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

NCT02169596 | Completed Phase 4 DMC

• 2 other identifiers: PLATE NOX14/YH/0179
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Coronary Syndome

Keywords

Acute Coronary Syndrome; Nitric oxide; Ticagrelor; Antiplatelet agents; Endothelial function

Outcome Measures

Primary Outcomes (1)

• Platelet Function

  Direct testing with flow cytometry measuring fibrinogen binding, P-selectin, CD40L expression

  up to 12 months (completion of study)

Secondary Outcomes (1)

• Reactive Hyperaemia Index

  at 1 month, 6 months and at 12 months (completion of study)

Study Arms (2)

Coronary Artery Disease

OTHER

Blood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD)

Drug: Ticagrelor; Other: EndoPAT - endothelial assessment

Healthy Normals

OTHER

Blood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD)

Drug: Ticagrelor; Other: EndoPAT - endothelial assessment

Interventions

Ticagrelor DRUG

Blood tests taken for flow cytometry

Also known as: blood test

Coronary Artery Disease; Healthy Normals

EndoPAT - endothelial assessment OTHER

Coronary Artery Disease; Healthy Normals

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hull University Teaching Hospitals NHS Trust: lead

Study Sites (1)

Castle Hill Hospital (Hull and east Yorkshire Hospitals NHS Trust)

Cottingham, East Yorkshire, HU16 5JQ, United Kingdom

Location

Related Publications (1)

• Rossington JA, Brown OI, Hoye A. Systematic review and meta-analysis of optimal P2Y12 blockade in dual antiplatelet therapy for patients with diabetes with acute coronary syndrome. Open Heart. 2016 Feb 26;3(1):e000296. doi: 10.1136/openhrt-2015-000296. eCollection 2016.

  PMID: 27127634 RESULT

Related Links

• Publication Link

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Ticagrelor; Hematologic Tests

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 23, 2014
• Study Start: June 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 15, 2019

Record last verified: 2019-07

Locations

GB (1)