EARLY Routine Catheterization After Alteplase Fibrinolysis vs. PPCI in ST-Segment-Elevation MYOcardial Infarction

Phase 4

Completed

• Conditions: Acute ST-segment Elevation Myocardial Infarction
• Interventions: Procedure: Primary PCI; Drug: Alteplase; Procedure: Early post-fibrinolytic catheterisation

• Registration Number: NCT01930682
• Lead Sponsor: RenJi Hospital

Brief Summary

The EARLY-MYO (EARLY routine catheterization after alteplase fibrinolysis vs. primary PCI in acute ST-segment elevation MYOcardial infarction) is an investigator-initiated, prospective, multicenter, randomized (1:1), open-label, actively-controlled, parallel group, non-inferiority trial comparing the efficacy and safety of a PhI strategy with half-dose fibrinolysis versus PPCI in STEMI patients presenting within 6 hours after symptom onset and with an expected PCI-related delay of ≥60 min.

Detailed Description

Early, successful restoration of myocardial perfusion after a ST-elevation myocardial infarction (STEMI) is the most effective way to reduce final infarct size and improve clinical outcome. Reperfusion for STEMI treatment in the modern era encompasses mechanical and pharmacological strategies. It is generally well-accepted that primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for all STEMI patients when it can be performed within the guideline-recommended timeframe at PPCI-capable facilities. However, PPCI is not universally available, and delays in performing percutaneous coronary intervention (PCI) are common in real-world practice. Even in some large cities, patients have a high chance of presenting to hospitals not providing around-the-clock PPCI service. Given this background, in recent years there has been great interest and progress in creating triage strategies for STEMI patients who cannot receive timely PPCI.

Pharmaco-invasive (PhI) strategy, an early reperfusion strategy by initial prompt fibrinolysis with subsequent early catheterization (with either routine early PCI after successful fibrinolysis or rescue PCI as needed), has been proposed as a therapeutic option for STEMI patients when timely PPCI is not feasible. However, current evidence on the efficacy and safety of PhI strategy in STEMI patients is limited, and the role of PhI strategy in STEMI continues to be debated. Given that no randomized clinical trial is available to compare a PhI strategy with half-dose fibrinolytic regimen versus PPCI in STEMI patients, investigators plan to perform a controlled, randomized trial to evaluate the efficacy and safety of a PhI strategy with half-dose alteplase fibrinolysis versus PPCI in STEMI patients.

Study Timeline

• Status Verified: 2013-08
• Study First Submitted: 2013-08-19
• Study First Submitted QC: 2013-08-25
• Study First Posted: 2013-08-29
• Study Start: 2014-01-13
• Primary Completion: 2016-09
• Study Completion: 2016-09-12
• Last Update Submitted: 2017-08-28
• Last Update Posted: 2017-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 344

Inclusion Criteria

• Age: over 18 or 18 years old, less than 75 years old;
• Patents with myocardial infarction who have symptom onset within 6h before randomization;
• ECG: ≥2 mm ST-segment elevation in 2 contiguous precordial leads or ≥1 mm ST-segment elevation in 2 contiguous extremity leads ;
• Patents with an expected PCI-related delay [expected time delay from FMC to first balloon dilation≥90 min, and difference between the time of FMC to balloon dilation minus the time from FMC to start of fibrinolysis ≥60 minutes)];
• Signed informed consent form prior to trial participation.

Exclusion Criteria

1. Evidence of cardiac rupture;

2. ECG: new left bundle branch block;

3. "Diagnosis to balloon inflation" time over 3 hours;

4. Thrombolysis contradictions:

   • Definite cerebral apoplexy history;
   • Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) or recent trauma to the head or cranium (i.e. < 3 months);
   • Active bleeding or known bleeding disorder/diathesis;
   • Recent administration of any i.v. or s.c. anticoagulation within 12 hours including unfractionated heparin, enoxaparin and/or bivalirudin or current use of oral anticoagulation(warfarin or coumadin);
   • Uncontrolled hypertension, defined as a single blood pressure measurement ≥ 180/110 mm Hg (systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg) prior to randomisation;
   • Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with the current myocardial infarction); Prolonged or traumatic cardiopulmonary resuscitation (> 10 minutes) within the past 2 Weeks Major surgery pending in the following 30 days;

