Multicentre, randomized, double-blind, prospective study on the effects of ImmunoAdSorptiOn on cardiac function in patients with Dilated CardioMyopathy (IASO-DCM): Rationale and design

Abstract

Aims: 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.

Methods: 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.

Conclusion: IASO-DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM.

Keywords: Dilated cardiomyopathy; Heart failure; IgG substitution; Immunoadsorption; Randomized controlled trial.

Figure 1

Study interventions. Protein A immunoadsorption is a technique that selectively removes antibodies from blood by exploiting the high affinity of protein A, derived from Staphylococcus aureus, for the Fc region of IgG antibodies. In this method, protein A is immobilized on a solid matrix, such as Agarose or Sepharose beads, creating an immunoadsorbent column. For this purpose, blood is first separated into plasma and cell components in a plasma separator. When the biological fluid is passed through the column, IgG antibodies bind specifically to protein A. The column is then washed to remove unbound substances, and the bound antibodies are eluted using a buffer that disrupts the protein A–IgG interaction. Plasma and cell components are then returned to the patient. In the study, the passage through the columns is omitted in the control group. In addition, IgG (verum group) or saline (control group) is substituted after the last treatment session as part of the study.

Figure 2

Study flow‐chart. Overview of the study design, study visits and study measures in both study groups. CRP, C‐reactive protein; ECG, electrocardiogram; hs, high‐sensitivity; IA, immunoadsorption; ICD, implantable cardiac defibrillator; IgG/G3/A/M, immunoglobulin G/G3/A/M; IL‐6, interleukin‐6; MLHFQ, Minnesota Living with Heart Failure Questionnaire; MRI, magnetic resonance imaging; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.