Multicentre, randomized, double-blind, prospective study on the effects of ImmunoAdSorptiOn on cardiac function in patients with Dilated CardioMyopathy (IASO-DCM): Rationale and design.
Dilated cardiomyopathy
Heart failure
IgG substitution
Immunoadsorption
Randomized controlled trial
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
02 Oct 2024
02 Oct 2024
Historique:
revised:
11
08
2024
received:
24
04
2024
accepted:
09
09
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
3
10
2024
Statut:
aheadofprint
Résumé
Pilot studies indicate that immunoadsorption with subsequent IgG substitution (IA/IgG) induces beneficial effects in patients with dilated cardiomyopathy (DCM) and heart failure. This placebo-controlled study investigates whether IA/IgG treatment enhances left ventricular (LV) systolic function as compared to a control group receiving pseudo-treatment. This multicentre, randomized, double-blind, parallel-group trial aims to include 200 patients with heart failure due to DCM (LV ejection fraction [LVEF] <40%) on optimized guideline-directed heart failure medication. Participants are randomly assigned in a 1:1 ratio to IA/IgG using protein-A columns, or to pseudo-immunoadsorption followed by an intravenous infusion without IgG. Follow-up visits take place by telephone after 1 and 3 months and at the study centres after 6, 12 and 24 months. The primary efficacy endpoint is the change in LVEF from baseline to 6 months determined by contrast echocardiography, analysed at a core lab. In addition, LV end-diastolic and end-systolic volumes will be analysed as secondary endpoints over the entire study period to assess whether IA/IgG affects LV remodelling. As main secondary outcome, a composite of all-cause death, cardiac resuscitation, hospitalization for heart failure, and need for cardiac surgery to improve myocardial pump function will be evaluated after 24 months. In addition, exploratory outcomes as well as safety endpoints related to the treatment will be assessed throughout the whole study period. IASO-DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Krupp von Bohlen und Halbach-Foundation
Organisme : ENDI-Foundation
Organisme : Fresenius Medical Care GmbH
Organisme : Bristol-Myers Squibb
Organisme : Octapharm AG
Organisme : German Centre for Cardiovascular Research
Informations de copyright
© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Références
Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales‐Villa R, Basso C, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023;44:3503–3626. https://doi.org/10.1093/eurheartj/ehad194
Heymans S, Lakdawala NK, Tschope C, Klingel K. Dilated cardiomyopathy: Causes, mechanisms, and current and future treatment approaches. Lancet 2023;402:998–1011. https://doi.org/10.1016/S0140‐6736(23)01241‐2
Merlo M, Cannatà A, Pio Loco C, Stolfo D, Barbati G, Artico J, et al. Contemporary survival trends and aetiological characterization in non‐ischaemic dilated cardiomyopathy. Eur J Heart Fail 2020;22:1111–1121. https://doi.org/10.1002/ejhf.1914
Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno‐Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2648a–2648d. https://doi.org/10.1093/eurheartj/eht210
Tschöpe C, Ammirati E, Bozkurt B, Caforio ALP, Cooper LT, Felix SB, et al. Myocarditis and inflammatory cardiomyopathy: Current evidence and future directions. Nat Rev Cardiol 2021;18:169–193. https://doi.org/10.1038/s41569‐020‐00435‐x
Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: The complexity of a diverse genetic architecture. Nat Rev Cardiol 2013;10:531–547. https://doi.org/10.1038/nrcardio.2013.105
Felix SB, Beug D, Dörr M. Immunoadsorption therapy in dilated cardiomyopathy. Expert Rev Cardiovasc Ther 2015;13:145–152. https://doi.org/10.1586/14779072.2015.990385
Dickstein K, Cohen‐Solal A, Filippatos G, McMurray J, Ponikowski P, Poole‐Wilson PA, et al.; ESC Committee for Practice Guidelines (CPG). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388–2442. https://doi.org/10.1093/eurheartj/ehn309
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al.; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129–2200. https://doi.org/10.1093/eurheartj/ehw128
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al.; Eplerenone Post‐Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309–1321. https://doi.org/10.1056/NEJMoa030207
Cheitlin MD, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davis JL, et al. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography – summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). J Am Coll Cardiol 2003;42:954–970. https://doi.org/10.1016/s0735‐1097(03)01065‐9
