Clinical trial NCT00738517: Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction
Official title: Immunoadsorption With Subsequent Immunoglobulin Substitution for Patients With Heart Failure After Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Coronary Heart Disease
Keywords: heart failure
coronary heart disease
autoantibodies
immunoadsorption
immunoglobulin substitution
Lead sponsor: University Medicine Greifswald
Sponsor class: OTHER
Collaborators: name: Fresenius Medical Care North America
First posted: 2008-08-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: left-ventricular ejection fraction as measured by echocardiography
timeFrame: 6 months
Secondary outcomes:
measure: cardiac index
timeFrame: 6 months
measure: systemic vascular resistance
timeFrame: 6 months
measure: pulmonary vascular resistance
timeFrame: 6 months
measure: n-terminal pro-BNP concentration (serum)
timeFrame: 6 months
measure: peak oxygen uptake (spiroergometric)
timeFrame: 6 months
measure: dyspnoea symptoms / NYHA classification
timeFrame: 6 months
Other outcomes:
Locations:
city: Greifswald
country: Germany
facility: Ernst-Moritz-Arndt-Universität
state: MV
Study officials:
affiliation: University Medicine Greifswald
name: Stephan B Felix, MD
role: STUDY_CHAIR
affiliation: University Medicine Greifswald
name: Lars R Herda, MD
role: STUDY_DIRECTOR
affiliation: University Medicine Greifswald
name: Astrid Hummel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medicine Greifswald
name: Marcus Doerr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medicine Greifswald
name: Daniel Beug, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1161/01.cir.99.5.649.
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. doi: 10.1038/nm955. Epub 2003 Nov 2.
citation: 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.
citation: 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.
citation: 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.