Early rhBNP on Myocardial Remodeling and Reperfusion in Patients With STEMI

Prospective Observational Clinical Study：The Impact of Early rhBNP on Myocardial Remodeling and Reperfusion in Patients With ST-segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention

The study intends to evaluate the efficacy of early rhBNP on myocardial remodeling and reperfusion in patients with ST-segment elevation myocardial infarction after percutaneous coronary intervention

Study Overview

• Status: Recruiting
• Conditions: ST Segment Elevated Myocardial Infarction
• Intervention / Treatment: Drug: rhBNP; Drug: Control

Detailed Description

As prospectively observational study，it brings anterior acute myocardial infarct patients from 2018 JAN. to 2019 JAN, whose predefined time between symptom onset and percutaneous is not more than 12 hours. The door-to-balloon time, present to balloon time and first medical contact-to-balloon time will be documented. ECG in FMC and 90min after PCI also will be record. Patients assigned to the rhBNP group will receive intravenous rhBNP before PCI，and the variety of heart rate and blood pressure will be record. Routinely evaluation of corrected TIMI frame counting（CTFC）, TIMI myocardial perfusion frame counting and TIMI myocardial perfusion grade(TMPG).Blood tests including BNP, CK-MB and CRP are measured at admission and6, 12, 24, 48 hours after PCI. Both Cardiovascular magnetic imaging and echocardiography will be applied in Day 30 and 12 months. The composite endpoint is incidence of all-cause mortality, reinfarct, stroke and target vessel revascularization at hospitalization and follow-up. Principally patients are prevented from any drug affecting microcirculation (GPIIb/IIa receptor agonist, vascular dilation drug, etc.), otherwise it is necessary, which should be documented.

• Study Type: Interventional
• Enrollment (Estimated): 352
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jun Pu, MD,PhD; Phone Number: 86-21-68383477; Email: pujun310@hotmail.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Ren Ji Hospital Afflited to School of Medicine, Shanghai Jiao Tong University
    • Contact: Jun Pu, MD,PhD; Phone Number: 86-21-68383477; Email: pujun310@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patients are eligible for enrollment if they are suspected as anterior myocardial infarct (anterior myocardial infarct is defined as persistent chest pain for 30 mins at least, with ST-segment elevation of at least 0.2 mV in two or more contiguous precordial leads) within 12 hours after onsets of symptom, and no contraindication for rhBNP. The coronary angiography (CAG) proves left anterior descending (LAD) as culprit vessel, which was totally or nearly occlusion with TIMI 0-1 grade and resulted in TIMI 3 grade after PCI.

Exclusive criteria:

1. Killips grade III-IV.
2. unstable hemodynamic; with A-V block or atrial fibrillation;
3. Contraindication of magnetic resonance, such as history of metal, ICD or paceman implant;
4. history of myocardial infarct;
5. pregnancy or breeding;
6. combined with other serious diseases: severe renal dysfunction (creatinine clearance<30ml/min;), liver failure, neutropenia, thrombocytopenia, acute pancreatitis；
7. life expectancy≤12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhBNP; rhBNP intra-coronary injection 1.5 ug/kg loading dose, with intravenous injection 0.0075-0.01 ug/kg/min persistent for 72 hour.	Drug: rhBNP; rhBNP intra-coronary injection 1.5 ug/kg loading dose, with intravenous injection 0.0075-0.01 ug/kg/min persistent for 72 hour.
Placebo Comparator: Control; saline intra-coronary injection 0.15ml/kg loading dose, with same intravenous injection speed for 72 hour after randomization.	Drug: Control; saline intra-coronary injection 0.15ml/kg loading dose, with same intravenous injection speed for 72 hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compound endpoints of epicardium and endocardium perfusion	Both the TIMI and TMPG score reach 3 immediately after PCI, besides ST resolution≥70% at 90min after PCI.	90min after infarct related artery revascularization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIMI Flow Grade (TFG)	TIMI Flow Grade (TFG)assesses flow in the epicardial arteries	One mins after PCI
TIMI Frame Count (CTFC)	CTFC is a continuous measurement assessing flow in the epicardial arteries.	One mins after PCI
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	One mins after PCI
TIMI Myocardial Perfusion Grade (TMPG)	TMPG is an angiographic measure of myocardial perfusion	One mins after PCI
ST-segment Resolution	Resolution of the initial sum of ST-segment elevation ≥ 70%	90 mins after PCI
Wall motion score index (WMSI) and LVEF by echocardiography	Echocardiographic index includes WMSI and LVEF	Day 1, 3, 7, 30 and 12 month after PCI
CMR imaging	CMR imaging will be collected using a 3.0-Tesla-scanner (Achieva, Philips Healthcare, The Netherlands) under electrocardiogram-triggered gating in School Shanghai Jiaotong University school of medicine RenJi hospital.	Day 1, 3, 7, 30 and 12 month after PCI

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemodynamic adverse related to rhBNP	low perfusion sign, and Noninvasive systolic blood pressure is below 90mmHg with or without diastolic blood pressure below 60mmHg, Excluding other reason.	72 hour since rhBNP administration

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University; Shanghai 6th People's Hospital; Shanghai Minhang Central Hospital; Suqian First People's Hospital in Jiangsu Province
• Investigators: Principal Investigator: Jun Pu, MD,PhD, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong Univers

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Actual): August 1, 2020
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: cardiac magnetic resonance; Microvascular disease; rhBNP; ventricular remodeling; ST Segment Elevated Myocardial Infarction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: rhBNP-myocardium

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No