Rituximab in patients with acute myocardial infarction: a phase 2 placebo-controlled randomised clinical trial

RITA-MI 2 will assess the impact of a novel therapeutic strategy targeting patients immune response on the recovery of heart function after myocardial infarction (MI) in a phase 2 clinical trial.Cardiovascular diseases (CVD) represent a major cause of morbidity and mortality worldwide.

Despite important advances in the treatment of acute MI, the occurrence of MI still results in left ventricular dysfunction in up to 50% of patients, which leads to the development of heart failure.

Left ventricular dysfunction is the strongest predictor of adverse outcome after acute MI, and is associated with a 3 to 4-fold increase in mortality risk.

In Westernised countries, heart failure is responsible for 1-2% of all health expenditure, which is mostly driven by repeated hospital admissions.

Therefore, there is a considerable need for new therapies to limit the burden of CVD.This application builds on a ground-breaking discovery by a unique team of clinicians and scientists who provided extensive validation for their findings through a series of basic, pre-clinical and translational research.

Our goal is to translate this discovery into benefit for patients.

The new therapy is based on selective targeting of a specific immune cell subset, mature B lymphocytes, with the aim to limit deleterious cardiac remodelling and improve heart function recovery post-MI.

Of note, the drug that targets this pathway, i.e., CD20 monoclonal antibody (mAb) rituximab, is available for testing in a re-purposing scheme, allowing for rapid initiation of proof-of-concept clinical trials.

The PIs of the present proposal have successfully completed a phase 1/2a clinical trial (RITA-MI, NCT03072199), which established the safety of rituximab treatment at the acute phase of MI.RITA-MI 2 will conduct a phase 2b randomised double-blind placebo-controlled CT to assess the impact of B cell depletion with the CD20 mAb rituximab on left ventricular dysfunction and cardiac remodelling after acute MI.