Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02169596
Recruitment Status : Completed
First Posted : June 23, 2014
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Hull University Teaching Hospitals NHS Trust

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Acute Coronary Syndome Drug: Ticagrelor Other: EndoPAT - endothelial assessment Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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?
Study Start Date : June 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arm Intervention/treatment
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 Name: blood test

Other: EndoPAT - endothelial assessment
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 Name: blood test

Other: EndoPAT - endothelial assessment



Primary Outcome Measures :
  1. Platelet Function [ Time Frame: up to 12 months (completion of study) ]
    Direct testing with flow cytometry measuring fibrinogen binding, P-selectin, CD40L expression


Secondary Outcome Measures :
  1. Reactive Hyperaemia Index [ Time Frame: at 1 month, 6 months and at 12 months (completion of study) ]
    EndoPAT endothelial assessment



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

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): NCT02169596


Locations
Layout table for location information
United Kingdom
Castle Hill Hospital (Hull and east Yorkshire Hospitals NHS Trust)
Cottingham, East Yorkshire, United Kingdom, HU16 5JQ
Sponsors and Collaborators
Hull University Teaching Hospitals NHS Trust
Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: Hull University Teaching Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT02169596    
Other Study ID Numbers: PLATE NOX
14/YH/0179 ( Other Identifier: SouthYorks NRESCommittee.YorkandHumber- (HEALTH RESEARCH AUTHORITY) )
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019
Keywords provided by Hull University Teaching Hospitals NHS Trust:
Acute Coronary Syndrome
Nitric oxide
Ticagrelor
Antiplatelet agents
Endothelial function
Additional relevant MeSH terms:
Layout table for MeSH terms
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs