Clinical trial NCT01519518: How Effective Are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention
Official title: A Randomised Controlled Trial to Compare Unfractionated Heparin Versus Bivalirudin in the Treatment of Patients With a Clinical Diagnosis of ST-Segment Elevation Myocardial Infarction Events - For Planned Management With Primary PCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute ST Elevation Myocardial Infarction
Keywords: ST elevation myocardial infarction
Primary percutaneous coronary intervention
Unfractionated heparin
Bivalirudin
primary angioplasty
Lead sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
Sponsor class: OTHER
First posted: 2012-01-27
Enrollment: 1829
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare unfractionated heparin (UFH) and bivalirudin in the performance and subsequent outcomes of Primary percutaneous coronary intervention. This will be a pragmatic trial. Interventional procedures will be performed to reflect current and evolving standards, including predominant radial access. All patients will be treated with routine oral anti-platelet therapy pre-procedure. GP IIb/IIIa inhibitors will be reserved for 'bail out' treatment only.

Detailed description: HEAT-PPCI is a single-centre prospective, dual-arm, open-label, randomised controlled trial comparing two antithrombotic agents in patients undergoing PPCI. All patients presenting to the PPCI service at Liverpool Heart and Chest Hospital will be assessed for trial eligibility. The patients will be allocated by randomisation in equal proportions to the two treatment groups receiving UFH (70 units/kg prior to the procedure) or bivalirudin (bolus of 0.75 mg/kg prior to the start of the intervention, followed by an infusion of 1.75 mg/kg per hour for the duration of the procedure).

Pre-Specified Subgroup Analyses

* Subgroup analyses looking at the impact of access site comparing radial versus femoral route
* Assessment of the outcomes in diabetic patients receiving oral hypoglycaemic or insulin therapy versus all other patients
* Comparing the outcomes in patients \< or ≥ 75 years of age
* Type of p2y12 receptor inhibiting antiplatelet agent (Examples: clopidogrel, prasugrel, ticagrelor)
* Patients with impaired LV function versus normal LV function
* Patients managed with actual or attempted primary PCI versus no immediate PCI procedure attempted

PLATELET FUNCTION SUBSTUDY A substudy will be performed to assess indices of coagulation and platelet function studies comparing the impact of heparin or bivalirudin therapy on coagulation status at the end of the PPCI procedure. This study will be performed on all patients treated between the hours of 0800 and 1600, Monday to Friday. A single blood sample taken at the time of general blood sampling for routine clinical screening will be analysed.

Eligibility criteria: Inclusion Criteria:

* All patients presenting with a suspected myocardial infarction event with PPCI as the proposed index reperfusion strategy will be included in the trial

Exclusion Criteria:

* ≤ 18 years of age
* Known intolerance, hypersensitivity or contraindication to any trial medication
* Active bleeding at presentation
* Artificial ventilation, reduced conscious level or other factors precluding the administration of oral antiplatelet therapy
* Previous enrolment in this trial

Primary outcomes:
measure: Major Adverse Cardiac Events (MACE) in Terms of the Incidence of All Cause Mortality, Cerebrovascular Accident, Re-infarction and Additional Unplanned Target Lesion Revascularization
timeFrame: 28 days
measure: Type 3-5 Bleeding According to BARC (Bleeding Academic Research Consortium)Definition
timeFrame: 28 days
Secondary outcomes:
measure: CKMB Release Following Index Revascularisation Measured With a Single Estimation 12-18 Hours After the Procedure
timeFrame: 28 days
measure: Minor Bleeding: Type 2 Bleeding According to BARC (Bleeding Academic Research Consortium) Definition
timeFrame: 28 days
measure: Stent Thrombosis Rate (ARC Definite or Probable)
timeFrame: 28 days
measure: For Illustration, and to Allow Comparison With Existing Trials the Rate of Net Adverse Clinical Events (NACE), Combining the Primary Safety and Efficacy Outcomes
timeFrame: 28 days
measure: All Cause Mortality
timeFrame: 1 year
measure: Development of Thrombocytopenia
timeFrame: 28 days
measure: Door-to-first Device Time
timeFrame: 28 days
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital
state: Merseyside
Study officials:
affiliation: Liverpool Heart and Chest Hospital, Liverpool, UK
name: Rod Stables, MA DM FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R, Andron M, Appleby C, Fisher M, Khand A, Kunadian B, Mills JD, Morris JL, Morrison WL, Munir S, Palmer ND, Perry RA, Ramsdale DR, Velavan P, Stables RH; HEAT-PPCI trial investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014 Nov 22;384(9957):1849-1858. doi: 10.1016/S0140-6736(14)60924-7. Epub 2014 Jul 4.
citation: Malik N, Gershlick AH. The clinical and economic impact of bivalirudin for percutaneous coronary intervention. Expert Rev Pharmacoecon Outcomes Res. 2013 Dec;13(6):699-706. doi: 10.1586/14737167.2013.844650.