Clinical trial NCT03074214: Prognostic Value of Copeptin for Infarct Size and Prognosis in Patients With ST-elevation Myocardial Infarction
Official title: Study of Prognostic Value of Copeptin for Myocardial Infarct Size and 6-month Prognosis in Patients With ST-elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: GOOD I Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: ST-elevation Myocardial Infarction
Keywords: copeptin
myocardial infarct size
prognosis
ST-elevation myocardial infarction
percutaneous coronary intervention
Lead sponsor: Shengjing Hospital
Sponsor class: OTHER
First posted: 2017-03-08
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 275 patients with STEMI receiving PPCI in department of Cardiology, Shengjing Hospital of China Medical University from March 1, 2017 to February 28, 2019

Brief summary: ST-elevation myocardial infarction (STEMI) has a serious health threaten to population. PCI, which can timely restore the blood flow to the ischemic myocardium, is a well-proved measure in STEMI management. However, the process of the restoration can induce injury. The phenomenon is defined as ischemia/reperfusion (I/R) injury. The studies indicate that I/R injury accounts for up to 50% of the final myocardial infarct size. However, previous attempts to target known mediators of myocardial I/R injury in patients have been disappointing, leading to calls for a reevaluation of factors affecting myocardial I/R injury \[1\]. Arginine vasopressin (AVP), that response to acute illness, is unstable and cleared rapidly from the circulation. However, copeptin, the C-terminal portion of provasopressin, is released in equimolar amounts to AVP and is easy to determine. So, copeptin can be a surrogate marker for AVP secretion. Recently, copeptin was found to serve as a potential prognostic biomarker in heart failure and acute myocardial infarction (AMI). AMI can activate the AVP axis, which have a causative role in the evolution of heart failure. Increasing copeptin was shown to correlate with myocardial remodeling, mortality and morbidity. In patients with STEMI, myocardial infarct size is a stronger outcome predictor than LV function, and is related to LV remodeling, which often indicates a significant worse prognosis after AMI. As the gold standard for characterisation of cardiac structure and function, cardiac magnetic resonance (CMR) parameters can serve as surrogate end points in clinical trials of STEMI. We hypothesised that plasma copeptin values, tested before and after PCI, are related to myocardial infarct size, myocardial function both and outcomes at baseline and 6 months follow-up as assessed by CMR in patients with STEMI.

Detailed description: Acute myocardial infarction (AMI) is a major concern in public health in China. Ischemia/reperfusion injury cripples the treatment effect of reperfusion management, and increases the final myocardial infarct size. Copeptin is related to the prognosis of heart failure and AMI, and may be a potential prognostic biomarker for myocardial infarct size, myocardial function and outcomes in patients with STEMI undergoing PCI.This study will enroll consecutive STEMI patients undergoing PCI, who meet the inclusion and exclusion criteria, in a large-scale hospital in Northeast China. After obtaining an informed consent, blood samples will be drawn at the time of before, immediately after, and 3 days after PPCI. They will be collected in EDTA tubes and centrifuged for 10 min at 2000 g within 0.5 h. Plasma will be stored at -80°C until analysis. Plasma copeptin concentrations will be determined by a commercially available automated immunofluorescent assay (R\&D Systems Inc. Minneapolis, USA). And other information about symptoms, functioning, quality of life, medical care, demographic characteristics, medical history, clinical features, diagnostic tests, medications and procedural data will be also collected. Baseline CMR will be performed 3-5 days after PPCI. All scans were performed on a 3.0 Tesla scanner. At 1 month, 3 month, and 12 month after discharge, participants will receive a follow-up by phone. At 6 month after discharge, participants will return to the clinic for follow up visits, and a face-to-face interview will be conducted to get information about clinical events, symptoms, functioning, quality of life, and medical care during the recovery period. Follow-up CMR scan will be conducted. Follow-up blood samples will be drawn for testing copeptin.

