Rituximab in Patients With ST-elevation Myocardial Infarction: A Phase 2 Placebo-controlled Randomized Clinical Trial: RITA-MI 2
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 372
- 试验地点
- 2
- 主要终点
- Left ventricular ejection fraction (LVEF) by CMR at 6 months.
研究概览
简要总结
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. Following the sponsor's decision to stop enrolment in the 200 mg arm, the primary objective of the study is to evaluate the efficacy of a single 1000 mg dose of rituximab versus placebo.
The primary endpoint is the left ventricular ejection fraction (LVEF) by CMR at 6 months.
详细描述
RITA-MI 2 is an european phase IIb, multi-center, randomized, parallel, double-blind, placebo-controlled, clinical trial to assess the impact of B cell depletion with the CD20 mAb rituximab (1000mg) on left ventricular dysfunction and cardiac remodelling after acute MI.
Sample size :
372 patients, 1:1 ratio
Assessement:
Patients will be recruited immediately after admission for MI. The aim is to start the infusion of IMP within 3 hours of PPCI (defined as first balloon inflation).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years with no upper limit (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 or a large inferior MI with evidence of low-ejection fraction (LVEF<45%);
- •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 48 hours before primary PCI;
- •Patients with neutrophils >1.5 x 109/L at the moment of admission
- •Patients with platelet counts >75 x 109 /L at the moment of admission
- •Plan to provide primary percutaneous angioplasty (PPCI) for the patient within 2 hours of ECG diagnosis; confirmed before enrollment;
- •Ability to start infusion of rituximab within 3 hours of PPCI ; confirmed before enrollment;
- •Written informed consent.
排除标准
- •Exclusion Criteria :
- •History of previous MI without documented preserved left ventricular ejection fraction (LVEF >50%) prior to the current admission will be an exclusion criterion;
- •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 rituximab or to proteins of murine origin, or to any of the other excipients;
- •Any contraindications to any of the rituximab 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 a complete COVID-19 vaccination scheme (including recovery from documented COVID infection) as approved at the time of enrollment in the country where the patient is recruited;
- •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.
研究组 & 干预措施
Active arm 1000 mg
Active arm 1000 mg: 1 bag containing 1000 mg of rituximab* in 500 ml of NaCl 0.9% * Mabthera® and all registered biosimilars are likely to be used in this trial.
干预措施: Active arm 1000 mg (Drug)
Placebo arm
1 bag of 500 ml of NaCl 0.9%
干预措施: Placebo arm (Drug)
结局指标
主要结局
Left ventricular ejection fraction (LVEF) by CMR at 6 months.
时间窗: 6 months
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.
次要结局
- Oedema extension by CMR(At day 5 (+/-2))
- Microvascular obstruction by CMR(At day 5 (+/-2))
- T2 relaxation time at ischemic region by CMR(At day 5 (+/-2))
- NT-pro-BNP(At 6 months)
- Adverse event related to treatment(Until 12 months)
- Infarct size by CMR(At day 5 (+/-2) and at 6 months)