Groenning BA, Nilsson JC, Sondergaard L, Fritz‐Hansen T, Larsson HB, Hildebrandt PR. Antiremodeling effects on the left ventricle during beta‐blockade with metoprolol in the treatment of chronic heart failure. J Am Coll Cardiol 2000;36:2072–2080. https://doi.org/10.1016/s0735‐1097(00)01006‐8
McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre‐Amione G, et al. Controlled trial of intravenous immune globulin in recent‐onset dilated cardiomyopathy. Circulation 2001;103:2254–2259. https://doi.org/10.1161/01.cir.103.18.2254
Schultheiss HP, Kuhl U, Janda I, Melzner B, Ulrich G, Morad M. Antibody‐mediated enhancement of calcium permeability in cardiac myocytes. J Exp Med 1988;168:2105–2119. https://doi.org/10.1084/jem.168.6.2105
Baritussio A, Schiavo A, Basso C, Giordani AS, Cheng CY, Pontara E, et al. Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: Negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies. Eur J Heart Fail 2022;24:1033–1044. https://doi.org/10.1002/ejhf.2496
Felix SB, Staudt A, Landsberger M, Grosse Y, Stangl V, Spielhagen T, et al. Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption. J Am Coll Cardiol 2002;39:646–652. https://doi.org/10.1016/s0735‐1097(01)01794‐6
Staudt A, Staudt Y, Dörr M, Böhm M, Knebel F, Hummel A, et al. Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy. J Am Coll Cardiol 2004;44:829–836. https://doi.org/10.1016/j.jacc.2004.04.055
Matsui S, Fu ML, Katsuda S, Hayase M, Yamaguchi N, Teraoka K, et al. Peptides derived from cardiovascular G‐protein‐coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol 1997;29:641–655. https://doi.org/10.1006/jmcc.1996.0307
Jahns R, Boivin V, Hein L, Triebel S, Angermann CE, Ertl G, et al. Direct evidence for a beta 1‐adrenergic receptor‐directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. J Clin Invest 2004;113:1419–1429. https://doi.org/10.1172/JCI20149
Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD‐1‐deficient mice. Nat Med 2003;9:1477–1483. https://doi.org/10.1038/nm955
Caforio AL, Mahon NG, Baig MK, Tona F, Murphy RT, Elliott PM, et al. Prospective familial assessment in dilated cardiomyopathy: Cardiac autoantibodies predict disease development in asymptomatic relatives. Circulation 2007;115:76–83. https://doi.org/10.1161/CIRCULATIONAHA.106.641472
Felix SB, Staudt A, Dörffel WV, Stangl V, Merkel K, Pohl M, et al. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: Three‐month results from a randomized study. J Am Coll Cardiol 2000;35:1590–1598. https://doi.org/10.1016/s0735‐1097(00)00568‐4
Staudt A, Schäper F, Stangl V, Plagemann A, Böhm M, Merkel K, et al. Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution. Circulation 2001;103:2681–2686. https://doi.org/10.1161/01.cir.103.22.2681
Müller J, Wallukat G, Dandel M, Bieda H, Brandes K, Spiegelsberger S, et al. Immunoglobulin adsorption in patients with idiopathic dilated cardiomyopathy. Circulation 2000;101:385–391. https://doi.org/10.1161/01.cir.101.4.385
Staudt A, Böhm M, Knebel F, Grosse Y, Bischoff C, Hummel A, et al. Potential role of autoantibodies belonging to the immunoglobulin G‐3 subclass in cardiac dysfunction among patients with dilated cardiomyopathy. Circulation 2002;106:2448–2453. https://doi.org/10.1161/01.cir.0000036746.49449.64
Ameling S, Herda LR, Hammer E, Steil L, Teumer A, Trimpert C, et al. Myocardial gene expression profiles and cardiodepressant autoantibodies predict response of patients with dilated cardiomyopathy to immunoadsorption therapy. Eur Heart J 2013;34:666–675. https://doi.org/10.1093/eurheartj/ehs330
Staudt A, Dörr M, Staudt Y, Böhm M, Probst M, Empen K, et al. Role of immunoglobulin G3 subclass in dilated cardiomyopathy: Results from protein A immunoadsorption. Am Heart J 2005;150:729–736. https://doi.org/10.1016/j.ahj.2004.11.002
Staudt A, Hummel A, Ruppert J, Dörr M, Trimpert C, Birkenmeier K, et al. Immunoadsorption in dilated cardiomyopathy: 6‐month results from a randomized study. Am Heart J 2006;152:712.e1–712.e6. https://doi.org/10.1016/j.ahj.2006.06.027
Bristow MR, Kao DP, Breathett KK, Altman NL, Gorcsan J III, Gill EA, et al. Structural and functional phenotyping of the failing heart: Is the left ventricular ejection fraction obsolete? JACC Heart Fail 2017;5:772–781. https://doi.org/10.1016/j.jchf.2017.09.009
Abboud A, Januzzi JL. Reverse cardiac remodeling and ARNI therapy. Curr Heart Fail Rep 2021;18:71–83. https://doi.org/10.1007/s11897‐021‐00501‐6
Hoffmann R, von Bardeleben S, ten Cate F, Borges AC, Kasprzak J, Firschke C, et al. Assessment of systolic left ventricular function: A multi‐centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast‐enhanced echocardiography. Eur Heart J 2005;26:607–616. https://doi.org/10.1093/eurheartj/ehi083