Rituximab in Patients With ST-elevation Myocardial Infarction

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The main objective is to compare the effect of a single injection of two doses of rituximab versus placebo on 6 months left ventricular systolic function, using CMR, in patients who have had an acute anterior STEMI.

The primary endpoint is the left ventricular ejection fraction (LVEF) by CMR at 6 months.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Institut National de la Santé Et de la Recherche Médicale, France

Criteria

Inclusion Criteria:

Inclusion Criteria :

• Age 18-75 (women must be either postmenopausal defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate (>55 years old), history of vasomotor symptoms) or having documented hysterectomy and/or bilateral oophorectomy) ;

• Clinical evidence at presentation of anterior ST-elevation myocardial infarction (STEMI) defined as symptoms suggestive of acute myocardial ischemia, an electrocardiogram showing ST-segment elevation ≥2 mm in ≥2 contiguous leads in V1 to V4;

• Complete occlusion (i.e. TIMI flow 0-1) of proximal or mid left anterior descending (LAD) coronary artery on urgent angiography interpreted as the infarct-related artery (IRA);

• Onset of worse symptoms within 6 hours before admission;

• Plan to provide primary percutaneous angioplasty (PPCI) for the patient within 2 hours of ECG diagnosis;

• Ability to start infusion of rituximab within 3 hours of PPCI ;

• Written informed consent.

Exclusion Criteria:

• History of previous MI;

• Presentation with cardiac arrest;

• Cardiogenic shock (defined as systolic blood pressure <90 mmHg for >30minutes, or necessitating vasopressors to achieve a blood pressure ≥90 mmHg);

• Cardiac electrical instability (defined as complete heart block needing temporary pacing or any tachyarrhythmia needing cardioversion);

• Patients with Killip class III heart failure;

• History of severe chronic renal failure (define as stage 4 (GFR = 15-29 mL/min) or worse);

• History of hepatitis B, HIV or tuberculosis;

• Patient positive for point of care bedside test of Ag HBs;

• Severe, progressive infections documented;

• Active COVID-19 infection or COVID-19 infection within 3 months;

• Patient with documented severe immune deficiency;

• Presence, or history in ≤ five years, of an ongoing cancer, (except in situ cancer of the cervix or basal cell carcinoma);

• QTcF> 450 msecs in males, > 470msecs in females;

• Any oral or intravenous immunosuppressive treatment, immune modulatory monoclonal antibodies or immunodepleting therapy at any time (inhalers and topical creams with corticosteroids are permitted);

• Previous history of major organ transplant including renal transplant;

• Known hypersensitivity to the active substance of MabThera® (rituximab) or to proteins of murine origin, or to any of the other excipients;

• Any contraindications to any of the Mabthera® premedication drugs;

• Contraindications to injectable Polaramine :

Risk of closed-angle glaucoma, Risk of urinary retention linked to urethro-prostatic disorders;

• Expected need for vaccination with a live attenuated vaccine during the study, including incomplete vaccination courses (in case, life, attenuated vaccine must be administered at least 30 days before inclusion in study);

• Absence of COVID-19 vaccination (with 2 doses of COVID-19 vaccination or patient infected with COVID-19 and whom received one dose of COVID-19 vaccination);

• Any obvious contraindications for MRI or conditions which will impede image acquisition for example:

• Severe claustrophobia

• Non-MRI compatible permanent pacemaker

• Patients who have a metallic foreign body (metal silver) in their eye, or who have an aneurysm clip in their brain

• Patients who have had metallic devices placed in their back

• Known hypersensitivity to imaging products (gadoteric acid, meglumin or any drug containing gadolinium)

• Known hepatic failure;

• Previous history of progressive multifocal leukoencephalopathy;

• Inclusion in other interventional drug study within the previous 3 months;

• Inability to comply with study procedures;

• Patients under guardianship or curatorship.