Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00738517
• Other study ID #: MPG 01/08
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: August 18, 2008
• Last updated: May 10, 2016
• Start date: September 2008
• Est. completion date: December 2011

Study information

• Verified date: May 2016
• Source: University Medicine Greifswald
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Heart Diseases
• Heart Failure
• Myocardial Infarction
• Myocardial Ischemia

Intervention

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)

Locations

Country	Name	City	State
Germany	Ernst-Moritz-Arndt-Universität	Greifswald	MV

Sponsors (2)

Lead Sponsor	Collaborator
University Medicine Greifswald	Fresenius Medical Care North America

Country where clinical trial is conducted

Germany, 

References & Publications (5)

Dörffel 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. — View Citation

Felix SB, Staudt A, Dörffel WV, Stangl V, Merkel K, Pohl M, Döcke 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. — View Citation

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. — View Citation

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. Epub 2003 Nov 2. — View Citation

Staudt A, Schäper F, Stangl V, Plagemann A, Böhm 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	left-ventricular ejection fraction as measured by echocardiography		6 months	No
Secondary	cardiac index		6 months	No
Secondary	systemic vascular resistance		6 months	No
Secondary	pulmonary vascular resistance		6 months	No
Secondary	n-terminal pro-BNP concentration (serum)		6 months	No
Secondary	peak oxygen uptake (spiroergometric)		6 months	No
Secondary	dyspnoea symptoms / NYHA classification		6 months	No