Accelerated Rule-Out of Acute Myocardial Infarction, Using Copeptin and High Sensitive Troponin T - the AROMI Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 4,516
- 试验地点
- 6
- 主要终点
- Duration of hospital stay
研究概览
简要总结
Every year > 50.000 people in Denmark are hospitalized with a suspected acute myocardial infarction (AMI). The majority has other explanations of their chest discomfort and most are discharged again without any initiation of treatment. Still, the suspicion dictates acute ambulance deployment, hospital admission to a highly specialized cardiac unit, cardiac surveillance and cardiac troponin blood sampling. The novel biomarker copeptin, a byproduct of vasopressin production, is released immediately from the pituitary gland as part of the hormonal response to AMI. Peak concentrations are reached within the first hour. Previous studies have suggested the combination of copeptin and cardiac troponin for fast and reliable rule out of AMI. However, the blood sampling should be performed as soon as possible after symptom onset, preferably already during the prehospital phase.
We aim, in an open randomized setting, to investigate the combined measurement of prehospital copeptin and in-hospital high sensitive cardiac Troponin T compared to the standard rule-out procedure of suspected myocardial infarction. We hypothesize that the combined measurement of prehospital copeptin and in-hospital high sensitive troponin T:
- Reduces admission time by 1.5 hours in patients where AMI is ruled out
- Reduces the time to disposition
- Is non-inferior compared to the standard rule-out procedure in relation to major adverse cardiovascular events.
- Is more cost efficient compared to standard diagnostic strategy
详细描述
Patients with suspected Acute Myocardial Infarction (AMI) constitute one of the largest patient groups in emergency medicine. The majority of these patients, however, have other causes than AMI, for their chest discomfort and many are discharged again without any initiation of treatment.(1) At present, cardiac troponin is gold standard in diagnosing AMI. Diagnostic levels of troponin are not reached until hours after onset of symptoms and serial sampling is recommended at intervals of 3-6 hours to confirm or rule-out AMI. The novel biomarker copeptin, a by-product of vasopressin production, is released immediately from the pituitary gland as part of the hormonal response to AMI. However, copeptin elevation, is not specific of AMI. Peak concentrations of copeptin are reached within the first hour and the values normalizes within 4-10 hours.(3) Previous studies have suggested the combination of copeptin and high-sensitive cardiac troponin T (hs-cTnT) for early and reliable rule-out of AMI.(2,3,6) These studies are based on copeptin measurement in blood sample acquired at hospital admission. However, because of the rapid release of copeptin, the blood sampling should be performed as early as possible after symptom onset, preferably already in the ambulance, whereas the analysis can be performed after arrival at the hospital because copeptin is stable. The PREHAB trial conducted in the Central Denmark Region, documented that prehospital blood sampling is performed 70 minutes earlier than first in-hospital sample.(5) Post-trial analysis of blood samples from the PREHAP trial has demonstrated the potential for early and safe rule-out of AMI using the combination of prehospital copeptin and in-hospital troponin analysis. AMI could potentially be safely, ruled out in approximately 40-50% of patients, in whom the AMI diagnosis eventually was dismissed.
During the last 7 years, studies have evaluated the effect and validity of prehospital blood sample analysis. This is now standard procedure in The Central Denmark Region, Denmark.(5) Currently, prehospital blood sampling is carried out in two major randomized studies, aiming at identifying patients with myocardial infarction and heart failure (NCT01638806 and NCT02050282).
Unfortunately, there is at present no point-of-care analysis equipment for copeptin available. Manufacturer of copeptin analysis equipment, Thermo Fischer, has informed that the development of point-care-care equipment is in process, but will not be available in near future. Therefore, we will perform in-hospital analysis of the prehospital blood samples.
Overall aim of this protocol is to demonstrate the combination of troponin T and copeptin as a safe and effective biomarker for rule-out of AMI. In a randomized setting, we will compare the combination of prehospital copeptin and in hospital hs-cTnT, to the standard diagnostic procedure in patients with suspected AMI, evaluating rule-out potential and potential for reduction of the length of stay at the hospital. The diagnostic effects of measuring copeptin/ hs-cTnT in prehospital vs in-hospital blood samples will be evaluated. Moreover an other diagnostic rule-out strategy, using hs-cTNT at admission and 1 hour after admission, will be evaluated in retrospective analysis of blood samples acquired from patients in the conventional diagnostics arm of the study.
Primary purposes of the AROMI trial:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients which, after telemedical triage, are admitted to a cardiac department in suspicions of myocardial infarction
- •A peripheral venous catheter has been inserted prehospitally and blood has drawn from it, before flushing it.
排除标准
- •Age below 18 years
- •Patients in which an informed concent can not be obtained (psychiatric disease, dementia, under influence of drugs etc.),
- •Suspected STEMI and referral to Primary percutaneous coronary intervention (PPCI), referral to a highly specialized cardiac department for another cardiac reason (e.g ventricular tachycardia, ventricular fibrillation, 3° Atrio-ventricular block.)
- •Known central Diabetes insipidus
- •Other diagnosis as obvious reason for symptoms at time of admittance (e.g. a new diagnosis of supraventricular tachycardia, pulmonary embolism, aortic dissection) AND no suspicions of ACS
结局指标
主要结局
Duration of hospital stay
时间窗: Up to three months from randomization
Time (hours and minutes) from admission to discharge from cardiac department. Reported by clinical personnel in registration form and supplemented by data from the national health registry. Will be evaluated in interim analysis after inclusion of 300 patients in each site.
Combined MACE
时间窗: Within time from randomization to 30 days after randomization
Combined endpoint of major adverse cardiac events, consisting of: "All-cause mortality", "survived cardiac arrest", "Confirmed or Readmission with Acute Coronary Syndrome(ACS)", "Non-scheduled coronary intervention", and "Life-threatening arrhythmias" (see below for description) occuring within time from randomization to 30 days after randomization
次要结局
- Time to disposition(Within 24 h of randomization)
- All-cause mortality(Within index admission and within 30, 90 and 365 days of randomization)
- Non-scheduled coronary intervention(Within index admission and within 30, 90 and 365 days of randomization)
- Life-threatening arrhythmias(Within index admission and within 30, 90 and 365 days of randomization)
- Combined MACE(Within index admission, within time from discharge to 30, 90, and 365 days after randomization, and within time from randomization to 90 and 365 days after randomization)
- Confirmed diagnosis of ACS or readmission with ACS(Within index admission and within 30, 90 and 365 days of randomization)
- Survived, cardiac arrest(Within index admission and within 30, 90 and 365 days of randomization)
研究者
Christian Juhl Terkelsen
Associate professor, MD, DmSc, PhD
Aarhus University Hospital Skejby