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

Sponsor

RenJi Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01930682

Collaborator

(none)

344

Enrollment

Location

Arms

Actual Duration (Months)

10.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute ST-segment Elevation Myocardial Infarction	Drug: Alteplase Procedure: Early post-fibrinolytic catheterisation Procedure: Primary PCI	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

344 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

EARLY Routine Catheterization or Rescue Angioplasty After Alteplase Fibrinolysis vs. Primary Angioplasty in Acute ST-elevation MYOcardial Infarction: An Open, Prospective, Randomized, Multicentre Trial

Actual Study Start Date :

Jan 13, 2014

Actual Primary Completion Date :

Sep 1, 2016

Actual Study Completion Date :

Sep 12, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: Alteplase Alteplase is given as a intravenous bolus (8-mg) followed by 42 mg iv gtt in 90 min. Other Names: rt-PA Procedure: Early post-fibrinolytic catheterisation Early post-fibrinolytic catheterisation 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).
Other: Primary PCI For STEMI Patients,primary PCI is performed without fibrinolytic therapy.	Procedure: Primary PCI For STEMI Patients,primary PCI is performed within 12 hours after the onset.

Arm

Intervention/Treatment

Experimental: 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).

Drug: Alteplase

Alteplase is given as a intravenous bolus (8-mg) followed by 42 mg iv gtt in 90 min.

Other Names:

rt-PA

Procedure: Early post-fibrinolytic catheterisation

Early post-fibrinolytic catheterisation 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).

Other: Primary PCI

For STEMI Patients,primary PCI is performed without fibrinolytic therapy.

Procedure: Primary PCI

For STEMI Patients,primary PCI is performed within 12 hours after the onset.

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

Main Safety Endpoints-Bleeding events [30 days after randomization]
Incidence of bleeding events, classified by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) severity criteria
Left Ventricular Function [in-hospital and 30 day]
Left ventricular function assessment by echocardiography and cardiac magnetic resonance

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Evidence of cardiac rupture;
ECG: new left bundle branch block;
"Diagnosis to balloon inflation" time over 3 hours;
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;

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;

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;

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.