Prolonged Enoxaparin In Primary Percutaneous Coronary Intervention; A Pilot Pharmacodynamic Study
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- anti Xa activity change
Study Overview
Brief Summary
Heart attacks are caused by a clot blocking one or more of the heart arteries (coronary arteries). When complete blockage of one of the arteries occurs, emergency treatment to unblock the affected artery and rescue the heart muscle at risk is essential. This is usually achieved by performing an emergency procedure called primary percutaneous coronary intervention (PPCI).
Anticlotting treatment is also necessary to reduce the chances of further heart attacks. As part of standard care, tablets that target small cells called platelets (central to blood clot formation) are given as soon as an acute heart attack is suspected. These tablets include aspirin and ticagrelor/prasufrel. Although both ticgrelor and prasugrel are effective, the onset of action is delayed by up to 8 hours when given in context of an acute heart attack. This delay in onset of action can increase the risk of further heart attacks.
Enoxaparin is an anticlotting treatment that targets the other aspect of clot formation known as coagulation cascade. Enoxaparin or an alternative is recommended as a single does to support the PPCI procedure. The effects of a single shot of enoxaparin do not last long enough to bridge the gap in anticlotting treatment caused by the delayed action of ticagrelor/prasugrel. Since the investigators have realised the delayed onset of action of tablet therapy, the investigators have been using another drug called tirofiban as a drip. Tirofiban blocks platelets effectively, but greatly increases the risk of bleeding events.
The investigators believe that giving enoxaparin as a drip for 3-6 hours (following the single dose) instead of tirofiban, would be sufficient to bridge the gap in anticlotting effect without greatly increasing the risk of bleeding. This is a pilot study to assess the effects of enoxaparin drip in patients presenting with acute heart attacks and undergoing emergency treatment with PPCI.
Detailed Description
This is a single centre, pharmacodynamic pilot study of a prolonged enoxaparin infusion following the guideline directed bolus treatment in patients undergoing PPCI conducted at Sheffield Teaching Hospitals NHS Foundation Trust.
Patients admitted to the catheter laboratory or coronary care unit with STEMI and accepted for PPCI will be screened. Those meeting the inclusion criteria will be recruited following angiography. Aspirin is usually administered in the ambulance prior to patient's arrival to hospital and ticagrelor or prasugrel is given as soon as possible on arrival to hospital. This is part of standard clinical care.
The proposed anticoagulant intervention is a parenteral (intra-arterial or intravenous; IA/IV) bolus dose of enoxaparin (0.5 mg/kg) at the time of PPCI followed by an infusion of 0.5 mg/kg over a 6-hour period. In patients with impaired kidney function (eGFR < 30 ml/min), the infusion will be stopped at 3 hours (cumulative dose of 0.75 mg/kg).
Blood samples for anti Xa activity, VerifyNow P2Y12 assay and fibrin clot dynamics will be collected at the following time points:
- Time point 1 (T1) prior to anticoagulation - at the start of PCI procedure.
- Time point 2 (T2) at the end of PPCI.
- Time point 3 (T3) 2-3 hours from the start of enoxaparin infusion.
- Time point 4 (T4) at the end of enoxaparin infusion. In patients with impaired kidney function (eGFR < 30 ml/min), T3 will be the last blood sample taken (at the end of the infusion).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Confirmation of the diagnosis of STEMI by the clinical team on the basis of history, ECG changes and angiographic findings
- •Pre-treatment with either ticagrelor or prasugrel
- •Intention to proceed with PPCI
- •Feasibility to obtain informed verbal consent pre PPCI
Exclusion Criteria
- •Active bleeding that cannot be controlled by local measures
- •Female patients of child bearing age who have not had a sterilisation procedure
- •Patients with end stage renal failure requiring renal replacement therapy
- •Known thrombocytopenia (Platelet count < 100,000/μL)
- •Known history of intracranial haemorrhage
- •Known current treatment with oral anticoagulants
- •Known history of major surgery or trauma or history of GI/GU haemorrhage within the last month
- •Known intracranial malignancy or aneurysm
- •Known allergy to enoxaparin
- •Inability to easily understand verbal information given in English for any reason
- •Inability to give informed consent due to either temporary or permanent mental incapacity
Arms & Interventions
Enoxaparin
The patients will receive a 3-6 hour infusion of enoxaparin. The effects of the infusion will be assess when used on patients will acute heart attacks and undergoing emergency treatment with PPCI.
Intervention: Enoxaparin (Drug)
Outcomes
Primary Outcomes
anti Xa activity change
Time Frame: recruitment, baseline, 3 hrs from baseline, 6 hrs from baseline
To assess the pharmacodynamic effect of a prolonged enoxaparin infusion in the context.of PPCI. This will be achieved by serial measurements of anti Xa activity.
Secondary Outcomes
- P2Y12 Inhibition change(recruitment, baseline, 3 hrs from baseline, 6 hrs from baseline)
- Fibrin Clot Formation change(recruitment, baseline, 3 hrs from baseline, 6 hrs from baseline)
- Enoxaparin Regimen(within 12 hours from baseline)