Clinical trial NCT01930682: EARLY Routine Catheterization After Alteplase Fibrinolysis vs. PPCI in ST-Segment-Elevation MYOcardial Infarction
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute ST-segment Elevation Myocardial Infarction
Keywords: Myocardial Infarction
Catheterization
Fibrinolysis
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2013-08-29
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Epicardial and myocardial reperfusion;
timeFrame: Immediately after PCI
Secondary outcomes:
measure: TIMI Flow Grade (TFG)
timeFrame: Immediately after PCI
measure: TIMI Myocardial Perfusion Grade (TMPG)
timeFrame: Immediately after PCI
measure: ST-segment Resolution
timeFrame: Immediately after PCI
measure: TIMI Frame Count (CTFC)
timeFrame: Immediately after PCI
measure: TIMI Myocardial Perfusion Frame Count (TMPFC)
timeFrame: Immediately after PCI
measure: Wall motion score index (WMSI) by echocardiography
timeFrame: in-hospital and 30 day
measure: Clinical Outcomes
timeFrame: 30 days after randomization
Other outcomes:
measure: Main Safety Endpoints-Bleeding events
timeFrame: 30 days after randomization
measure: Left Ventricular Function
timeFrame: in-hospital and 30 day
Locations:
city: Shanghai
country: China
facility: RenJi Hospital
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Ben He, MD
role: STUDY_DIRECTOR
References:
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. No abstract available.
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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.
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citation: Pu J, Ding S, Ge H, Han Y, Guo J, Lin R, Su X, Zhang H, Chen L, He B; EARLY-MYO Investigators. Efficacy and Safety of a Pharmaco-Invasive Strategy With Half-Dose Alteplase Versus Primary Angioplasty in ST-Segment-Elevation Myocardial Infarction: EARLY-MYO Trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment-Elevation Myocardial Infarction). Circulation. 2017 Oct 17;136(16):1462-1473. doi: 10.1161/CIRCULATIONAHA.117.030582. Epub 2017 Aug 27.