleeding*
  8. History of intracranial haemorrhage
  9. Moderate or Severe hepatic impairment
  10. Severe asthma or bradycardia/ complete heart block (contraindications to adenosine)*
  11. Severe co-morbidity with a life expectancy < 3 months.
  12. Women of child bearing potential (as determined by direct questioning of the patient to confirm and this will be documented in the medical notes).

    • Patients that are found to have any excluding factor (e.g., unfavourable coronary anatomy for PCI) or develop any excluding factor (e.g., vomiting or cardiogenic shock) before the point of final IMR assessment will be discontinued from the study and followed up at discharge and by telephone at 3 and 12 months for adverse event monitoring purposes only.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03145194


Contacts
Layout table for location contacts
Contact: Stephen Hoole 01480 366172 ext 6172 s.hoole@nhs.net

Locations
Layout table for location information
United Kingdom
Papworth Hospital NHS Foundation Trust Recruiting
Papworth Everard, Cambridge, United Kingdom, CB23 3RE
Contact: Stephen Hoole    01480 366172 ext 6172    s.hoole@nhs.net   
Principal Investigator: Stephen Hoole         
Sponsors and Collaborators
Papworth Hospital NHS Foundation Trust
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Stephen Hoole Papworth Hospital NHS Foundation Trust

Layout table for additonal information
Responsible Party: Papworth Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03145194     History of Changes
Other Study ID Numbers: P01910
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Myocardial Infarction
ST Elevation Myocardial Infarction
Myocardial Ischemia
Infarction
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Aspirin
Clopidogrel
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists