Is Efficacy of PLAtelet Aggregation Inhibition by Ticagrelor Mediated P2Y12 Blockade Dependent Upon Endogenous Endothelial Nitric OXide? (PLATE NOX)

July 11, 2019 updated by: Hull University Teaching Hospitals NHS Trust

a Single Centre Open Pilot Study to Explore if the Efficacy of PLAtelet Aggregation Inhibition by Ticagrelor Mediated P2Y12 Blockade Dependent Upon Endogenous Endothelial Nitric OXide?

Background

Acute coronary syndrome (ACS) is a term representing all diseases related to reduction in blood flow to the heart characterised by clot formation over a segment of blood vessel narrowing. A major constituent of clot are blood cells called platelets and many of the medications used in ACS target platelet function. Ticagrelor is known to reduce platelet activity in clot formation by blocking a specific step in the process (P2Y12 receptors). A recent study has found that the presence of ticagrelor may also reduce clot formation by significantly enhancing another process involving the molecule nitric oxide (NO). This is of particular interest if translates into clinical practice, as many patients with heart disease have abnormal function of their blood vessel lining. This is known to cause a reduction in available nitric oxide. Does this therefore mean these patients will have a reduced response to ticagrelor therapy and subsequently be at increased risk of clot formation?

Aims

  1. Will ticagrelor increase the anti clot effect of vessel lining produced nitric oxide?
  2. Do patients with diabetes or smokers, who have poor function of their vessel lining, have a reduced response to ticagrelor?

Methods

This is a pilot study in which we propose to look at 64 patients with known disease of their heart blood vessels, with an equal mix of smokers, diabetics, smoking diabetics and non smoking non diabetics. We will also recruit ten healthy normal subjects to ensure that our tests produce the same results as the basic science study mentioned above.

To answer the questions posed we will perform blood tests, primarily looking at platelet function, and non-invasive blood vessel lining assessment. This will be done before and after ticagrelor treatment on each participant, enabling statistical comparison.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • East Yorkshire
      • Cottingham, East Yorkshire, United Kingdom, HU16 5JQ
        • Castle Hill Hospital (Hull and east Yorkshire Hospitals NHS Trust)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years
  • Coronary artery disease deemed to require Percutaneous Coronary Intervention
  • Diabetics must be established on oral or subcutaneous therapy
  • Non diabetics must have HbA1c levels between 20-42 mmol/mol
  • Current smokers are those that have smoked greater than 100 cigarettes and currently smoke on a daily basis
  • Non smokers have not smoked for greater than 3 years (and not on nicotine replacement)
  • Healthy controls are non smokers without medical history and taking no regular medication

Exclusion Criteria:

  • Contra-indication to dual antiplatelet therapy

    • Known bleeding disorders
    • Known malignant disease
    • Known myeloproliferative disease/malignant paraproteinaemia/heparin induced thrombocytopenia
    • Previous intracranial bleed
  • Already established on dual antiplatelet therapy
  • Known moderate-severe liver or splenic failure
  • Severe renal impairment
  • Major surgery due within one month of enrolment or before completion of measurements
  • Known allergy/intolerance to aspirin or ticagrelor
  • Reaction or side effect of aspirin or ticagrelor resulting in discontinuation prior to completion
  • Known allergy/intolerance to 3-hydroxy-3-methylglutaric acid Coenzyme A reductase inhibitor therapy (statins)
  • Concurrent use of high dose simvastatin/lovastatin (>40mg daily)
  • Currently taking medication that will interact with platelet function ie NSAIDS, antibiotics or herbal remedies
  • Concurrent use of strong cytochrome P450 3A4 inhibitors eg. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir
  • Concurrent use of strong cytochrome P450 3A4 inducers e.g. rifampicin, dexamethasone, phenytoin, carbamazepine and phenobarbital
  • Known sick sinus syndrome, second or third degree AV block or bradycardia-related syncope without permanent pacemaker in situ
  • Known severe asthma/Chronic Obstructive Pulmonary Disease or worsening of dyspnoeic symptoms on ticagrelor
  • Known severe gout
  • Currently taking calcium channel antagonist
  • Currently taking long acting nitrate
  • Currently taking >15mg/week of methotrexate
  • Women pregnant, breast feeding or of child bearing potential
  • Require anticoagulation on warfarin or Novel Oral AntiCoagulant
  • Platelet count <150 x109/L or >400 x109/L
  • Known blood bourne virus carrier
  • Unable to give informed consent
  • Involvement in a conflicting study
  • Non English speaker

Withdrawal Criteria following initial recruitment due to not meeting inclusion or exclusion criteria

  • Develop significant bleeding complications of medication requiring discontinuation of antiplatelet therapy prior to completion of the study
  • Urgent surgery undertaken during the study resulting in discontinuation of antiplatelet therapy prior to completion of the study
  • React or develop side effects of aspirin or ticagrelor resulting in discontinuation prior to completion of the study
  • Commence medication that will interact with platelet function before completion of the study
  • Commence use of strong cytochrome P450 3A4 inhibitors before completion of the study
  • Commence use of strong cytochrome P450 3A4 inducers before completion of the study
  • Worsening of dyspnoea in subjects with mild/moderate asthma/Chronic Obstructive Pulmonary Disease resulting in discontinuation of ticagrelor prior to completion of the study
  • Platelet count on initial sampling <150 x109/L or >400 x109/L
  • Non diabetic patients HbA1c level >42 mmol/mol
  • Noncompliance with medication
  • Subject wishes to no longer participate in the study (no reason or time period required)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Coronary Artery Disease
Blood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD)
Drug: Ticagrelor
Blood tests taken for flow cytometry
Other Names:
  • blood test
Other: EndoPAT - endothelial assessment
Other: Healthy Normals
Blood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD)
Drug: Ticagrelor
Blood tests taken for flow cytometry
Other Names:
  • blood test
Other: EndoPAT - endothelial assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet Function
Time Frame: up to 12 months (completion of study)
Direct testing with flow cytometry measuring fibrinogen binding, P-selectin, CD40L expression
up to 12 months (completion of study)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reactive Hyperaemia Index
Time Frame: at 1 month, 6 months and at 12 months (completion of study)
EndoPAT endothelial assessment
at 1 month, 6 months and at 12 months (completion of study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hull University Teaching Hospitals NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2015

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

June 17, 2014

First Submitted That Met QC Criteria

June 20, 2014

First Posted (Estimate)

June 23, 2014

Study Record Updates

Last Update Posted (Actual)

July 15, 2019

Last Update Submitted That Met QC Criteria

July 11, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PLATE NOX
  • 14/YH/0179 (Other Identifier: SouthYorks NRESCommittee.YorkandHumber- (HEALTH RESEARCH AUTHORITY))

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.

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