Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction

Immunoadsorption With Subsequent Immunoglobulin Substitution for Patients With Heart Failure After Myocardial Infarction

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.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure; Coronary Heart Disease
• Intervention / Treatment: Device: Immunoadsorption / Immunoglobulin substitution

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • MV
    • Greifswald, MV, Germany, 17475
      • Ernst-Moritz-Arndt-Universität

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 2
Active Comparator: 1; Immunoadsorption with subsequent immunoglobulin substitution	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); Other Names: Immunosorba

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
left-ventricular ejection fraction as measured by echocardiography	6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Medicine Greifswald
• Collaborators: Fresenius Medical Care North America
• Investigators: Study Chair: Stephan B Felix, MD, University Medicine Greifswald; Study Director: Lars R Herda, MD, University Medicine Greifswald; Principal Investigator: Astrid Hummel, MD, University Medicine Greifswald; Principal Investigator: Marcus Doerr, MD, University Medicine Greifswald; Principal Investigator: Daniel Beug, MD, University Medicine Greifswald

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: August 18, 2008
• First Submitted That Met QC Criteria: August 18, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Estimate): May 11, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: heart failure; autoantibodies; coronary heart disease; immunoadsorption; immunoglobulin substitution
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Infarction; Infarction; Heart Failure; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: MPG 01/08