Effect of the Biomarker Copeptin in Managing Patients With Suspected Acute Coronary Syndrome (ACS) (BiC-8)

• Rate of major adverse cardiac events (MACE) within 30 days Copeptin vs. Control arm. [ Time Frame: 30 days after discharge ] [ Designated as safety issue: Yes ]
  Rate of MACE (all- cause death or survived sudden cardiac arrest, myocardial infarction, re-hospitalisation for acute coronary syndrome, acute unplanned PCI, coronary artery bypass grafting (CABG) and documented life-threatening arrhythmias (VF, VT, AV-block III)) within 30 days Copeptin vs. Control arm (non-inferiority).
  
  

• Proportion of patients in whom coronary angiography (CA) is performed Copeptin vs. Control arm. [ Time Frame: within 30 days after discharge ] [ Designated as safety issue: No ]

  Efficacy endpoint

  • Rate of Patients in whom CA is performed
  • Rate of Patients with PCI after Index CA
  • Rate of Patients with CABG after Index CA
  
  
• Rate of ALL major adverse cardiac events (MACE) [ Time Frame: 90 days after discharge ] [ Designated as safety issue: Yes ]

  Rate of ALL MACE at 90 days

  • all- cause death or survived sudden cardiac arrest
  • myocardial infarction
  • re-hospitalisation for acute coronary syndrome
  • acute unplanned PCI
  • coronary artery bypass grafting (CABG)
  • documented life-threatening arrhythmias (VF, VT, AV-block III)
  
  
• Patient satisfaction regarding management within the ED/CPU [ Time Frame: no specific time frame, before discharge ] [ Designated as safety issue: No ]
  Patient satisfaction regarding management before discharge from ED/CPU
  
  
• Length of hospital stay [ Time Frame: within 30 days after discharge ] [ Designated as safety issue: No ]

  Duration of hospital stay

  • Length of stay at the Emergency Room
  • Length of hospital stay in the CPU
  • Length of stay in an intensive care unit (ICU)
  • Total length of hospital stay in hours including time as an inpatient on other wards
  
  

The management of patients with suspected Non-ST elevation acute coronary syndrome (NSTEACS) can be time-consuming and expensive. Often patients need to be hospitalized for precautionary medical treatment and serial Troponin testing until further decisions can be made.

Copeptin, a 39 amino acid glycopeptide, is the C-terminal portion of Pro-Vasopressin. It is co-secreted from the posterior pituitary gland together with Vasopressin and mirrors the amount of Vasopressin in the circulation. Vasopressin is primarily known as Anti-Diuretic Hormone (ADH), which acts in the kidney to regulate the body's retention of water and in high concentration causes arterial vasoconstriction.

Vasopressin is, as a central hormone, also a crucial part of the hypothalamo-pituitary-adrenal axis, which responds to severe, life-threatening "stress inputs"; its levels reflect the body's individual stress level.Vasopressin itself has a half-life of 5-10 minutes and is therefore difficult to measure in-vivo. Copeptin is secreted stoichiometrically with Vasopressin, it remains stable for days after blood withdrawal and can therefore easily be measured. Copeptin has been studied as a diagnostic and prognostic marker since 2006. In acute myocardial infarction Copeptin levels have been shown to increase early after the onset of symptoms (0-4 hours) and start decreasing after 4-5 hours.

In acute myocardial infarction (AMI) Copeptin levels increase early after the onset of symptoms. In patients with suspected ACS Copeptin levels were significantly higher in patients with AMI than in patients with other diagnoses. Copeptin in conjunction with Troponin T was particularly useful as a rule-out marker of AMI.

This is a randomized controlled diagnostic trial to quantify the benefit of integrating Copeptin into the management process of patients with NSTEACS and a negative baseline Troponin I test result in the Chest Pain Unit (CPU). Patient management will depend on Copeptin rather than serial Troponin results. Patients will be randomized in either a standard group (management according to current guidelines on managing patients with ACS, Copeptin will be tested, but result will not be revealed to treating personnel) or an interventional group (Copeptin testing, further management dependent on Copeptin result).

In this interventional group, patients with a negative baseline Copeptin will be discharged into the ambulant care of co-operating resident cardiologists. Patients with a positive Copeptin result will be treated as by standard care (like patients in the control group).

The investigators will assess the efficacy and safety of the new process as compared to the standard process. Secondary endpoints will assess patient satisfaction and length of hospital stay. This study design will not only assess the diagnostic use but also the clinical relevance of Copeptin testing in the ED/CPU.

Consecutive N-STEACS patients of the Chest Pain Unit with a negative Troponin I at admission will be invited to participate. Troponin I is tested as part of the standard management of patients with suspected acute coronary syndrome on a point of care test device (POCT).

Patients who give their written informed consent will then be randomized into one of two study arms (experimental and standard management) where further management depends on their Copeptin result at admission.