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

This study has been completed.
Sponsor:
Collaborators:
Kerckhoff-Klinik Bad Nauheim
Heidelberg University
Universitätsklinikum Hamburg-Eppendorf
Wilhelminenspital Vienna
University Hospital, Basel, Switzerland
Information provided by (Responsible Party):
Martin Moeckel, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01498731
First received: October 25, 2011
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

Acute chest pain is commonly known to be the classic symptom of acute myocardial infarction. Of the many patients which visit the Emergency Department because of chest pain, less than half do actually suffer from an acute myocardial infarction or acute myocardial ischemia. In some patients the acute myocardial infarction can be diagnosed at admission, either because of typical changes in their ECG (STEMI, ST-elevation myocardial infarction)or because of increased levels of the laboratory value Troponin in their blood (NSTEMI, Non-ST-elevation myocardial infarction). Troponin is currently the most important marker to diagnose acute myocardial infarction. Unfortunately a lot of patients with suspected acute coronary syndrome do not show any ECG or Troponin changes. These patients pose a major problem in emergency medicine as they need to precautionally be admitted to a chest pain unit and to be started on medical treatment until a second Troponin test after 6-9 hours is available.

In this study, we investigate the biomarker Copeptin. Copeptin has shown excellent results in diagnostic clinical trials assessing its use in various acute diseases. There are three important trials showing an excellent negative predictive value of Copeptin in combination with Troponin in patients with suspected acute coronary syndrome (Reichlin et al., JACC, 2009; Keller et al. JACC, 2010, Giannitsis et al. Clin Chem 2011).

This trial compares two processes of managing patients with suspected acute coronary syndrome (ACS), the standard process according to current guidelines and the experimental process integrating copeptin as a rule-out marker for acute myocardial infarction into management decisions. Main Hypothesis: Patients with suspected ACS who test negative for Troponin and negative for Copeptin at their initial presentation to the ED can safely be discharged (interventional process). They will not experience more major cardiac adverse events than patients who were managed by standard practise (control process)within 30 days after admission.

The Investigators want to test Copeptin in patients with suspected acute coronary syndrome in whom the ECG is unspecific and the initial Troponin test is negative. Further patient care will be based on the Copeptin result. Patients with a negative Copeptin will be discharged into the ambulant care of resident cardiologists.Copeptin positive patients will be managed according to standard guidelines for the management of patients with ACS.


Condition Intervention
Acute Myocardial Infarction
Behavioral: Discharge home

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Effect of Integrating the Biomarker Copeptin Into the Process of Managing Patients With Suspected ACS

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Enrollment: 902
Study Start Date: April 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copeptin

Patients who test negative for Copeptin at admission will be considered low-risk and will be discharged home without further interventions.

To secure the patients safety they will be transferred into our co-operating network of resident cardiologists using the software "Praxis-connect" i.e. these patients will be discharged with an electronically booked appointment to see a cardiologist preferably the next day (but latest within the next three days). In case of any findings suggestive of acute coronary syndrome or worsening of the patient's condition, the patient will immediately be re-admitted to our Emergency Room.

Patients who test positive for Copeptin will be treated as by standard practise.

Behavioral: Discharge home
Patients who test negative for Copeptin at admission will be considered low-risk and will be discharged home. To secure the patients safety they will be transferred into our co-operating network of resident cardiologists preferably the next day (but latest within the next three days). In case of any findings suggestive of acute coronary syndrome or worsening of the patient's condition, the patient will immediately be re-admitted to our Emergency Room.
No Intervention: Standard
Patients will be managed as by standard practice abiding current guidelines for the management of patients with suspected ACS.The copeptin result will not be available for the treating physician.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Typical chest pain (with or without ECG-changes, but no ST-elevation)suggestive of unstable angina or non-ST-elevated myocardial infarction (NSTEMI)
  • Troponin negative at admission according to the current clinical practice Patient willing and able to give written informed consent

Exclusion Criteria:

  • Patients with ST-elevation myocardial infarction (STEMI)
  • Continuing chest pain or recurrent episodes of chest pain under therapy
  • High-risk patients with suspected ACS who need to be hospitalized for reasons independent of their initial troponin result
  • Patients who need to be hospitalized for other medical reasons
  • Patients in need of urgent life-saving interventions
  • Patients under 18 years of age
  • Patients with a life expectancy < 6 months
  • Patients with any condition that leads the treating physician to not consider the patient eligible for the trial
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01498731

Locations
Austria
Wilhelminenspital Vienna
Vienna, Austria, 1160
Germany
Kerckhoff-Klinik GmbH
Bad Nauheim, Germany, 61231
Charité - Universitätsmedizin Berlin
Berlin, Germany, 13353
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Switzerland
University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
Charite University, Berlin, Germany
Kerckhoff-Klinik Bad Nauheim
Heidelberg University
Universitätsklinikum Hamburg-Eppendorf
Wilhelminenspital Vienna
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Martin Möckel, MD, PhD Charité - Universitätsmedizin Berlin, Berlin, Germany
  More Information

Additional Information:
Publications:

Responsible Party: Martin Moeckel, Head Emergency Medicine, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01498731     History of Changes
Other Study ID Numbers: Charite-BiC-8, DRKS00000276, U1111-1118-1665
Study First Received: October 25, 2011
Last Updated: June 4, 2013
Health Authority: Germany: Ministry of Health

Keywords provided by Charite University, Berlin, Germany:
Copeptin
Troponin
Acute Coronary Syndrome
Rule-out of acute myocardial infarction
Emergency Medicine

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on July 26, 2014