Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study

NCT ID: NCT03072199

Last Updated: 2021-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2021-05-01

Brief Summary

RITA-MI aims to develop of a novel therapeutic concept to target the immune response in patients with acute myocardial infarction (MI) by depleting B-cells with a single injection of Rituximab which is approved for clinical use in cancer, autoimmune disease and inflammatory conditions. The goal is to re-purpose the drug, and translate the discovery into benefit for patients at high risk of cardiovascular events. Rituximab is expected to limit infarction size and improve the healing process, as complementary to other therapeutic strategies.

The applicants intend to perform a clinical study in patients with acute myocardial infarction (MI). The objective is to find the optimal dose (lowest dose with highest biological efficacy and best safety profile) for peripheral blood B cell depletion during the first 6 days after injection, and selective molecular signatures associated with improved heart function through analysis of peripheral blood samples.

The study rationale is to decrease the inflammatory reaction upon tissue necrosis following heart muscle ischemia.

Conditions

Ischemic Heart Disease; Myocardial Infarction; Inflammation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Group Type: EXPERIMENTAL

RiTUXimab Injection

Intervention Type: DRUG

Single dose of Rituximab given intravenously within 48hours of myocardial infarction

Interventions

RiTUXimab Injection

Single dose of Rituximab given intravenously within 48hours of myocardial infarction

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18-75 years old
• Acute anterior (left anterior descending artery) STEMI and successful primary percutaneous coronary intervention (PCI) with stent implantation in the culprit lesion during the first 24h after onset of symptoms

Exclusion Criteria

• A previous history of STEMI
• Cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability or severe congestive heart failure
• Residual severe proximal bystander disease awaiting inpatient revascularisation
• Corrected QT interval (QTc) > 500 msecs using Bazett's formula
• Hematologic abnormalities (hemoglobin <10 g/dL or hematocrit <30%, platelet cell count of <100 x103/μL, white blood cell count <4 x103/μL)
• Hypogammaglobulinaemia (defined as <3g/L of IgG)
• Renal failure (estimated GFR by the MDRD formula < 45 ml/min/1.73m2);
• Known hepatic failure or abnormal liver function tests at baseline (ALT > 2 x ULN).
• Active or recurrent hepatitis (type B).
• Known HIV infection
• Current or previous tuberculosis (Chest X-Ray)
• Current infections
• Presence or history in the previous five years of an ongoing cancer, except in situ cancer of the cervix or basal cell carcinoma
• Any oral or intravenous immunosuppressive treatment (other than concomitant 100 mg methylprednisolone), disease modifying drugs, or other immune modulatory monoclonal antibodies or immunodepleting therapy at any time
• Allergy to rituximab or one of its excipients
• Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses.
• Known or suspected pregnancy at screening or lactating woman
• Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post-menopausal
• Participation in other clinical trials
• Inability to comply with study procedures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Papworth Hospital NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Papworth Hospital NHS Trust

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

References

Zhao TX, Aetesam-Ur-Rahman M, Sage AP, Victor S, Kurian R, Fielding S, Ait-Oufella H, Chiu YD, Binder CJ, Mckie M, Hoole SP, Mallat Z. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study. Cardiovasc Res. 2022 Feb 21;118(3):872-882. doi: 10.1093/cvr/cvab113.

Reference Type: DERIVED

PMID: 33783498 (View on PubMed)

Other Identifiers

P02100

Identifier Type: -

Identifier Source: org_study_id