Efficacy of Intracoronary Infusion of Different Medicine in STEMI Patients Undergoing Primary PCI

Sponsor

RenJi Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03252665

Collaborator

Shanghai 10th People's Hospital (Other), Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Other), Shanghai 6th People's Hospital (Other), Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other), Ruijin Hospital (Other)

600

Enrollment

Location

Arms

21.9

Anticipated Duration (Months)

27.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study intends to evaluate the efficacy of different medicine delivering by targed perfusion catheter incoronary administration on epicardial, myocardial perfusion and clinical outcomes in STEMI patients undergoing primary PCI.

Condition or Disease	Intervention/Treatment	Phase
ST Segment Elevation Myocardial Infarction	Drug: Alprostadil Drug: Nicorandil Drug: Nitroglycerin	Phase 4

Detailed Description

The goal of STEMI therapy is to successfully restore both epicardial blood flow and myocardial perfusion. PCI has been documented as being the most effective method for restoration of epicardial blood flow. However, epicardial blood flow does not necessarily equate to myocardial perfusion; not every patient with TIMI 3 flow after successful PCI achieves effective myocardial tissue-level perfusion. Although epicardial TIMI 3 flow could be restored in >90% of STEMI patients undergoing PCI, normalization of myocardial perfusion was achieved less frequently, with detrimental impacts on survival。 Currently, there are two main methods of angiographic assessment of myocardial perfusion: TIMI myocardial perfusion grading (TMPG), described by Gibson et al. and myocardial blush grading (MBG), described by Van't Hof et al. These established myocardial perfusion parameters, TMPG and MBG, have been widely used in various important trials and are reported to be highly useful in predicting clinical outcomes. However, visual assessment of these methods is categorical, subjective, and operator dependent. TIMI Myocardial Perfusion Frame Count (TMPFC), a novel and objective method that measures the filling and clearance of contrast in the myocardium using cine-angiographic frame-counting, was developed by our center to quantify myocardial tissue- level perfusion and was proved to be a predictive value on clinical prognosis.

Currently, there are two main types of interventions to improve myocardial perfusion . One kind is the mechanical method, which included thrombus aspiration catheter and the distal protective devices. It has been confirmed that the mechanical method can effectively improve epicardial and myocardial perfusion in patient with part of large vessels and high burden thrombus. But for patients with small vessels and no obvious visual thrombus, the efficacy is not significant.

The other kind intervention is medicine which included GP IIb/IIIa receptor antagonist , adenosine , sodium nitroprusside, verapamil etc. Part of the drugs have some effect but the overall clinical efficacy is still not satisfied.

The study intends to use targeted perfusion catheter to deliver drug to the distal targeted blood vessels. TMPFC and TMPG are applied to evaluate the efficacy of treatment with Nicorandil versus Alprostadil on myocardial tissue-level perfusion in STEMI patients undergoing primary PCI.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy of Intracoronary Infusion of Different Medicine With Targeted Perfusion Catheter on Myocardial Perfusion in Patients With STEMI Undergoing Primary PCI:an Open,Prospective,Randomized,Multicenter Trial.

Anticipated Study Start Date :

Sep 1, 2017

Anticipated Primary Completion Date :

Jun 30, 2019

Anticipated Study Completion Date :

Jun 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: alprostadil alprostadil,2ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients	Drug: Alprostadil alprostadil,2ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients
Experimental: nicorandil nicorandil,2mg, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients	Drug: Nicorandil Nicorandil,2mg, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients
Placebo Comparator: nitroglycerin nitroglycerin,200ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients	Drug: Nitroglycerin Nitroglycerin,200ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Arm

Intervention/Treatment

Experimental: alprostadil

alprostadil,2ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Drug: Alprostadil

alprostadil,2ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Experimental: nicorandil

nicorandil,2mg, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Drug: Nicorandil

Nicorandil,2mg, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Placebo Comparator: nitroglycerin

nitroglycerin,200ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Drug: Nitroglycerin

Nitroglycerin,200ug, dilivered by targeted perfusion catheter in the culprit vessel after PCI in STEMI patients

Outcome Measures

Primary Outcome Measures

TIMI Myocardial Perfusion Frame Count (TMPFC) [One mins 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
TIMI Myocardial Perfusion Frame Count (TMPFC) [One mins after intracoronary medicine infusion post-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
TIMI Myocardial Perfusion Grade (TMPG) [One mins after PCI]
TMPG is an angiographic measure of myocardial perfusion
TIMI Myocardial Perfusion Grade (TMPG) [One mins after intracoronary medicine infusion post-PCI]
TMPG is an angiographic measure of myocardial perfusion

Secondary Outcome Measures

ST-segment Resolution [90 mins after PCI]
Resolution of the initial sum of ST-segment elevation ≥ 70%
Myocardial-specific isoenzyme of creatine kinase (CK-MB) enzyme levels peri-PCI [Within 0 to 48 hours after enrollment]
Infarct size is measured by the myocardial-specific isoenzyme of creatine kinase (CK-MB) area under the curve, calculated by the linear-trapezoidal method. If the baseline or last value is missing, the corresponding value will be set to zero. For missing values of intermediate time points, linear interpolation is used.
TIMI Flow Grade (TFG) [One mins after PCI]
TIMI Flow Grade (TFG)assesses flow in the epicardial arteries
TIMI Flow Grade (TFG) [One mins after intracoronary medicine infusion post-PCI]
TIMI Flow Grade (TFG)assesses flow in the epicardial arteries
TIMI Frame Count (CTFC) [One mins after PCI]
CTFC is a continuous measurement assessing flow in the epicardial arteries.
TIMI Frame Count (CTFC) [One mins after intracoronary medicine infusion post-PCI]
CTFC is a continuous measurement assessing flow in the epicardial arteries.
Wall motion score index (WMSI) and LVEF by echocardiography [Echocardiography was performed 3-5 days after PCI]
Echocardiographic index includes WMSI and LVEF
CMR defined MVO [3-5 days post-infarct]
MVO was defined as hypoenhanced area within infracted zone measured by CMR
Infarct Size by Cardiac Magnetic Resonance Imaging (CMR) [3-5 days post-infarct]
Infarct size (expressed as a percentage of LV myocardial mass) between two groups 3-5 days post-infarct assessed by the extent of late gadolinium enhancement on CMR

Other Outcome Measures

MACE [in-hospital (within 14 days)]
MACE includes all cause death, reinfarction, target vessel revascularization, and stroke
MACE [30 days after randomization]
MACE includes all cause death, reinfarction, target vessel revascularization, and stroke

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 ;
Signed informed consent form prior to trial participation.

Exclusion Criteria:

Evidence of cardiac rupture;
ECG: new left bundle branch block;
Thrombolysis contradictions:
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.