Clinical trial NCT03568838: Prolonged Enoxaparin in Primary Percutaneous Coronary Intervention
Official title: Prolonged Enoxaparin in Primary Percutaneous Coronary Intervention Compared With Standard of Care Therapy - The PENNYWISE Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Medical Research Council
First posted: 2018-06-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomised (1:1) using an opaque sealed envelope methodology prior to coronary angiography.

Patients allocated to the experimental arm will receive a parenteral (IA/IV) bolus dose of enoxaparin (0.75 mg/kg) pre PPCI followed by an infusion of 0.75 mg/kg over a 6-hour period to be started as soon as possible when PPCI starts.

Patients randomised to the standard therapy arm will receive treatment as guided by the treating cardiologist in line with the local standard-of-care, usually consisting of UFH and a GPI.
Primary purpose: PREVENTION

Brief summary: This is a feasibility study aiming to generate pilot data on safety and efficacy of a novel anticoagulant regimen (enoxaparin bolus and prolonged infusion) compared to the local standard-of-care in opiate-treated patients undergoing primary percutaneous coronary intervention.

Detailed description: Delayed absorption of oral P2Y12 inhibitors in patients undergoing primary percutaneous coronary intervention (PPCI) may increase the risk of stent thrombosis. Parenteral treatment is needed mitigate this risk.

We have recently shown a novel regimen of enoxaparin (bolus 0.75 mg/kg followed by an infusion of 0.75 mg/kg/6h) to provide consistent antithrombotic effects until the end of the infusion (1). We have also demonstrated the high prevalence of delayed platelet inhibition in opiate-treated patients (1).

This is a feasibility study for a larger randomised controlled trial (RCT). We aim to assess recruitment rate and collect pilot data on safety and efficacy. This will be a single-centre, open-label RCT comparing this novel regimen of enoxaparin to the local standard-of-care which usually consists of unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. The study population will be opiate-treated patients undergoing PPCI. Pre PPCI, patients will be allocated in 1:1 ratio using a simple randomisation method using sealed envelopes, to either enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg infusion over 6 hours (n=50) or the standard-of-care of UFH and tirofiban (n=50).

Eligibility criteria: Inclusion Criteria:

* Age \>18
* Confirmation of the diagnosis of STEMI by the clinical team on the basis of history and ECG changes
* Intention to proceed with PPCI
* Treated with opiates for analgesia
* Feasibility to obtain informed verbal consent pre PPCI

Exclusion Criteria:

* Active bleeding that cannot be controlled by local measures
* Pregnant patients
* Patients with end-stage renal failure requiring renal replacement therapy
* Patients with cardiogenetic shock
* Known thrombocytopenia (Platelet count \<100,000)
* 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
* known hypersensitivity to benzylalcohol
* Patients with known acute bacterial endocarditis
* Known active gastric or duodenal ulceration
* 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
* Current participation, or participation within the last month, in an interventional clinical trial.

Primary outcomes:
measure: Recruitment Rate
timeFrame: Through study completion, average 1 year
measure: Bleeding rates within 24 hours
timeFrame: Through study completion, average 1 year
Secondary outcomes:
measure: Acute stent thrombosis rate in each treatment arm
timeFrame: Through study completion, average 1 year
measure: Rates of ST-segment resolution in each treatment arm
timeFrame: Through study completion, average 1 year
measure: Rates of the composite outcomes
timeFrame: Through study completion, average 1 year
measure: 1-year mortality rates
timeFrame: Through study completion, average 1 year
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
state: South Yorkshire
Study officials:
affiliation: Sheffield Teaching Hospitals NHS FT
name: Robert Storey
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sumaya W, Parker WAE, Fretwell R, Hall IR, Barmby DS, Richardson JD, Iqbal J, Adam Z, Morgan KP, Gunn JP, Mason AE, Judge HM, Gale CP, Ajjan RA, Storey RF. Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study). Thromb Haemost. 2018 Jul;118(7):1250-1256. doi: 10.1055/s-0038-1657768. Epub 2018 Jun 6.