Sample Size Calculation A study size analysis was performed using PASS (version 11.0.4, 2011, NCSS, LLC, USA). In a previous study, the 90-day primary composite end point of all-causes death, ventricular fibrillation, cardiogenic shock, and congestive heart failure requiring rehospitalization or an emergency room visit through 90 days was 10.3% in STEMI patients undergoing PCI. \[1\] Although available data for detecting clinically relevance between copeptin and prognosis in STEMI patients undergoing PCI was limited, a previous study demonstrated that a high concentration (quartile 4 vs. quartiles 1 to 3) of copeptin identified an increased risk of CV death or HF (HR:2.80,95%CI:2.24-3.51,P\<0.001). \[2\] When the ratio between groups1 and 2 is 3:1, an overall sample size of 275 subjects, of which 207 are in group 1 and 68 are in group 2, achieves 90% power at a 0.0500 significance level to detect a difference of 0.1280 between 0.9290 and 0.8010--the proportions surviving in groups 1 and 2, respectively. The proportion of patients lost during follow up was 0.1000.

Eligibility criteria: Inclusion Criteria:

1. chest pain present less than 12 hours from onset of pain to time of catheterization;
2. significant ST-segment elevation (at least 0.1 mV in two or more standard leads or at least 0.2 mV in two or more contiguous precordial leads) or a new left bundle branch block;
3. receiving primary PCI.

Exclusion Criteria:

1. Patients with conditions other than STEMI that could cause increased copeptin levels, such as renal dysfunction (eGFR\<30 ml/min), liver failure, respiratory tract infection, stroke, sepsis, hyponatremia (Serum sodium concentration\<135mmol/L), central diabetes insipidus or malignancy;
2. Patients with contraindications to perform cardiac magnetic resonance;
3. Patients with cardiogenic shock (Killip class IV);
4. Patients in whom reperfusion therapy failed;
5. Patients who were referred for emergency coronary artery bypass grafting (CABG) in view of unfavourable coronary anatomy.

Primary outcomes:
measure: Major adverse cardiovascular events (MACE)
timeFrame: 6 months
Secondary outcomes:
measure: All-cause death
timeFrame: 6 months
measure: Cardiac death
timeFrame: 6 months
measure: unplanned repeat revascularization
timeFrame: 6 months
measure: congestive heart failure requiring rehospitalization or an emergency room visit
timeFrame: 6 months
measure: angina requiring rehospitalization or an emergency room visit
timeFrame: 6 months
measure: ventricular fibrillation or severe ventricular tachycardia
timeFrame: 6 months
measure: acute heart failure during the index hospitalization
timeFrame: 6 months
measure: in-stent stent thrombosis
timeFrame: 6 months
measure: contrast-induced nephropathy
timeFrame: 6 months
measure: ischemia stroke
timeFrame: 6 months
measure: Bleeding Academic Research Consortium Definition for Bleeding: type 3 or 5
timeFrame: 6 months
measure: Seattle angina questionnaire (SAQ)
timeFrame: 6 months
measure: Quality of life (EQ-5D)
timeFrame: 6 months
measure: Depression (PHQ-8)
timeFrame: 6 months
measure: Stress (Chinese 14-item PSS)
timeFrame: 6 months
measure: Cognitive function (MMSE)
timeFrame: 6 months
measure: myocardial infarct size
timeFrame: 6 months
Other outcomes:
Locations:
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
Study officials:
affiliation: Shengjing Hospital
name: Zhaoqing Su, Doctor
role: STUDY_CHAIR
References:
citation: Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, Andersen HR, Betriu A, Savonitto S, Adamus J, Peruga JZ, Kosmider M, Katz O, Neunteufl T, Jorgova J, Dorobantu M, Grinfeld L, Armstrong P, Brodie BR, Herrmann HC, Montalescot G, Neumann FJ, Effron MB, Barnathan ES, Topol EJ; FINESSE Investigators. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008 May 22;358(21):2205-17. doi: 10.1056/NEJMoa0706816.
citation: O'Malley RG, Bonaca MP, Scirica BM, Murphy SA, Jarolim P, Sabatine MS, Braunwald E, Morrow DA. Prognostic performance of multiple biomarkers in patients with non-ST-segment elevation acute coronary syndrome: analysis from the MERLIN-TIMI 36 trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36). J Am Coll Cardiol. 2014 Apr 29;63(16):1644-53. doi: 10.1016/j.jacc.2013.12.034. Epub 2014 Feb 13.