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

Acute ST-segment Elevation Myocardial Infarction Clinical Trial

— EARLY-MYO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01930682
• Other study ID #: BI135.326
• Secondary ID: 12410708300
• Status: Completed
• Phase: Phase 4
• First received: August 19, 2013
• Last updated: August 28, 2017
• Start date: January 13, 2014
• Est. completion date: September 12, 2016

Study information

• Verified date: August 2013
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: September 12, 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute ST-segment Elevation Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

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

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

Locations

Country	Name	City	State
China	RenJi Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Borgia F, Goodman SG, Halvorsen S, Cantor WJ, Piscione F, Le May MR, Fernández-Avilés F, Sánchez PL, Dimopoulos K, Scheller B, Armstrong PW, Di Mario C. Early routine percutaneous coronary intervention after fibrinolysis vs. standard therapy in ST-segment elevation myocardial infarction: a meta-analysis. Eur Heart J. 2010 Sep;31(17):2156-69. doi: 10.1093/eurheartj/ehq204. Epub 2010 Jul 2. Review. — View Citation

Canadian Cardiovascular Society; American Academy of Family Physicians; American College of Cardiology; American Heart Association, Antman EM, Hand M, Armstrong PW, Bates ER, Green LA, Halasyamani LK, Hochman JS, Krumholz HM, Lamas GA, Mullany CJ, Pearle DL, Sloan MA, Smith SC Jr, Anbe DT, Kushner FG, Ornato JP, Pearle DL, Sloan MA, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Halperin JL, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B, Tarkington LG, Yancy CW. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008 Jan 15;51(2):210-47. doi: 10.1016/j.jacc.2007.10.001. Review. Erratum in: J Am Coll Cardiol. 2008 Mar 4;51(9):977. — View Citation

Ding S, Pu J, Qiao ZQ, Shan P, Song W, Du Y, Shen JY, Jin SX, Sun Y, Shen L, Lim YL, He B. TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis. Catheter Cardiovasc Interv. 2010 Apr 1;75(5):722-32. doi: 10.1002/ccd.22298. — View Citation

Fernández-Avilés F, Alonso JJ, Peña G, Blanco J, Alonso-Briales J, López-Mesa J, Fernández-Vázquez F, Moreu J, Hernández RA, Castro-Beiras A, Gabriel R, Gibson CM, Sánchez PL; GRACIA-2 (Groupo de Análisis de Cardiopatía Isquémica Aguda) Investigators. Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA-2 non-inferiority, randomized, controlled trial. Eur Heart J. 2007 Apr;28(8):949-60. Epub 2007 Jan 23. — View Citation

Gibson CM. Primary angioplasty compared with thrombolysis: new issues in the era of glycoprotein IIb/IIIa inhibition and intracoronary stenting. Ann Intern Med. 1999 May 18;130(10):841-7. Review. — View Citation

Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008 Dec;29(23):2909-45. doi: 10.1093/eurheartj/ehn416. Epub 2008 Nov 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Main Safety Endpoints-Bleeding events	Incidence of bleeding events, classified by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) severity criteria	30 days after randomization
Other	Left Ventricular Function	Left ventricular function assessment by echocardiography and cardiac magnetic resonance	in-hospital and 30 day
Primary	Complete Epicardial and myocardial reperfusion;	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	Immediately after PCI
Secondary	TIMI Flow Grade (TFG)	TIMI Flow Grade (TFG) assesses flow in the epicardial arteries.	Immediately after PCI
Secondary	TIMI Myocardial Perfusion Grade (TMPG)	TMPG is an angiographic measure of myocardial perfusion.	Immediately after PCI
Secondary	ST-segment Resolution	Resolution of the initial sum of ST-segment elevation = 70%.	Immediately after PCI
Secondary	TIMI Frame Count (CTFC)	CTFC is a continuous measurement assessing flow in the epicardial arteries.	Immediately after PCI
Secondary	TIMI Myocardial Perfusion Frame Count (TMPFC)	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.	Immediately after PCI
Secondary	Wall motion score index (WMSI) by echocardiography	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).	in-hospital and 30 day
Secondary	Clinical Outcomes	All cause death, non-fatal reinfarction, heart failure, and stroke after randomization constitute the clinical endpoints.	30 days after randomization