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

NCT01498731 | Completed

• 3 other identifiers: Charite-BiC-8DRKS00000276U1111-1118-1665
• Study Type: interventional
• Target: 902
• Locations: 3 countries
• Sites: 6

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.

Conditions

Acute Myocardial Infarction

Keywords

Copeptin; Troponin; Acute Coronary Syndrome; Rule-out of acute myocardial infarction; Emergency Medicine

Outcome Measures

Primary Outcomes (1)

• Rate of major adverse cardiac events (MACE) within 30 days Copeptin vs. Control arm.

  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).

  30 days after discharge

Secondary Outcomes (4)

• Proportion of patients in whom coronary angiography (CA) is performed Copeptin vs. Control arm.

  within 30 days after discharge

• Rate of ALL major adverse cardiac events (MACE)

  90 days after discharge

• Patient satisfaction regarding management within the ED/CPU

  no specific time frame, before discharge

• Length of hospital stay

  within 30 days after discharge

Study Arms (2)

Copeptin

EXPERIMENTAL

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

Standard

NO INTERVENTION

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.

Interventions

Discharge home BEHAVIORAL

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.

Copeptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Kerckhoff Klinik: collaborator
• Heidelberg University: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Wilhelminenspital Vienna: collaborator
• University Hospital, Basel, Switzerland: collaborator

Study Sites (6)

Wilhelminenspital Vienna

Vienna, 1160, Austria

Location

Kerckhoff-Klinik GmbH

Bad Nauheim, 61231, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (14)

• Mockel M, Muller R, Vollert J, Muller C, Danne O, Gareis R, Stork T, Dietz R, Koenig W. Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II). Clin Res Cardiol. 2007 Sep;96(9):604-12. doi: 10.1007/s00392-007-0540-x. Epub 2007 Jun 27.

  PMID: 17593313 BACKGROUND

• Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J. 2007 Oct;28(20):2525-38. doi: 10.1093/eurheartj/ehm355. No abstract available.

  PMID: 17951287 BACKGROUND

• Newby LK, Storrow AB, Gibler WB, Garvey JL, Tucker JF, Kaplan AL, Schreiber DH, Tuttle RH, McNulty SE, Ohman EM. Bedside multimarker testing for risk stratification in chest pain units: The chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I (CHECKMATE) study. Circulation. 2001 Apr 10;103(14):1832-7. doi: 10.1161/01.cir.103.14.1832.

  PMID: 11294799 BACKGROUND

• Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, Griffith JL, Selker HP. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med. 2000 Apr 20;342(16):1163-70. doi: 10.1056/NEJM200004203421603.

  PMID: 10770981 BACKGROUND

• Itoi K, Jiang YQ, Iwasaki Y, Watson SJ. Regulatory mechanisms of corticotropin-releasing hormone and vasopressin gene expression in the hypothalamus. J Neuroendocrinol. 2004 Apr;16(4):348-55. doi: 10.1111/j.0953-8194.2004.01172.x.

  PMID: 15089973 BACKGROUND

• Katan M, Morgenthaler N, Widmer I, Puder JJ, Konig C, Muller B, Christ-Crain M. Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. Neuro Endocrinol Lett. 2008 Jun;29(3):341-6.

  PMID: 18580851 BACKGROUND

• Khan SQ, Dhillon OS, O'Brien RJ, Struck J, Quinn PA, Morgenthaler NG, Squire IB, Davies JE, Bergmann A, Ng LL. C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study. Circulation. 2007 Apr 24;115(16):2103-10. doi: 10.1161/CIRCULATIONAHA.106.685503. Epub 2007 Apr 9.

  PMID: 17420344 BACKGROUND

• Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-8. doi: 10.1016/j.jacc.2009.01.076.

  PMID: 19555842 BACKGROUND

• Voors AA, von Haehling S, Anker SD, Hillege HL, Struck J, Hartmann O, Bergmann A, Squire I, van Veldhuisen DJ, Dickstein K; OPTIMAAL Investigators. C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: results from the OPTIMAAL study. Eur Heart J. 2009 May;30(10):1187-94. doi: 10.1093/eurheartj/ehp098. Epub 2009 Apr 3.

  PMID: 19346228 BACKGROUND

• Keller T, Tzikas S, Zeller T, Czyz E, Lillpopp L, Ojeda FM, Roth A, Bickel C, Baldus S, Sinning CR, Wild PS, Lubos E, Peetz D, Kunde J, Hartmann O, Bergmann A, Post F, Lackner KJ, Genth-Zotz S, Nicaud V, Tiret L, Munzel TF, Blankenberg S. Copeptin improves early diagnosis of acute myocardial infarction. J Am Coll Cardiol. 2010 May 11;55(19):2096-106. doi: 10.1016/j.jacc.2010.01.029.

  PMID: 20447532 BACKGROUND

• Morgenthaler NG, Struck J, Alonso C, Bergmann A. Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2006 Jan;52(1):112-9. doi: 10.1373/clinchem.2005.060038. Epub 2005 Nov 3.

  PMID: 16269513 BACKGROUND

• Giannitsis E, Kehayova T, Vafaie M, Katus HA. Combined testing of high-sensitivity troponin T and copeptin on presentation at prespecified cutoffs improves rapid rule-out of non-ST-segment elevation myocardial infarction. Clin Chem. 2011 Oct;57(10):1452-5. doi: 10.1373/clinchem.2010.161265. Epub 2011 Aug 1.

  PMID: 21807867 BACKGROUND

• Giannitsis E, Garfias-Veitl T, Slagman A, Searle J, Muller C, Blankenberg S, von Haehling S, Katus HA, Hamm CW, Huber K, Vollert JO, Mockel M. Biomarkers-in-Cardiology 8 RE-VISITED-Consistent Safety of Early Discharge with a Dual Marker Strategy Combining a Normal hs-cTnT with a Normal Copeptin in Low-to-Intermediate Risk Patients with Suspected Acute Coronary Syndrome-A Secondary Analysis of the Randomized Biomarkers-in-Cardiology 8 Trial. Cells. 2022 Jan 8;11(2):211. doi: 10.3390/cells11020211.

  PMID: 35053326 DERIVED

• Reinhold T, Giannitsis E, Mockel M, Frankenstein L, Vafaie M, Vollert JO, Slagman A. Cost analysis of early discharge using combined copeptin/cardiac troponin testing versus serial cardiac troponin testing in patients with suspected acute coronary syndrome. PLoS One. 2018 Aug 23;13(8):e0202133. doi: 10.1371/journal.pone.0202133. eCollection 2018.

  PMID: 30138394 DERIVED

MeSH Terms

Conditions

Diabetes Insipidus; Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Martin Möckel, MD, PhD

  Charité - Universitätsmedizin Berlin, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Emergency Medicine

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: December 23, 2011
• Study Start: April 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

AU (1); DE (4); CH (1)