Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction
Primary Purpose
Heart Failure, Coronary Heart Disease
Status
Withdrawn
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Immunoadsorption / Immunoglobulin substitution
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring heart failure, coronary heart disease, autoantibodies, immunoadsorption, 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
Sites / Locations
- Ernst-Moritz-Arndt-Universität
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
1
2
Arm Description
Immunoadsorption with subsequent immunoglobulin substitution
Outcomes
Primary Outcome Measures
left-ventricular ejection fraction as measured by echocardiography
Secondary Outcome Measures
cardiac index
systemic vascular resistance
pulmonary vascular resistance
n-terminal pro-BNP concentration (serum)
peak oxygen uptake (spiroergometric)
dyspnoea symptoms / NYHA classification
Full Information
NCT ID
NCT00738517
First Posted
August 18, 2008
Last Updated
May 10, 2016
Sponsor
University Medicine Greifswald
Collaborators
Fresenius Medical Care North America
1. Study Identification
Unique Protocol Identification Number
NCT00738517
Brief Title
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
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Withdrawn
Why Stopped
PI left center
Study Start Date
September 2008 (undefined)
Primary Completion Date
June 2011 (Anticipated)
Study Completion Date
December 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University Medicine Greifswald
Collaborators
Fresenius Medical Care North America
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Coronary Heart Disease
Keywords
heart failure, coronary heart disease, autoantibodies, immunoadsorption, immunoglobulin substitution
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Immunoadsorption with subsequent immunoglobulin substitution
Arm Title
2
Arm Type
No Intervention
Intervention Type
Device
Intervention Name(s)
Immunoadsorption / Immunoglobulin substitution
Other Intervention Name(s)
Immunosorba
Intervention Description
Immunoadsorption with protein-A columns on five consecutive days with subsequent human polyclonal immunoglobulin G substitution after day 5 (0,5g /kg bodyweight)
Primary Outcome Measure Information:
Title
left-ventricular ejection fraction as measured by echocardiography
Time Frame
6 months
Secondary Outcome Measure Information:
Title
cardiac index
Time Frame
6 months
Title
systemic vascular resistance
Time Frame
6 months
Title
pulmonary vascular resistance
Time Frame
6 months
Title
n-terminal pro-BNP concentration (serum)
Time Frame
6 months
Title
peak oxygen uptake (spiroergometric)
Time Frame
6 months
Title
dyspnoea symptoms / NYHA classification
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan B Felix, MD
Organizational Affiliation
University Medicine Greifswald
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lars R Herda, MD
Organizational Affiliation
University Medicine Greifswald
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Astrid Hummel, MD
Organizational Affiliation
University Medicine Greifswald
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marcus Doerr, MD
Organizational Affiliation
University Medicine Greifswald
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daniel Beug, MD
Organizational Affiliation
University Medicine Greifswald
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ernst-Moritz-Arndt-Universität
City
Greifswald
State/Province
MV
ZIP/Postal Code
17475
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
9950662
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.
Results Reference
background
PubMed Identifier
14595408
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.
Results Reference
background
PubMed Identifier
9133505
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.
Results Reference
background
PubMed Identifier
10807465
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.
Results Reference
background
PubMed Identifier
11390337
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.
Results Reference
background
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Immunoadsorption and Immunoglobulin Substitution for Heart Failure After Myocardial Infarction
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