Clinical trial NCT03252665: Efficacy of Intracoronary Infusion of Different Medicine in STEMI Patients Undergoing Primary PCI
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: ST Segment Elevation Myocardial Infarction
Keywords: STEMI
myocardial perfusion
TMPFC
Nicorandil
Alprostadil
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai 10th People's Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai 6th People's Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Ruijin Hospital
First posted: 2017-08-17
Enrollment: 600
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 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.

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.

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 ;
* Signed informed consent form prior to trial participation.

Exclusion Criteria:

1. Evidence of cardiac rupture;
2. ECG: new left bundle branch block;
3. Thrombolysis contradictions:
4. 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;
5. 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;
6. 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: TIMI Myocardial Perfusion Frame Count (TMPFC)
timeFrame: One mins after PCI
measure: TIMI Myocardial Perfusion Frame Count (TMPFC)
timeFrame: One mins after intracoronary medicine infusion post-PCI
measure: TIMI Myocardial Perfusion Grade (TMPG)
timeFrame: One mins after PCI
measure: TIMI Myocardial Perfusion Grade (TMPG)
timeFrame: One mins after intracoronary medicine infusion post-PCI
Secondary outcomes:
measure: ST-segment Resolution
timeFrame: 90 mins after PCI
measure: Myocardial-specific isoenzyme of creatine kinase (CK-MB) enzyme levels peri-PCI
timeFrame: Within 0 to 48 hours after enrollment
measure: TIMI Flow Grade (TFG)
timeFrame: One mins after PCI
measure: TIMI Flow Grade (TFG)
timeFrame: One mins after intracoronary medicine infusion post-PCI
measure: TIMI Frame Count (CTFC)
timeFrame: One mins after PCI
measure: TIMI Frame Count (CTFC)
timeFrame: One mins after intracoronary medicine infusion post-PCI
measure: Wall motion score index (WMSI) and LVEF by echocardiography
timeFrame: Echocardiography was performed 3-5 days after PCI
measure: CMR defined MVO
timeFrame: 3-5 days post-infarct
measure: Infarct Size by Cardiac Magnetic Resonance Imaging (CMR)
timeFrame: 3-5 days post-infarct
Other outcomes:
measure: MACE
timeFrame: in-hospital (within 14 days)
measure: MACE
timeFrame: 30 days after randomization
Locations:
city: ShangHai
country: China
facility: Ren Ji Hospital Afflited to School of Medicine, Shanghai Jiao Tong University
Study officials:
affiliation: Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
name: Ben He, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
citation: Gibson CM, Cannon CP, Murphy SA, Ryan KA, Mesley R, Marble SJ, McCabe CH, Van De Werf F, Braunwald E. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000 Jan 18;101(2):125-30. doi: 10.1161/01.cir.101.2.125.
citation: van 't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation. 1998 Jun 16;97(23):2302-6. doi: 10.1161/01.cir.97.23.2302.
citation: Chinese Society of Cardiology of Chinese Medical Association; Editorial Board of Chinese Journal of Cardiology. [Guideline of non-ST segment elevation acute coronary syndrome]. Zhonghua Xin Xue Guan Bing Za Zhi. 2012 May;40(5):353-67. No abstract available. Chinese.
citation: Kidambi A, Mather AN, Motwani M, Swoboda P, Uddin A, Greenwood JP, Plein S. The effect of microvascular obstruction and intramyocardial hemorrhage on contractile recovery in reperfused myocardial infarction: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2013 Jun 27;15(1):58. doi: 10.1186/1532-429X-15-58.
citation: Roe MT, Ohman EM, Maas AC, Christenson RH, Mahaffey KW, Granger CB, Harrington RA, Califf RM, Krucoff MW. Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion. J Am Coll Cardiol. 2001 Jan;37(1):9-18. doi: 10.1016/s0735-1097(00)01101-3.
citation: Pu J, Shan P, Ding S, Qiao Z, Jiang L, Song W, Du Y, Shen J, Shen L, Jin S, He B. Gender differences in epicardial and tissue-level reperfusion in patients undergoing primary angioplasty for acute myocardial infarction. Atherosclerosis. 2011 Mar;215(1):203-8. doi: 10.1016/j.atherosclerosis.2010.11.019. Epub 2010 Nov 26.
citation: Pu J, Ding S, Shan P, Qiao Z, Song W, Du Y, Shen J, Jin S, He B. Comparison of epicardial and myocardial perfusions after primary coronary angioplasty for ST-elevation myocardial infarction in patients under and over 75 years of age. Aging Clin Exp Res. 2010 Aug;22(4):295-302. doi: 10.1007/BF03337726. Epub 2009 Dec 1.
citation: Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
citation: Shen LH, Wan F, Shen L, Ding S, Gong XR, Qiao ZQ, Du YP, Song W, Shen JY, Jin SX, Pu J, Yao TB, Jiang LS, Li WZ, Zhou GW, Liu SW, Han YL, He B. Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study. J Thromb Thrombolysis. 2012 Jan;33(1):101-8. doi: 10.1007/s11239-011-0657-7.
citation: Zhang W, Dai J, Zheng X, Xu K, Yang X, Shen L, Wang X, Hao Z, Qiu X, Jiang L, Shi H, Shen L, He B. Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial. Medicine (Baltimore). 2021 Apr 16;100(15):e25551. doi: 10.1097/MD.0000000000025551.