Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction

Overview

The purpose of this study is to investigate, if immunoadsorption of autoantibodies with subsequent substitution of immunoglobulins is able to improve cardiac function of patients with heart failure after myocardial infarction and presence of cardiac autoantibodies.

Full Title of Study: “Immunoadsorption With Subsequent Immunoglobulin Substitution for Patients With Heart Failure After Myocardial Infarction”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 2011

Detailed Description

Heart failure due to coronary heart disease (CHD) remains one of the most frequent causes of death. Left-ventricular ejection fraction < 30% is associated with a 5-year mortality > 70%. Therefore, new strategies and therapies towards treatment of heart failure are needed. Heart failure due to left ventricular dysfunction can develop in CHD beyond the area of myocardial infarction. Some of these patients develop myocardial autoantibodies, which have been shown to exert a negative inotropic effect. Their elimination by immunoadsorption has been shown to improve left ventricular function in dilatative cardiomyopathy. Immunoglobulins are substituted to minimize infection risk at a level, which has been shown not to effect cardiac function. This intervention might also ameliorate cardiac function in patients with heart failure due to other origins. This study therefore aims to evaluate the effect of immunoadsorption with subsequent immunoglobulin substitution.

Interventions

  • Device: Immunoadsorption / Immunoglobulin substitution
    • Immunoadsorption with protein-A columns on five consecutive days with subsequent human polyclonal immunoglobulin G substitution after day 5 (0,5g /kg bodyweight)

Arms, Groups and Cohorts

  • Active Comparator: 1
    • Immunoadsorption with subsequent immunoglobulin substitution
  • No Intervention: 2

Clinical Trial Outcome Measures

Primary Measures

  • left-ventricular ejection fraction as measured by echocardiography
    • Time Frame: 6 months

Secondary Measures

  • cardiac index
    • Time Frame: 6 months
  • systemic vascular resistance
    • Time Frame: 6 months
  • pulmonary vascular resistance
    • Time Frame: 6 months
  • n-terminal pro-BNP concentration (serum)
    • Time Frame: 6 months
  • peak oxygen uptake (spiroergometric)
    • Time Frame: 6 months
  • dyspnoea symptoms / NYHA classification
    • Time Frame: 6 months

Participating in This Clinical Trial

Inclusion Criteria

  • heart failure and known coronary heart disease / post myocardial infarction – completed treatment for coronary heart disease (no known hemodynamically effective stenosis in coronary vessels) – evidence of scarred myocardial tissue in low-dose stress echocardiography or myocardial scintigraphy or MRI – evidence of hypo-contractile myocardium in echocardiography or MRI outside of infarction area – at least 3 months without acute coronary syndrome or coronary intervention – left-ventricular ejection fraction by echocardiography < 45% – detection of at least one myocardial autoantibody (e.g. anti-ß1-receptor, anti-TnI, anti-KchIP2) in serum – dyspnea on exertion equivalent to NYHA II – NYHA IV – written informed consent of the patient Exclusion Criteria:

  • heart failure due to other cardiac disease (e.g. dilatative cardiomyopathy without evidence of CHD, primary valve defects > II°, toxic cardiomyopathy) – active infection – pregnancy – malign tumor disease – other secondary disease with life expectancy < 1 year – refusal by the patient

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Medicine Greifswald
  • Collaborator
    • Fresenius Medical Care North America
  • Provider of Information About this Clinical Study
    • Dr. med. L. R. Herda, Ernst-Moritz-Arndt-Universität
  • Overall Official(s)
    • Stephan B Felix, MD, Study Chair, University Medicine Greifswald
    • Lars R Herda, MD, Study Director, University Medicine Greifswald
    • Astrid Hummel, MD, Principal Investigator, University Medicine Greifswald
    • Marcus Doerr, MD, Principal Investigator, University Medicine Greifswald
    • Daniel Beug, MD, Principal Investigator, University Medicine Greifswald

References

Jahns R, Boivin V, Siegmund C, Inselmann G, Lohse MJ, Boege F. Autoantibodies activating human beta1-adrenergic receptors are associated with reduced cardiac function in chronic heart failure. Circulation. 1999 Feb 9;99(5):649-54. doi: 10.1161/01.cir.99.5.649.

Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, Honjo T. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003 Dec;9(12):1477-83. doi: 10.1038/nm955. Epub 2003 Nov 2.

Dorffel WV, Felix SB, Wallukat G, Brehme S, Bestvater K, Hofmann T, Kleber FX, Baumann G, Reinke P. Short-term hemodynamic effects of immunoadsorption in dilated cardiomyopathy. Circulation. 1997 Apr 15;95(8):1994-7. doi: 10.1161/01.cir.95.8.1994.

Felix SB, Staudt A, Dorffel WV, Stangl V, Merkel K, Pohl M, Docke WD, Morgera S, Neumayer HH, Wernecke KD, Wallukat G, Stangl K, Baumann G. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: three-month results from a randomized study. J Am Coll Cardiol. 2000 May;35(6):1590-8. doi: 10.1016/s0735-1097(00)00568-4.

Staudt A, Schaper F, Stangl V, Plagemann A, Bohm M, Merkel K, Wallukat G, Wernecke KD, Stangl K, Baumann G, Felix SB. Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution. Circulation. 2001 Jun 5;103(22):2681-6. doi: 10.1161/01.cir.103.22.2681.

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