Bivalirudin in Late PCI for Oatients With STEMI

Phase 4

• Conditions: STEMI - ST Elevation Myocardial Infarction
• Interventions: Drug: Bivalirudin; Drug: Heparin

• Registration Number: NCT04185077
• Lead Sponsor: Second Xiangya Hospital of Central South University

Brief Summary

Bivalirudin is recomended by guidelines during primary PCI procedure for patients with STEMI. However, there is a large number of STEMI patients who missed the primary PCI. So the investigators aim to study the efficiency and safety of bivalirudin as the anticoagulation therapy during late PCI.

Detailed Description

Antithrombotic therapy is essential to prevent adverse ischemic events, especially stent thrombosis and reinfarction during and after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Bivalirudin is emerging as an alternative for heparin during PCI procedure1.

Bivalirudin (BIV) a synthetic, bivalent, 20-amino acid direct thrombin inhibitor, was found to have the advantages of inhibiting fibrin-bound thrombin, a predictable effect of anticoagulation, and a short half-life of approximately 30 minutes in humans with normal renal function. BIV has been introduced in percutaneous coronary interventions (PCIs) especially for patients with ACS. Compared with heparin, series clinical trials indicated that BIV was not inferior to UFH as a procedural anticoagulant and there was no increased bleeding.

In the real world, there are as many as 47.1% patients with STEMI can not get early reperfusion therapy. Huge number of patients missed the best time window for PCI. For these patients, the usual PCI procedure are usually performed 1-2 weeks after attack, which is called late PCI.

For patients with STEMI, Bivalirudin is recomended by guidelines in ESC during PCI procedure. However, the evidences (ACUITY，HORIZONS-AMI，EUROMAX, EAT-PPCI，BRIGHT, VALIDATE-SWEDEHEART) supporting the guideline nearly all comes from primary PCI for STEMI, which means there has no clinical trials focus on late PCI for patients with STEMI yet.

Clinically, late PCI, defined as the time to open an infarct-related artery (IRA) from symptoms onset \> 7 days (when the myocardial condition is considered stable), is practiced commonly for these late presenters. Whether late PCI is adequately beneficial is controversial. Currently, heparin is applied during late PCI as the anticoagulation therapy, it is still unknown of the efficiency and safety for bivalirudin as the anticoagulation therapy during late PCI.

So in this RCTs, the investigators aim to study the efficiency and safety of bivalirudin as the anticoagulation therapy during late PCI.

Study Timeline

• Study First Submitted: 2019-11-29
• Study First Submitted QC: 2019-11-29
• Study Start: 2019-11-30
• Status Verified: 2019-12
• Study First Posted: 2019-12-04
• Last Update Submitted: 2019-12-06
• Last Update Posted: 2019-12-10
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

1. Patients aged over 18 years.
2. Patients with ST-segment elevation MI (STEMI) undergoing late PCI 24 hours to 2 weeks after symptom onset. STEMI was defined as ST-segment elevation ≥0.1 mV in ≥2 contiguous leads or documented newly developed left bundle branch block.
3. Patients with develop Q-waves at presentation and with clear culprit vessel confirmed by angiography or other clinical evidences.
4. No any other anticoagulation therapy 12 hours before late PCI.

Exclusion Criteria

• STEMI patients undergoing primary PCI in 24 hours after symptom attack; patient unwilling or unable to provide written informed consent. thrombolytic therapy administered before randomization; any condition making PCI unsuitable or that might interfere with study adherence;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	Bivalirudin	Bivalirudin (Salubris Pharmaceuticals Co) was given as a bolus of 0.75mg/kg followed by infusion of 1.75mg/kg/h during the PCI procedure and for at least 30 minutes but no more than 4 hours afterwards. Following this mandatory infusion, a reduced-dose infusion (0.2mg/kg/h) for up to 20 hours could be administered at physician discretion. An additional bivalirudin bolus of0.3mg/kgwasgivenif the activatedclotting time 5minutes after the initial bolus (measuredwith the Hemotec assay) was less than 225 seconds.
Control	Heparin	a bolus dose of 100 U/kg Heparin was administered according to current guidelines.Additional heparinwasadministered if the post-bolus activated clotting time was less than 225 seconds.

Primary Outcome Measures

Name	Time	Method
Rate of net adverse clinical events	30 days after discharge	a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or any bleeding as defined by the Bleeding Academic Research Consortium(BARC) definition (grades 1-5).

Secondary Outcome Measures

Name	Time	Method
Rate of major adverse cardiac or cerebral events	30 days after enrollment	all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke
Rate of any bleeding	30 days after enrollment	Bleeding was considered medically actionable if BARC types 2 through 5 and was considered major if BARC types 3 through 5 occurred.
Rate of stent thrombosis	30 days after enrollment	according to the Academic Research Consortium criteria
Rate of acquired thrombocytopenia	30 days after enrollment	defined as a platelet count decrease ofmore than50%or more than 150 × 109/L frombaseline