5. Severe complication

   • Other diseases with life expectancy ≤12 months;
   • Any history of Severe renal or hepatic dysfunction(hepatic failure, cirrhosis, portal hypertension and active hepatitis); Neutropenia, thrombocytopenia ; Known acute pancreatitis;
   • Known acute pericarditis and/or subacute bacterial endocarditis;
   • Arterial aneurysm, arterial/venous malformation and aorta dissection;

6. Complex heart condition

   • Cardiogenic shock(SBP <90 mmHg after fluid infusion or SBP<100 mmHg after vasoactive drugs);
   • PCI within previous 1 month or Previous coronary-artery bypass surgery(CABG);
   • Previously known multivessel coronary artery disease not suitable for revascularization;
   • Hospitalisation for cardiac reason within past 48 hours;

7. Not suitable for clinical trial

   • Inclusion in another clinical trial;
   • Previous enrolment in this study or treatment with an investigational drug or device under another study protocol in the past 7 days;
   • Pregnancy or lactating;
   • Body weight <40kg or >125kg;
   • Known hypersensitivity to any drug that may appear in the study;
   • Inability to follow the protocol and comply with follow-up requirements or any other reason that the investigator feels would place the patient at increased risk.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early post-fibrinolytic catheterisation	Early post-fibrinolytic catheterisation	For STEMI Patients, alteplase is given as a intravenous bolus (8-mg) followed by 42 mg iv gtt in 90 min.Early routine catheterization after 3 hours but within 24 hours of the start of fibrinolytic therapy is performed, if required, PCI or, in case of insufficient ST resolution at 90 min,rescue PCI. The decision on rescue PCI will, however, be taken 90 min (or earlier if clinically indicated) after injection of alteplase according to the ST resolution (less than 50% reduction in ST-segment elevation).
Primary PCI	Primary PCI	For STEMI Patients,primary PCI is performed without fibrinolytic therapy.
Early post-fibrinolytic catheterisation	Alteplase	For STEMI Patients, alteplase is given as a intravenous bolus (8-mg) followed by 42 mg iv gtt in 90 min.Early routine catheterization after 3 hours but within 24 hours of the start of fibrinolytic therapy is performed, if required, PCI or, in case of insufficient ST resolution at 90 min,rescue PCI. The decision on rescue PCI will, however, be taken 90 min (or earlier if clinically indicated) after injection of alteplase according to the ST resolution (less than 50% reduction in ST-segment elevation).

Primary Outcome Measures

Name	Time	Method
Complete Epicardial and myocardial reperfusion;	Immediately after PCI	defined as TIMI Flow Grade 3 (TFG 3) for epicardial reperfusion and TIMI Myocardial Perfusion Grade 3 (TMPG 3) for myocardial reperfusionand resolution of the initial sum of ST-segment elevation ≥ 70% in 60 min post catheterisation

Secondary Outcome Measures

Name	Time	Method
TIMI Flow Grade (TFG)	Immediately after PCI	TIMI Flow Grade (TFG) assesses flow in the epicardial arteries.
TIMI Myocardial Perfusion Grade (TMPG)	Immediately after PCI	TMPG is an angiographic measure of myocardial perfusion.
ST-segment Resolution	Immediately after PCI	Resolution of the initial sum of ST-segment elevation ≥ 70%.
TIMI Frame Count (CTFC)	Immediately after PCI	CTFC is a continuous measurement assessing flow in the epicardial arteries.
TIMI Myocardial Perfusion Frame Count (TMPFC)	Immediately after PCI	TMPFC is a novel method to standardize and quantify myocardial perfusion by timing the filling and washout of contrast in the myocardium using cine-angiographic frame-counting. Briefly, the first frame of TMPFC was defined as the frame that clearly demonstrated the first appearance of myocardial blush beyond the IRA (F1). The last frame of TMPFC was then defined as the frame where contrast or myocardial blush disappeared (F2). TMPFC is F2-F1 frame counts at a filming rate of 15 frames/sec, or (F2-F1)×2 frame counts at the corrected filming rate of 30 frames/sec.
Wall motion score index (WMSI) by echocardiography	in-hospital and 30 day	The WMSI will be calculated as the sum of the scores in each segment divided by 16. Each segment will be given a score based on its systolic function (normal = 1, hypokinesis = 2, akinesis = 3).
Clinical Outcomes	30 days after randomization	All cause death, non-fatal reinfarction, heart failure, and stroke after randomization constitute the clinical endpoints.

Trial Locations

Locations (1)

RenJi Hospital; 🇨🇳 Shanghai, Shanghai, China