Acute Coronary SyndomePhase 4PLATE NOXNCT02169596
Is Efficacy of PLAtelet Aggregation Inhibition by Ticagrelor Mediated P2Y12 Blockade Dependent Upon Endogenous Endothelial Nitric OXide?
A Phase 4 study testing Ticagrelor and EndoPAT - endothelial assessment in people with Acute Coronary Syndome, run by Hull University Teaching Hospitals NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Acute Coronary Syndome
- What is being tested?
- Ticagrelor and EndoPAT - endothelial assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2015to Jul 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 41Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Castle Hill Hospital (Hull and east Yorkshire Hospitals NHS Trust)
Cottingham, East Yorkshire, HU16 5JQ
About this study
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?
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?
Read more
Aims
- Will ticagrelor increase the anti clot effect of vessel lining produced nitric oxide?
- 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.
- Conditions
- Acute Coronary Syndome
- Being tested
- Ticagrelor, EndoPAT - endothelial assessment
- Keywords
- Acute Coronary Syndrome, Nitric oxide, Ticagrelor, Antiplatelet agents, Endothelial function
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TicagrelorDrug
Also called blood test
Blood tests taken for flow cytometry
EndoPAT - endothelial assessmentOther
| Study group | Role | What they receive |
|---|---|---|
| Coronary Artery Disease | Other | Blood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD) Receives: 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) Receives: Drug: Ticagrelor; Other: EndoPAT - endothelial assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet Function
Direct testing with flow cytometry measuring fibrinogen binding, P-selectin, CD40L expression
Measured: up to 12 months (completion of study)
Secondary outcomes (1)
Reactive Hyperaemia Index
EndoPAT endothelial assessment
Measured: at 1 month, 6 months and at 12 months (completion of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2014 (estimated)
- Study startJun 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Coronary SyndomeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hull University Teaching Hospitals NHS Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02169596
- Sponsor's protocol ID
- PLATE NOX
- Other IDs
- 14/YH/0179
- Acronym
- PLATE NOX
- Status last verified
- Jul 2019
- First submitted
- 17 Jun 2014
- Last updated
- 15 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27127634
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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?
- ClinicalTrials.gov ID
- NCT02169596
- Acronym / sponsor ID
- PLATE NOX / PLATE NOX
- Conditions
- Acute Coronary Syndome
- Keywords
- Acute Coronary Syndrome, Nitric oxide, Ticagrelor, Antiplatelet agents, Endothelial function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Hull University Teaching Hospitals NHS TrustOther government
- Study start
- Jun 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 23 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Will ticagrelor increase the anti clot effect of vessel lining produced nitric oxide?
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Coronary Artery Disease | Other | Drug: Ticagrelor, Other: EndoPAT - endothelial assessmentBlood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD) |
| Healthy Normals | Other | Drug: Ticagrelor, Other: EndoPAT - endothelial assessmentBlood tests to assess platelet function and EndoPAT assessment for endothelial function testing before and after ticagrelor administration (90mg BD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (41 listed)
- Contra-indication to dual antiplatelet therapy
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TicagrelorAlso: blood testBlood tests taken for flow cytometry | Drug | Coronary Artery Disease, Healthy Normals |
| EndoPAT - endothelial assessment | Other | Coronary Artery Disease, Healthy Normals |
Primary outcome
Platelet Function
Time frame: up to 12 months (completion of study)
Direct testing with flow cytometry measuring fibrinogen binding, P-selectin, CD40L expression
1 secondary outcome
Reactive Hyperaemia Index
Time frame: at 1 month, 6 months and at 12 months (completion of study)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2019.
- Results publication: PubMed 27127634Rossington 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.
- Publication LinkLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ticagrelor and EndoPAT - endothelial assessment in people with Acute Coronary Syndome, run by Hull University Teaching Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet Function (time frame: up to 12 months (completion of study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02169596, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2019.