Clinical trial NCT01498731: Effect of the Biomarker Copeptin in Managing Patients With Suspected Acute Coronary Syndrome (ACS)
Official title: The Effect of Integrating the Biomarker Copeptin Into the Process of Managing Patients With Suspected ACS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myocardial Infarction
Keywords: Copeptin
Troponin
Acute Coronary Syndrome
Rule-out of acute myocardial infarction
Emergency Medicine
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Kerckhoff Klinik
name: Heidelberg University
name: Universitätsklinikum Hamburg-Eppendorf
name: Wilhelminenspital Vienna
name: University Hospital, Basel, Switzerland
First posted: 2011-12-23
Enrollment: 902
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 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

Primary outcomes:
measure: Rate of major adverse cardiac events (MACE) within 30 days Copeptin vs. Control arm.
timeFrame: 30 days after discharge
Secondary outcomes:
measure: Proportion of patients in whom coronary angiography (CA) is performed Copeptin vs. Control arm.
timeFrame: within 30 days after discharge
measure: Rate of ALL major adverse cardiac events (MACE)
timeFrame: 90 days after discharge
measure: Patient satisfaction regarding management within the ED/CPU
timeFrame: no specific time frame, before discharge
measure: Length of hospital stay
timeFrame: within 30 days after discharge
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Wilhelminenspital Vienna
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: Charité - Universitätsmedizin Berlin, Berlin, Germany
name: Martin Möckel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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